Sickle Cell Anemia, Thalassemia
Conditions
Keywords
sickle cell disease, sickle cell anemia, L-glutamine, Sickle Cell Anemia (homozygous), Sickle ß0-Thalassemia
Brief summary
The purpose of this research is to evaluate the effects of L-glutamine as a therapy for sickle cell anemia and sickle ß0-thalassemia. as evaluated by the number of occurrences of sickle cell crises.
Detailed description
The primary purpose of this study is to evaluate the effectiveness of oral L-glutamine in the therapy of sickle cell anemia and sickle ß0-thalassemia. The secondary purpose is to assess the effect of L-glutamine frequency of hospitalizations for sickle cell pain, frequency of emergency room visits for sickle cell pain; energy and appetite levels; narcotics usage. Methodology: By site, patients will be randomized to L-glutamine or placebo in a 1:1 ratio after a 4-week screening period. Patients will undergo 48 weeks of treatment with dosing BID orally, with dose calculated according to patient weight. Patient visits will occur every 4 weeks. After 48 weeks of treatment, dose will be tapered to zero within 3 weeks. A final evaluation visit will occur 2 weeks after last dose.
Interventions
DRUGL-glutamine
Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
DRUGPlacebo
Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Sponsors
FDA Office of Orphan Products Development
Emmaus Medical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible to participate in the study, a patient must meet all of the following inclusion criteria: * Patient is at least five years of age. * Patient has been diagnosed with sickle cell anemia or sickle ß0-thalassemia (documented by hemoglobin electrophoresis). * Patient has had at least two episodes of painful crises within 12 months of the screening visit. * If the patient has been treated with an anti-sickling agent within three months of the screening visit, the therapy must have been continuous for at least three months with the intent to continue for the next 14 months. * Patient or the patient's legally authorized representative has given written informed consent. * If the patient is a female of child-bearing potential, she agrees to practice a recognized form of birth control during the course of the study.
Exclusion criteria
If the patient meets any of the following criteria, the patient must not be enrolled: * Patient has a significant medical condition that required hospitalization (other than sickle painful crisis) within two months of the screening visit. * Patient has diabetes mellitus with untreated fasting blood sugar \>115 mg/dL. * Patient has prothrombin time International Normalized Ratio (INR) \> 2.0. * Patient has serum albumin \< 3.0 g/dl. * Patient has received any blood products within three weeks of the screening visit. * Patient has a history of uncontrolled liver disease or renal insufficiency. * Patient is pregnant or lactating. * Patient has been treated with an experimental anti-sickling medication/treatment (except hydroxyurea) within 30 days of the screening visit. * Patient has been treated with an experimental drug within 30 days of the screening visit. * There are factors that would, in the judgment of the investigator, make it difficult for the patient to comply with the requirements of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Occurrences of Painful Sickle Cell Crises | From Week 0 through Week 48 (cumulative) | The mean number of painful sickle crisis through week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of L-glutamine on Alcohol Use | Weeks 0, 8,16, 24, 32, 40 and 48 | The patient's alcohol usage will be assessed at each visit. Alcohol usage will be reported at Weeks 0, 8,16, 24, 32, 40 and 48 |
| Effect of L-glutamine on Tobacco Use | Weeks 0, 8,16, 24, 32, 40 and 48 | Patient's alcohol usage will be assessed at each visit. Alcohol usage will be reported at Weeks 0, 8,16, 24, 32, 40 and 48 |
| Frequency of Hospitalizations for Sickle Cell Pain | From Week 0 through Week 48 (cumulative) | The mean number of hospitalizations through week 48 |
| Frequency of Emergency Room Visits for Sickle Cell Pain | From Week 0 through Week 48 (cumulative) | The mean number of emergency room visits through week 48 |
| The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin | Baseline, Weeks 4, 24 and 40 | Patient's hemoglobin will be collected at each visit.Change from Baseline will be reported at Weeks 4, 24 and 40. |
| The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit | Baseline, Weeks 4, 24, and 40 | Patient's hematocrit will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24 and 40 |
| The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count | Baseline, Weeks 0, 4, 24, 40 | Patient's reticulocyte count will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24 and 40 |
| Number of Participants With Narcotic Usage | Week 24, Week 48 | Analysis of narcotic usage was performed for the subset of patients with any narcotic use who completed the study. Changes in narcotic usage were determined by an independent consultant prior to database lock using morphine equivalents to determine relative use. |
| Energy Level (11-point Scale) | Collected at Week 0, 8, 16, 24, 32, 40, 48 | The patient's energy level was evaluated at each visit using an 11 point scale from 0=extremely tired to 10=extremely energetic |
| Patient Appetite (3-point Scale) | Collected at Week 0, 8, 16, 24, 32, 40, 48 | Patient's appetite level was evaluated at each visit using a 3 point scale: above average, average and below average. The parentages of patient at each visit whose appetite level was below, normal or above average were compared using CMH test (row mean scores) controlling for study center. |
| The Effect of Oral L-glutamine on Vital Signs - Pulse Rate | Baseline, Weeks 4, 24, and 48 | Patient's pulse rate will be collected at each visit, Change from Baseline will be reported at Weeks 4, 24, and 48 |
| The Effect of Oral L-glutamine on Vital Signs - Temperature | Baseline, Weeks 4, 24, and 48 | Patient's temperature will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48 |
| The Effect of Oral L-glutamine on Vital Signs - Respiration | Baseline, Weeks 4, 24, and 48 | Respiration will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48 |
| The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Weeks 0, 8,16, 24, 32, 40 and 48 | Percentage of days a patient's daily activities were interrupted due to sickle pain calculated at each visit. Day's interrupted will be reported at Weeks 0, 8,16, 24, 32, 40 and 48 |
| The Effect of Oral L-glutamine on Subjective Quality of Life | Baseline and Week 24 (or at time of discontinuation) | The subjective quality of life was evaluated using the scoring of the RAND 36-Item Health Survey Questionnaire. The subjective quality of life (Physical functioning, Physical health, Emotional problems, Energy/Fatigue, Emotional well being, Social functioning, Pain, General health) will be reported at Baseline and Week 24 (or at time of discontinuation). The range for Physical functioning, Physical health, Emotional problems, Emotional well being and Social functioning is 0-100, with a high score denotes a better quality of life. For Energy/Fatigue, Pain and General health the range is 0-100, with a lower score denotes better quality of life. |
| Effect of Oral L--glutamine on Height | Baseline, Weeks 4, 24, and 48 | Height will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48 |
| Effect of Oral L--glutamine on Weight | Baseline, Weeks 4, 24 and 48 | Weight will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48 |
| Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest | Baseline, Weeks 4, 24, and 48. | Minutes patient could walk without rest will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48. |
| Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest | Baseline, Weeks 4, 24, and 48. | Minutes patient could run without rest will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48. |
| Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest | Baseline, Weeks 4, 24, and 48. | Distance patient could walk without rest will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48. |
| Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest | Baseline, Weeks 4, 24, and 48. | Distance patient could run without rest will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48. |
| The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Baseline, Weeks 4, 24, and 48 | Patient's blood pressure will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Investigational Product L-glutamine
L-glutamine: Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams. | 33 |
| Placebo maltodextrin
Placebo: Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams. | 29 |
| Total | 62 |
Baseline characteristics
| Characteristic | Placebo | Investigational Product | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 30 Participants | 56 Participants |
| Age, Continuous | 26.5 years STANDARD_DEVIATION 9.42 | 30.5 years STANDARD_DEVIATION 10.09 | 28.6 years STANDARD_DEVIATION 13.8 |
| Region of Enrollment United States | 29 participants | 33 participants | 62 participants |
| Sex: Female, Male Female | 10 Participants | 22 Participants | 32 Participants |
| Sex: Female, Male Male | 19 Participants | 11 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 37 | 0 / 33 |
| other Total, other adverse events | 37 / 37 | 33 / 33 |
| serious Total, serious adverse events | 24 / 37 | 21 / 33 |
Outcome results
Primary
Number of Occurrences of Painful Sickle Cell Crises
The mean number of painful sickle crisis through week 48
Time frame: From Week 0 through Week 48 (cumulative)
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Investigational Product | Number of Occurrences of Painful Sickle Cell Crises | 4.5 Crisis | Standard Deviation 5.37 |
| Placebo | Number of Occurrences of Painful Sickle Cell Crises | 10.8 Crisis | Standard Deviation 18.74 |
p-value: 0.076Cochran-Mantel-Haenszel
Secondary
Effect of L-glutamine on Alcohol Use
The patient's alcohol usage will be assessed at each visit. Alcohol usage will be reported at Weeks 0, 8,16, 24, 32, 40 and 48
Time frame: Weeks 0, 8,16, 24, 32, 40 and 48
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 24 | NO - Alcohol Use | 22 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 0 | NO - Alcohol Use | 30 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 24 | YES - Alcohol Use | 0 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 8 | YES - Alcohol Use | 1 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 32 | NO - Alcohol Use | 19 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 40 | YES - Alcohol Use | 0 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 32 | YES - Alcohol Use | 0 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 16 | NO - Alcohol Use | 27 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 40 | NO - Alcohol Use | 18 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 0 | YES - Alcohol Use | 3 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 48 | NO - Alcohol Use | 17 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 16 | YES - Alcohol Use | 1 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 48 | YES - Alcohol Use | 0 Participants |
| Investigational Product | Effect of L-glutamine on Alcohol Use | Week 8 | NO - Alcohol Use | 25 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 48 | YES - Alcohol Use | 1 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 0 | YES - Alcohol Use | 2 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 0 | NO - Alcohol Use | 27 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 8 | NO - Alcohol Use | 20 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 8 | YES - Alcohol Use | 2 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 16 | NO - Alcohol Use | 20 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 16 | YES - Alcohol Use | 2 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 24 | NO - Alcohol Use | 19 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 24 | YES - Alcohol Use | 1 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 32 | NO - Alcohol Use | 13 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 32 | YES - Alcohol Use | 2 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 40 | YES - Alcohol Use | 2 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 48 | NO - Alcohol Use | 11 Participants |
| Placebo | Effect of L-glutamine on Alcohol Use | Week 40 | NO - Alcohol Use | 11 Participants |
Secondary
Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest
Distance patient could run without rest will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48.
Time frame: Baseline, Weeks 4, 24, and 48.
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest | Baseline - Distance patient could run without rest | 1059.5 feet | Standard Deviation 1688 |
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest | Change in Distance patient could run without rest at Week 4 | -31.6 feet | Standard Deviation 1054 |
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest | Change in Distance patient could run without rest at Week 24 | 215.9 feet | Standard Deviation 1411 |
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest | Change in Distance patient could run without rest at Week 48 | 13.5 feet | Standard Deviation 1677 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest | Change in Distance patient could run without rest at Week 48 | -586.7 feet | Standard Deviation 2698 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest | Baseline - Distance patient could run without rest | 1482.1 feet | Standard Deviation 2160 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest | Change in Distance patient could run without rest at Week 24 | 186.5 feet | Standard Deviation 2901 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Run Without Rest | Change in Distance patient could run without rest at Week 4 | 124.2 feet | Standard Deviation 1226 |
Secondary
Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest
Distance patient could walk without rest will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48.
Time frame: Baseline, Weeks 4, 24, and 48.
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest | Baseline - Distance patient could walk without rest | 4097.5 feet | Standard Deviation 2739 |
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest | Change in Distance patient could walk without rest at Week 4 | 41.9 feet | Standard Deviation 1976 |
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest | Change in Distance patient could walk without rest at Week 24 | 74.5 feet | Standard Deviation 2116 |
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest | Change in Distance patient could walk without rest at Week 48 | 38.8 feet | Standard Deviation 2766 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest | Change in Distance patient could walk without rest at Week 48 | -4240 feet | Standard Deviation 11782 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest | Baseline - Distance patient could walk without rest | 5680.7 feet | Standard Deviation 7695 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest | Change in Distance patient could walk without rest at Week 24 | -1719 feet | Standard Deviation 9569 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Distance Patient Could Walk Without Rest | Change in Distance patient could walk without rest at Week 4 | 302.5 feet | Standard Deviation 2022 |
Secondary
Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest
Minutes patient could run without rest will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48.
Time frame: Baseline, Weeks 4, 24, and 48.
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest | Baseline - Minutes patient could run without rest | 5.1 mins | Standard Deviation 8.9 |
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest | Change in Minutes patient could run without rest at Week 4 | -0.7 mins | Standard Deviation 4.75 |
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest | Change in Minutes patient could run without rest at Week 24 | -0.3 mins | Standard Deviation 5.17 |
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest | Change in Minutes patient could run without rest at Week 48 | -0.8 mins | Standard Deviation 5.14 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest | Change in Minutes patient could run without rest at Week 48 | -1.2 mins | Standard Deviation 12.78 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest | Baseline - Minutes patient could run without rest | 7.4 mins | Standard Deviation 10.02 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest | Change in Minutes patient could run without rest at Week 24 | -1.2 mins | Standard Deviation 13.56 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Run Without Rest | Change in Minutes patient could run without rest at Week 4 | -0.7 mins | Standard Deviation 8.64 |
Secondary
Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest
Minutes patient could walk without rest will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48.
Time frame: Baseline, Weeks 4, 24, and 48.
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest | Baseline - Minutes patient could walk without rest | 32 mins | Standard Deviation 28.25 |
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest | Change in Minutes patient could walk without rest at Week 4 | -2.1 mins | Standard Deviation 29.57 |
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest | Change in Minutes patient could walk without rest at Week 24 | -1.9 mins | Standard Deviation 26.3 |
| Investigational Product | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest | Change in Minutes patient could walk without rest at Week 48 | -5.8 mins | Standard Deviation 24.88 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest | Change in Minutes patient could walk without rest at Week 48 | 6.7 mins | Standard Deviation 28.95 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest | Baseline - Minutes patient could walk without rest | 28.6 mins | Standard Deviation 23.94 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest | Change in Minutes patient could walk without rest at Week 24 | -3.5 mins | Standard Deviation 12.63 |
| Placebo | Effect of L-glutamine on Subjective Exercise Tolerance - Minutes Patient Could Walk Without Rest | Change in Minutes patient could walk without rest at Week 4 | -1.8 mins | Standard Deviation 20.06 |
Secondary
Effect of L-glutamine on Tobacco Use
Patient's alcohol usage will be assessed at each visit. Alcohol usage will be reported at Weeks 0, 8,16, 24, 32, 40 and 48
Time frame: Weeks 0, 8,16, 24, 32, 40 and 48
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 8 | NO - Tobacco use | 23 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 24 | NO - Tobacco use | 20 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 40 | NO - Tobacco use | 17 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 24 | YES - Tobacco use | 2 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 8 | YES - Tobacco use | 3 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 32 | NO - Tobacco use | 18 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 0 | YES - Tobacco use | 5 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 16 | NO - Tobacco use | 24 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 40 | YES - Tobacco use | 1 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 0 | NO - Tobacco use | 28 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 48 | NO - Tobacco use | 16 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 16 | YES - Tobacco use | 4 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 48 | YES - Tobacco use | 1 Participants |
| Investigational Product | Effect of L-glutamine on Tobacco Use | Week 32 | YES - Tobacco use | 1 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 48 | YES - Tobacco use | 0 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 32 | YES - Tobacco use | 0 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 0 | NO - Tobacco use | 27 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 0 | YES - Tobacco use | 2 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 8 | NO - Tobacco use | 21 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 8 | YES - Tobacco use | 1 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 16 | NO - Tobacco use | 22 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 16 | YES - Tobacco use | 0 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 24 | NO - Tobacco use | 19 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 24 | YES - Tobacco use | 1 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 32 | NO - Tobacco use | 15 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 40 | NO - Tobacco use | 13 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 40 | YES - Tobacco use | 0 Participants |
| Placebo | Effect of L-glutamine on Tobacco Use | Week 48 | NO - Tobacco use | 12 Participants |
Secondary
Effect of Oral L--glutamine on Height
Height will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48
Time frame: Baseline, Weeks 4, 24, and 48
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | Effect of Oral L--glutamine on Height | Baseline | 169.8 cm | Standard Deviation 9.49 |
| Investigational Product | Effect of Oral L--glutamine on Height | Change in Height at Week 4 | -0.1 cm | Standard Deviation 1.18 |
| Investigational Product | Effect of Oral L--glutamine on Height | Change in Height at Week 24 | 0.1 cm | Standard Deviation 1.54 |
| Investigational Product | Effect of Oral L--glutamine on Height | Change in Height at Week 48 | -1.7 cm | Standard Deviation 6.58 |
| Placebo | Effect of Oral L--glutamine on Height | Change in Height at Week 48 | 0.4 cm | Standard Deviation 3.35 |
| Placebo | Effect of Oral L--glutamine on Height | Baseline | 169.2 cm | Standard Deviation 11.87 |
| Placebo | Effect of Oral L--glutamine on Height | Change in Height at Week 24 | -0.1 cm | Standard Deviation 1.68 |
| Placebo | Effect of Oral L--glutamine on Height | Change in Height at Week 4 | 0.2 cm | Standard Deviation 2.87 |
Secondary
Effect of Oral L--glutamine on Weight
Weight will be measured at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48
Time frame: Baseline, Weeks 4, 24 and 48
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | Effect of Oral L--glutamine on Weight | Baseline | 67.1 kg | Standard Deviation 13.39 |
| Investigational Product | Effect of Oral L--glutamine on Weight | Change in Weight at Week 4 | 0.8 kg | Standard Deviation 1.89 |
| Investigational Product | Effect of Oral L--glutamine on Weight | Change in Weight at Week 24 | 1.2 kg | Standard Deviation 2.55 |
| Investigational Product | Effect of Oral L--glutamine on Weight | Change in Weight at Week 48 | -1.0 kg | Standard Deviation 10.79 |
| Placebo | Effect of Oral L--glutamine on Weight | Change in Weight at Week 48 | 1.9 kg | Standard Deviation 7.39 |
| Placebo | Effect of Oral L--glutamine on Weight | Baseline | 70.7 kg | Standard Deviation 18.2 |
| Placebo | Effect of Oral L--glutamine on Weight | Change in Weight at Week 24 | 1.4 kg | Standard Deviation 5.04 |
| Placebo | Effect of Oral L--glutamine on Weight | Change in Weight at Week 4 | 0.1 kg | Standard Deviation 3.13 |
Secondary
Energy Level (11-point Scale)
The patient's energy level was evaluated at each visit using an 11 point scale from 0=extremely tired to 10=extremely energetic
Time frame: Collected at Week 0, 8, 16, 24, 32, 40, 48
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | Energy Level (11-point Scale) | Week 24 | 7.3 score on a scale | Standard Deviation 1.65 |
| Investigational Product | Energy Level (11-point Scale) | Week 32 | 7.3 score on a scale | Standard Deviation 1.67 |
| Investigational Product | Energy Level (11-point Scale) | Week 8 | 6.9 score on a scale | Standard Deviation 1.84 |
| Investigational Product | Energy Level (11-point Scale) | Week40 | 6.6 score on a scale | Standard Deviation 1.54 |
| Investigational Product | Energy Level (11-point Scale) | Week 0 | 6.1 score on a scale | Standard Deviation 1.92 |
| Investigational Product | Energy Level (11-point Scale) | Week 48 | 6.8 score on a scale | Standard Deviation 1.92 |
| Investigational Product | Energy Level (11-point Scale) | Week 16 | 6.9 score on a scale | Standard Deviation 2.02 |
| Placebo | Energy Level (11-point Scale) | Week 48 | 7.3 score on a scale | Standard Deviation 1.83 |
| Placebo | Energy Level (11-point Scale) | Week 16 | 7.1 score on a scale | Standard Deviation 2.7 |
| Placebo | Energy Level (11-point Scale) | Week 0 | 6.8 score on a scale | Standard Deviation 1.99 |
| Placebo | Energy Level (11-point Scale) | Week 8 | 7.1 score on a scale | Standard Deviation 1.96 |
| Placebo | Energy Level (11-point Scale) | Week 24 | 7.8 score on a scale | Standard Deviation 2.02 |
| Placebo | Energy Level (11-point Scale) | Week 32 | 7.4 score on a scale | Standard Deviation 1.95 |
| Placebo | Energy Level (11-point Scale) | Week40 | 6.9 score on a scale | Standard Deviation 2.29 |
Secondary
Frequency of Emergency Room Visits for Sickle Cell Pain
The mean number of emergency room visits through week 48
Time frame: From Week 0 through Week 48 (cumulative)
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Investigational Product | Frequency of Emergency Room Visits for Sickle Cell Pain | 3.7 Emergency room visits | Standard Deviation 5.63 |
| Placebo | Frequency of Emergency Room Visits for Sickle Cell Pain | 9.4 Emergency room visits | Standard Deviation 19.91 |
p-value: 0.129Cochran-Mantel-Haenszel
Secondary
Frequency of Hospitalizations for Sickle Cell Pain
The mean number of hospitalizations through week 48
Time frame: From Week 0 through Week 48 (cumulative)
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Investigational Product | Frequency of Hospitalizations for Sickle Cell Pain | 1.5 Hosptalizations | Standard Deviation 2.46 |
| Placebo | Frequency of Hospitalizations for Sickle Cell Pain | 2.3 Hosptalizations | Standard Deviation 2.42 |
p-value: 0.072Cochran-Mantel-Haenszel
Secondary
Number of Participants With Narcotic Usage
Analysis of narcotic usage was performed for the subset of patients with any narcotic use who completed the study. Changes in narcotic usage were determined by an independent consultant prior to database lock using morphine equivalents to determine relative use.
Time frame: Week 24, Week 48
Population: Patients with any narcotic use who completed the visit
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Investigational Product | Number of Participants With Narcotic Usage | Change in Narcotic Usage at Week 24 | Change to weaker narcotics | 6 Participants |
| Investigational Product | Number of Participants With Narcotic Usage | Change in Narcotic Usage at Week 24 | No change | 10 Participants |
| Investigational Product | Number of Participants With Narcotic Usage | Change in Narcotic Usage at Week 24 | Change to stronger narcotics | 1 Participants |
| Investigational Product | Number of Participants With Narcotic Usage | Change in Narcotic Usage at Week 48 | Change to weaker narcotics | 6 Participants |
| Investigational Product | Number of Participants With Narcotic Usage | Change in Narcotic Usage at Week 48 | No change | 10 Participants |
| Investigational Product | Number of Participants With Narcotic Usage | Change in Narcotic Usage at Week 48 | Change to stronger narcotics | 1 Participants |
| Placebo | Number of Participants With Narcotic Usage | Change in Narcotic Usage at Week 48 | No change | 9 Participants |
| Placebo | Number of Participants With Narcotic Usage | Change in Narcotic Usage at Week 24 | Change to weaker narcotics | 2 Participants |
| Placebo | Number of Participants With Narcotic Usage | Change in Narcotic Usage at Week 48 | Change to weaker narcotics | 2 Participants |
| Placebo | Number of Participants With Narcotic Usage | Change in Narcotic Usage at Week 24 | No change | 9 Participants |
| Placebo | Number of Participants With Narcotic Usage | Change in Narcotic Usage at Week 48 | Change to stronger narcotics | 5 Participants |
| Placebo | Number of Participants With Narcotic Usage | Change in Narcotic Usage at Week 24 | Change to stronger narcotics | 5 Participants |
Secondary
Patient Appetite (3-point Scale)
Patient's appetite level was evaluated at each visit using a 3 point scale: above average, average and below average. The parentages of patient at each visit whose appetite level was below, normal or above average were compared using CMH test (row mean scores) controlling for study center.
Time frame: Collected at Week 0, 8, 16, 24, 32, 40, 48
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 0 | Average | 24 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 24 | Average | 17 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 24 | Below average | 1 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 8 | Average | 19 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 24 | Not known | 0 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 16 | Average | 18 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 32 | Average | 15 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 8 | Below average | 2 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 32 | Below average | 1 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 0 | Below average | 5 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 32 | Not known | 0 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 8 | Not known | 1 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 40 | Above average | 2 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 0 | Above average | 4 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 40 | Average | 13 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 0 | Not known | 0 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 40 | Below average | 3 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 16 | Below average | 7 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 40 | Not known | 0 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 32 | Above average | 3 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 48 | Above average | 2 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 16 | Not known | 0 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 48 | Average | 13 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 8 | Above average | 4 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 48 | Below average | 2 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 24 | Above average | 4 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 48 | Not known | 0 Participants |
| Investigational Product | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 16 | Above average | 3 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 48 | Not known | 0 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 16 | Above average | 9 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 24 | Average | 11 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 32 | Above average | 3 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 0 | Above average | 6 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 0 | Average | 22 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 0 | Below average | 1 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 0 | Not known | 0 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 8 | Above average | 6 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 8 | Average | 14 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 8 | Below average | 2 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 8 | Not known | 0 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 16 | Average | 11 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 16 | Below average | 2 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 16 | Not known | 0 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 24 | Above average | 7 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 24 | Below average | 2 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 24 | Not known | 0 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 32 | Average | 12 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 32 | Below average | 0 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 32 | Not known | 0 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 40 | Above average | 4 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 40 | Average | 7 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 40 | Below average | 2 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 40 | Not known | 0 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 48 | Above average | 2 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 48 | Average | 9 Participants |
| Placebo | Patient Appetite (3-point Scale) | Patient appetite since the last visit - Visit 48 | Below average | 1 Participants |
Secondary
The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit
Patient's hematocrit will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24 and 40
Time frame: Baseline, Weeks 4, 24, and 40
Population: The safety population included all patients who received at least one dose of study medication (N = 70).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit | Baseline | 25.90 % RBC | Standard Deviation 4.493 |
| Investigational Product | The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit | Change in Hematocrit at Week 4 | 0.51 % RBC | Standard Deviation 2.784 |
| Investigational Product | The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit | Change in Hematocrit at Week 24 | 1.08 % RBC | Standard Deviation 2.352 |
| Investigational Product | The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit | Change in Hematocrit at Week 40 | 0.49 % RBC | Standard Deviation 2.786 |
| Placebo | The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit | Change in Hematocrit at Week 40 | 0.26 % RBC | Standard Deviation 1.869 |
| Placebo | The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit | Baseline | 26.22 % RBC | Standard Deviation 4.125 |
| Placebo | The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit | Change in Hematocrit at Week 24 | 0.58 % RBC | Standard Deviation 2.05 |
| Placebo | The Effect of Oral L-glutamine on Hematological Parameters - Hematocrit | Change in Hematocrit at Week 4 | -0.09 % RBC | Standard Deviation 2.279 |
Secondary
The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin
Patient's hemoglobin will be collected at each visit.Change from Baseline will be reported at Weeks 4, 24 and 40.
Time frame: Baseline, Weeks 4, 24 and 40
Population: The safety population included all patients who received at least one dose of study medication (N = 70).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin | Baseline | 8.96 g/dL | Standard Deviation 1.477 |
| Investigational Product | The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin | Change in Hemoglobin at Week 4 | 0.15 g/dL | Standard Deviation 0.831 |
| Investigational Product | The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin | Change in Hemoglobin at Week 24 | 0.26 g/dL | Standard Deviation 0.641 |
| Investigational Product | The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin | Change in Hemoglobin at Week 40 | 0.11 g/dL | Standard Deviation 0.749 |
| Placebo | The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin | Change in Hemoglobin at Week 40 | -0.07 g/dL | Standard Deviation 0.65 |
| Placebo | The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin | Baseline | 9.05 g/dL | Standard Deviation 1.219 |
| Placebo | The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin | Change in Hemoglobin at Week 24 | 0.16 g/dL | Standard Deviation 0.607 |
| Placebo | The Effect of Oral L-glutamine on Hematological Parameters - Hemoglobin | Change in Hemoglobin at Week 4 | -0.13 g/dL | Standard Deviation 0.861 |
Secondary
The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count
Patient's reticulocyte count will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24 and 40
Time frame: Baseline, Weeks 0, 4, 24, 40
Population: The safety population included all patients who received at least one dose of study medication (N = 70).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count | Baseline | 0.266 10^12 Reticulocytes/L | Standard Deviation 0.1125 |
| Investigational Product | The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count | Change in Reticulocyte count at Week 4 | -0.040 10^12 Reticulocytes/L | Standard Deviation 0.0993 |
| Investigational Product | The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count | Change in Reticulocyte count at Week 24 | -0.022 10^12 Reticulocytes/L | Standard Deviation 0.0917 |
| Investigational Product | The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count | Change in Reticulocyte count at Week 40 | -0.016 10^12 Reticulocytes/L | Standard Deviation 0.1357 |
| Placebo | The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count | Change in Reticulocyte count at Week 40 | -0.020 10^12 Reticulocytes/L | Standard Deviation 0.0908 |
| Placebo | The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count | Baseline | 0.295 10^12 Reticulocytes/L | Standard Deviation 0.0979 |
| Placebo | The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count | Change in Reticulocyte count at Week 24 | -0.032 10^12 Reticulocytes/L | Standard Deviation 0.1032 |
| Placebo | The Effect of Oral L-glutamine on Hematological Parameters - Reticulocyte Count | Change in Reticulocyte count at Week 4 | -0.034 10^12 Reticulocytes/L | Standard Deviation 0.0689 |
Secondary
The Effect of Oral L-glutamine on Subjective Quality of Life
The subjective quality of life was evaluated using the scoring of the RAND 36-Item Health Survey Questionnaire. The subjective quality of life (Physical functioning, Physical health, Emotional problems, Energy/Fatigue, Emotional well being, Social functioning, Pain, General health) will be reported at Baseline and Week 24 (or at time of discontinuation). The range for Physical functioning, Physical health, Emotional problems, Emotional well being and Social functioning is 0-100, with a high score denotes a better quality of life. For Energy/Fatigue, Pain and General health the range is 0-100, with a lower score denotes better quality of life.
Time frame: Baseline and Week 24 (or at time of discontinuation)
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Emotional Well Being - Week 24 | 71.9 score on a scale | Standard Deviation 17.83 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Emotional Well Being - Baseline | 66.2 score on a scale | Standard Deviation 19.37 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Physical Health - Week 24 | 55.6 score on a scale | Standard Deviation 41.79 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Physical Functioning Baseline | 61.7 score on a scale | Standard Deviation 25.38 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Social Functioning - Baseline | 61.3 score on a scale | Standard Deviation 24.01 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Emotional Problems - Baseline | 52.7 score on a scale | Standard Deviation 41.97 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Social Functioning - Week 24 | 72.5 score on a scale | Standard Deviation 22.06 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Energy/Fatigue - Baseline | 45.7 score on a scale | Standard Deviation 12.29 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Pain - Baseline | 53.4 score on a scale | Standard Deviation 23.41 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Emotional Problems - Week 24 | 58.3 score on a scale | Standard Deviation 40.2 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Pain - Week 24 | 59.1 score on a scale | Standard Deviation 24.6 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Physical Functioning Week 24 | 65.5 score on a scale | Standard Deviation 23.18 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | General Health - Baseline | 46.0 score on a scale | Standard Deviation 17.42 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Physical Health - Baseline | 43.5 score on a scale | Standard Deviation 38.17 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | General Health - Week 24 | 53.9 score on a scale | Standard Deviation 16.55 |
| Investigational Product | The Effect of Oral L-glutamine on Subjective Quality of Life | Energy/Fatigue - Week 24 | 49.8 score on a scale | Standard Deviation 19.65 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | General Health - Week 24 | 57.0 score on a scale | Standard Deviation 18.62 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Physical Functioning Baseline | 69.9 score on a scale | Standard Deviation 26.68 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Physical Health - Baseline | 49.1 score on a scale | Standard Deviation 40.72 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Physical Health - Week 24 | 46.7 score on a scale | Standard Deviation 40.83 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Emotional Problems - Baseline | 66.7 score on a scale | Standard Deviation 41.35 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Emotional Problems - Week 24 | 65.3 score on a scale | Standard Deviation 40.24 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Energy/Fatigue - Baseline | 50.0 score on a scale | Standard Deviation 17.82 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Energy/Fatigue - Week 24 | 53.4 score on a scale | Standard Deviation 21.96 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Emotional Well Being - Baseline | 74.5 score on a scale | Standard Deviation 16.02 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Emotional Well Being - Week 24 | 77.1 score on a scale | Standard Deviation 21.92 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Social Functioning - Baseline | 62.5 score on a scale | Standard Deviation 24.27 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Social Functioning - Week 24 | 65.6 score on a scale | Standard Deviation 26.02 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Pain - Baseline | 55.5 score on a scale | Standard Deviation 28.07 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Pain - Week 24 | 56.1 score on a scale | Standard Deviation 30.76 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | General Health - Baseline | 49.7 score on a scale | Standard Deviation 21.5 |
| Placebo | The Effect of Oral L-glutamine on Subjective Quality of Life | Physical Functioning Week 24 | 76.0 score on a scale | Standard Deviation 17.38 |
Secondary
The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain
Percentage of days a patient's daily activities were interrupted due to sickle pain calculated at each visit. Day's interrupted will be reported at Weeks 0, 8,16, 24, 32, 40 and 48
Time frame: Weeks 0, 8,16, 24, 32, 40 and 48
Population: The full analysis dataset included all patients who received at least one dose of study medication and had been diagnosed with sickle cell anemia or sickle β°-thalassemia documented by hemoglobin electrophoresis and had at least 2 episodes of painful crises within 12 months prior to the screening visit (N = 62)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 40 | 13.2 % of days interrupted | Standard Deviation 16.88 |
| Investigational Product | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 48 | 11.7 % of days interrupted | Standard Deviation 19.17 |
| Investigational Product | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 0 | 8.3 % of days interrupted | Standard Deviation 11.19 |
| Investigational Product | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 8 | 11.9 % of days interrupted | Standard Deviation 21.22 |
| Investigational Product | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 24 | 11.4 % of days interrupted | Standard Deviation 18.34 |
| Investigational Product | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 32 | 12.5 % of days interrupted | Standard Deviation 17.96 |
| Investigational Product | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 16 | 23.3 % of days interrupted | Standard Deviation 28.56 |
| Placebo | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 24 | 11.7 % of days interrupted | Standard Deviation 12.75 |
| Placebo | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 16 | 15.5 % of days interrupted | Standard Deviation 21.55 |
| Placebo | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 40 | 28.0 % of days interrupted | Standard Deviation 31.33 |
| Placebo | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 8 | 24.2 % of days interrupted | Standard Deviation 29.22 |
| Placebo | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 48 | 11.5 % of days interrupted | Standard Deviation 17.58 |
| Placebo | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 32 | 15.7 % of days interrupted | Standard Deviation 17.33 |
| Placebo | The Effect of Oral L-glutamine on the Number of Days Patient's Daily Activities Are Interrupted Due to Sickle Cell Pain | Week 0 | 8.1 % of days interrupted | Standard Deviation 11.94 |
Secondary
The Effect of Oral L-glutamine on Vital Signs - Blood Pressure
Patient's blood pressure will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48
Time frame: Baseline, Weeks 4, 24, and 48
Population: The safety population included all patients who received at least one dose of study medication (N = 70).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Baseline SBP (mm/Hg) | 115.18 mm/Hg | Standard Deviation 14.3 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Change in SBP (mm/Hg) at Week 4 | 0.7 mm/Hg | Standard Deviation 10.98 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Change in SBP (mm/Hg) at Week 24 | 2.2 mm/Hg | Standard Deviation 10.48 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Change in SBP (mm/Hg) at Week 48 | -1.2 mm/Hg | Standard Deviation 12.07 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Baseline DBP (mm/hg) | 63.7 mm/Hg | Standard Deviation 9.05 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Change in DBP (mm/Hg) at Week 4 | 1.2 mm/Hg | Standard Deviation 8.09 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Change in DBP (mm/Hg) at Week 24 | 1.2 mm/Hg | Standard Deviation 9.55 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Change in DBP (mm/Hg) at Week 48 | -1.3 mm/Hg | Standard Deviation 7.98 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Change in DBP (mm/Hg) at Week 48 | 0.5 mm/Hg | Standard Deviation 7.91 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Baseline SBP (mm/Hg) | 119.6 mm/Hg | Standard Deviation 13.64 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Baseline DBP (mm/hg) | 64.9 mm/Hg | Standard Deviation 8.09 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Change in SBP (mm/Hg) at Week 4 | -0.9 mm/Hg | Standard Deviation 10.81 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Change in DBP (mm/Hg) at Week 24 | -0.4 mm/Hg | Standard Deviation 6.88 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Change in SBP (mm/Hg) at Week 24 | -1.9 mm/Hg | Standard Deviation 13.06 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Change in DBP (mm/Hg) at Week 4 | 2.2 mm/Hg | Standard Deviation 8.73 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Blood Pressure | Change in SBP (mm/Hg) at Week 48 | -1.5 mm/Hg | Standard Deviation 12.97 |
Secondary
The Effect of Oral L-glutamine on Vital Signs - Pulse Rate
Patient's pulse rate will be collected at each visit, Change from Baseline will be reported at Weeks 4, 24, and 48
Time frame: Baseline, Weeks 4, 24, and 48
Population: The safety population included all patients who received at least one dose of study medication (N = 70).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Pulse Rate | Baseline | 81.6 bpm | Standard Deviation 11.37 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Pulse Rate | Change in Pulse Rate at Week 4 | 2.5 bpm | Standard Deviation 12.88 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Pulse Rate | Change in Pulse Rate at Week 24 | 1.7 bpm | Standard Deviation 13.69 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Pulse Rate | Change in Pulse Rate at Week 48 | 1.3 bpm | Standard Deviation 14.53 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Pulse Rate | Change in Pulse Rate at Week 48 | 3.9 bpm | Standard Deviation 10.07 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Pulse Rate | Baseline | 80.5 bpm | Standard Deviation 11.95 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Pulse Rate | Change in Pulse Rate at Week 24 | -2.7 bpm | Standard Deviation 12.81 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Pulse Rate | Change in Pulse Rate at Week 4 | 0.7 bpm | Standard Deviation 12.11 |
Secondary
The Effect of Oral L-glutamine on Vital Signs - Respiration
Respiration will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48
Time frame: Baseline, Weeks 4, 24, and 48
Population: The safety population included all patients who received at least one dose of study medication (N = 70).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Respiration | Baseline | 17.9 resp/min | Standard Deviation 2.11 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Respiration | Change in Respiration at Week 4 | 0.3 resp/min | Standard Deviation 1.71 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Respiration | Change in Respiration at Week 24 | 0.4 resp/min | Standard Deviation 1.73 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Respiration | Change in Respiration at Week 48 | 0.4 resp/min | Standard Deviation 2.12 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Respiration | Change in Respiration at Week 48 | 0.6 resp/min | Standard Deviation 2.47 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Respiration | Baseline | 17.7 resp/min | Standard Deviation 1.94 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Respiration | Change in Respiration at Week 24 | -0.4 resp/min | Standard Deviation 1.93 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Respiration | Change in Respiration at Week 4 | 0.6 resp/min | Standard Deviation 1.58 |
Secondary
The Effect of Oral L-glutamine on Vital Signs - Temperature
Patient's temperature will be collected at each visit. Change from Baseline will be reported at Weeks 4, 24, and 48
Time frame: Baseline, Weeks 4, 24, and 48
Population: The safety population included all patients who received at least one dose of study medication (N = 70).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Temperature | Baseline | 36.40 deg C | Standard Deviation 0.686 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Temperature | Change in Temperature at Week 4 | -0.05 deg C | Standard Deviation 0.377 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Temperature | Change Temperature at Week 24 | -0.01 deg C | Standard Deviation 0.261 |
| Investigational Product | The Effect of Oral L-glutamine on Vital Signs - Temperature | Change in Temperature at Week 48 | 0.08 deg C | Standard Deviation 0.362 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Temperature | Change in Temperature at Week 48 | -0.09 deg C | Standard Deviation 0.256 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Temperature | Baseline | 36.29 deg C | Standard Deviation 0.613 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Temperature | Change Temperature at Week 24 | -0.07 deg C | Standard Deviation 0.268 |
| Placebo | The Effect of Oral L-glutamine on Vital Signs - Temperature | Change in Temperature at Week 4 | -0.06 deg C | Standard Deviation 0.269 |