Sickle Cell Disease
Conditions
Keywords
sickle cell disease, sickle cell anemia, pain crisis, nitric oxide, nitrite, vaso occlusive crisis, pain medication, sickled cells, blood flow, microcirculation
Brief summary
This study will determine if administration of sodium nitrite is safe and can improve small vessel blood flow and tissue oxygenation when given as an additional treatment in patients with acute vaso-occlusive crisis (pain crisis) associated with sickle cell disease.
Detailed description
Nitric oxide (NO) is a naturally occuring chemical that relaxes blood vessels and helps improve blood flow. The pain associated with vaso-occlusive crisis (pain crisis) in sickle cell disease is caused in part by lack of oxygen and increased tissue acid because blood flow is blocked by stiff sickle red cells. Administration of sodium nitrite should generate nitric oxide in this area of hypoxia and acidosis and improve blood flow.
Interventions
DRUGsodium nitrite injection, usp
Sodium nitrite injection, USP will be administered in blocks of six subjects (3 sodium nitrite and 3 no drug). A total of five dose levels are planned, pending safety starting. Drug will be given by continuous infusion infusion for 48 hours starting at 6 nmol/min/kg (10% of the maximal tolerated dose).
Sponsors
Hope Pharmaceuticals
Children's Hospital Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 23 Years
Healthy volunteers
No
Inclusion criteria
Subjects meeting all of the following criteria will be considered for admission to the study: 1. Male or female subject aged between 8 and 23 years of age; only patients up to the age of 23 will be studied at Childrens Hospital Los Angeles 2. Electrophoretic diagnosis of sickle cell disease; 3. Sudden onset of acute pain involving \>=1 sites typical of vaso-occlusive crisis (Vaso-occlusive crisis is defined as acute, severe pain in the extremities, chest, abdomen, or back that can not be explained by other complications of sickle cell disease or by a cause other than sickle cell disease.); 4. Severe pain requiring parenteral analgesics and hospitalization. 5. Informed consent obtained from a legal representative or from subjects 18 years of age or older before enrollment; 6. Being willing and able to be followed for at least 30 days for evaluation.
Exclusion criteria
Subjects presenting with any of the following will not be included in the study: 1. Clinically significant bleeding; 2. Current drug abuse or participation in methadone program; 3. Episode of pain requiring hospitalization within 2 weeks prior to current admission; 4. Other complications of sickle cell disease including cerebrovascular accident, pulmonary hypertension, or seizure; 5. Pregnancy (confirmed by a serum human chorionic gonadotropin pregnancy test) or breast feeding; 6. Blood pressure less than 25th percentile for the subject's age and sex on admission or at the time of screening; 7. Methemoglobinemia \>3%; 8. Anemia with hemoglobin level less than 6 g/dL; 9. Red blood cell G6PD deficiency, by laboratory testing prior to enrollment; 10. History of allergy to nitrites or allergy to other substances characterized by dyspnea and cyanosis; 11. Treatment with allopurinol, a medication that could interfere with nitrite metabolism, within the past 30 days before screening; 12. Treatment with any investigational drug within the past 30 days; 13. Significant acute or chronic concomitant diseases (including renal, hepatic, cardiovascular, pulmonary, or oncologic disease, sepsis, pulmonary edema, pulmonary embolism) that would be inconsistent with survival for at least 6 months; 14. Any subject judged by the clinical investigator or study manager to be inappropriate for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 48 Hour Sodium Nitrite Infusion Safety as Determined by Number of Participants With No Adverse Events | 48 hours from start of infusion | The primary end points will be to determine if a) a 48-hour sodium nitrite infusion is tolerated without a decrease in mean arterial blood pressure by 15mmHg for greater than 2 hours or development of methemoglobin greater than 5% and b) a 48-hour sodium nitrite infusion is safe as determined by monitoring for adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary End Point | 48 hours | a) reduced the duration and intensity of pain; b) reduced total narcotic analgesic consumption; and c) reduced length of hospitalization. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited for the study during regular clinic visits.
Pre-assignment details
Once consent signed subjects would not be randomized into the treatment arm until (if or when) they had their admission to the hospital for vaso-occlusive crisis (VOC).
Participants by arm
| Arm | Count |
|---|---|
| No Drug | 3 |
| Sodium Nitrite Injection, USP Administration if sodium nitrite injection, USP
sodium nitrite injection, usp: Sodium nitrite injection, USP will be administered in blocks of six subjects (3 sodium nitrite and 3 no drug). A total of five dose levels are planned, pending safety starting. Drug will be given by continuous infusion infusion for 48 hours starting at 6 nmol/min/kg (10% of the maximal tolerated dose). | 2 |
| Total | 5 |
Baseline characteristics
| Characteristic | No Drug | Sodium Nitrite Injection, USP | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Continuous | 16 years | 15.5 years | 16 years |
| Region of Enrollment United States | 3 participants | 2 participants | 5 participants |
| Sbeta+thalassemia | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Sickle Cell Disease hb SS | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 3 | 0 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
48 Hour Sodium Nitrite Infusion Safety as Determined by Number of Participants With No Adverse Events
The primary end points will be to determine if a) a 48-hour sodium nitrite infusion is tolerated without a decrease in mean arterial blood pressure by 15mmHg for greater than 2 hours or development of methemoglobin greater than 5% and b) a 48-hour sodium nitrite infusion is safe as determined by monitoring for adverse events
Time frame: 48 hours from start of infusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Drug | 48 Hour Sodium Nitrite Infusion Safety as Determined by Number of Participants With No Adverse Events | 3 Participants |
| Sodium Nitrite Injection, USP | 48 Hour Sodium Nitrite Infusion Safety as Determined by Number of Participants With No Adverse Events | 2 Participants |
Secondary
Secondary End Point
a) reduced the duration and intensity of pain; b) reduced total narcotic analgesic consumption; and c) reduced length of hospitalization.
Time frame: 48 hours
Population: Data were \*not collected\* and the Outcome was never analyzed, study terminated