Gastroparesis
Conditions
Brief summary
Kuvan® (sapropterin dihydrochloride) for Improving Gastric Accommodation in Women with Diabetic Gastroparesis (KIGA-DG)
Detailed description
Patients are invited to participate in a research study of Kuvan® (sapropterin dihydrochloride). We hope to learn whether treatment with Kuvan® is safe and effective in improving the ability of the stomach to relax after eating and improving the symptoms of diabetic gastroparesis. Women are selected as a possible participant in this study because they have diabetes and moderate to severe gastroparesis (meaning stomach empties slowly).
Interventions
sapropterin dihydrochloride: 10mg/kg/day
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria Patients with moderate to severe symptoms of diabetic gastroparesis will be studied (GCSI \>21). Patients should not have post-surgical gastroparesis or dyspeptic symptoms with normal gastric emptying. In order to qualify for inclusion in the trial, patients must satisfy the following inclusion criteria: 1. Diagnosis of diabetes mellitus \> 5 years requiring medical therapy 2. Female gender 3. Ages 18-65 years 4. Documentation of delayed gastric emptying on gastric emptying scintigraphy (within 2 years of enrollment) 5. Symptoms of gastroparesis for at least 6 months with Gastroparesis Cardinal Symptom Index (GCSI) score \> 21 indicating moderate to severe symptoms 6. Recent negative upper endoscopy or upper GI series within 2 years of enrollment (no evidence of mechanical obstruction or peptic ulcer disease)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastric Accommodation | Baseline, 4 Weeks, 8 Weeks | Gastric Accommodation refers to the reflexive relaxation of the upper stomach after swallowing as measured by the Satiety Test at baseline, 4 weeks, and 8 weeks. Increased gastric accommodation is considered a positive outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome Measures Will Include Change in Symptom Severity. | Baseline, 4 Weeks, 8 Weeks | Change in symptom severity over the past 2 weeks as measured by the patient reported Gastroparesis Cardinal Symptom Index (GCSI) The GCSI is composed of 9 questions. Each question asks about symptom severity on a scale of 1-5 listed below. 0=None 1= Very mild 2= Mild 3=Moderate 4=Severe 5= Very severe The 9 scores are summed together for cumulative GCSI score. The minimum cumulative score is '0 and the maximum cumulative score is 45. Once we calculated the cumulative score for each participant, we took the average of all participants cumulative scores giving us the sample mean. This was done at baseline, week 4, and week 8. Higher total scores indicate higher symptom severity. Lower total scores indicate lower symptom severity. |
| Secondary Outcome Measures Will Include Change in Quality of Life. | Baseline, 4 Weeks, 8 Weeks | Quality of life as impacted by patients with upper gastrointestinal disorders (PAGI-QOL) The PAGI-QOl is composed of 30 questions. Each question asks about the degree to which a patient's quality of life is impacted by upper gastrointestinal disorders. Questions measure quality of life impact on a scale of 1-5 listed below. 0=none of the time, 1=a little of the time, 2=some of the time, 3=a good bit of the time, 4= most of the time, 5= all of time The 30 items are summed together for a cumulative PAGI-QOL score. The minimum cumulative score is 0 and the maximum score is 150. Once we calculated the cumulative score for each participant, we took the average of all participants cumulative scores giving us the sample mean. This was done at baseline, week 4, and week 8. Lower scores indicate an improved overall quality of life. Higher scores indicate a diminished overall quality of life. |
| Secondary Outcome Measures Will Include Change in Symptom Severity as Measured by the Patient Assessment of Gastrointestinal Disorder-Symptom Severity Index Disorders Symptom Severity Index (PAGI-SYM) | Baseline, 4 Weeks, 8 Weeks | Symptom severity as measured by the Patient Assessment of Upper Gastrointestinal Disorder- Symptom Severity Index. (PAGI-SYM) The PAGI-SYM is compose of 20 questions. Each question can be answered on a scale of 1-5 (below) 0 = none, 1=very mild, 2=mild, 3=moderate, 4=severe, 5=very severe Cumulative scores were calculated by summing all 20 questions. The minimum cumulative scores would be 0 while the maximum cumulative score would be 100 Once we calculated the cumulative score for each participant, we took the average of all the cumulative scores giving us the sample mean. This was done at baseline, week 4, and week 8. Lower score indicates decreased symptom severity. Higher score indicates increased symptom severity. |
Countries
United States
Participant flow
Recruitment details
9 women with moderate to severe gastroparesis were enrolled at medical clinic.
Participants by arm
| Arm | Count |
|---|---|
| Open Label Study sapropterin dihydrochloride
sapropterin dihydrochloride: sapropterin dihydrochloride: 10mg/kg/day (week 1 through week 4)
sapropterin dihydrochloride: sapropterin dihydrochloride: 20mg/kg/day (week 5 through week 8) | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Open Label Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 42.56 years STANDARD_DEVIATION 15.03 |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 9 |
| serious Total, serious adverse events | 1 / 9 |
Outcome results
Primary
Gastric Accommodation
Gastric Accommodation refers to the reflexive relaxation of the upper stomach after swallowing as measured by the Satiety Test at baseline, 4 weeks, and 8 weeks. Increased gastric accommodation is considered a positive outcome.
Time frame: Baseline, 4 Weeks, 8 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label Study | Gastric Accommodation | Baseline | 322.22 ml | Standard Deviation 137.18 |
| Open Label Study | Gastric Accommodation | 4 Weeks | 402.78 ml | Standard Deviation 197.03 |
| Open Label Study | Gastric Accommodation | 8 Weeks | 450.63 ml | Standard Deviation 301.5 |
Secondary
Secondary Outcome Measures Will Include Change in Quality of Life.
Quality of life as impacted by patients with upper gastrointestinal disorders (PAGI-QOL) The PAGI-QOl is composed of 30 questions. Each question asks about the degree to which a patient's quality of life is impacted by upper gastrointestinal disorders. Questions measure quality of life impact on a scale of 1-5 listed below. 0=none of the time, 1=a little of the time, 2=some of the time, 3=a good bit of the time, 4= most of the time, 5= all of time The 30 items are summed together for a cumulative PAGI-QOL score. The minimum cumulative score is 0 and the maximum score is 150. Once we calculated the cumulative score for each participant, we took the average of all participants cumulative scores giving us the sample mean. This was done at baseline, week 4, and week 8. Lower scores indicate an improved overall quality of life. Higher scores indicate a diminished overall quality of life.
Time frame: Baseline, 4 Weeks, 8 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label Study | Secondary Outcome Measures Will Include Change in Quality of Life. | Baseline | 91.22 units on a scale | Standard Deviation 28.27 |
| Open Label Study | Secondary Outcome Measures Will Include Change in Quality of Life. | 4 Weeks | 61.29 units on a scale | Standard Deviation 37.83 |
| Open Label Study | Secondary Outcome Measures Will Include Change in Quality of Life. | 8 Weeks | 60.50 units on a scale | Standard Deviation 40.9 |
Secondary
Secondary Outcome Measures Will Include Change in Symptom Severity.
Change in symptom severity over the past 2 weeks as measured by the patient reported Gastroparesis Cardinal Symptom Index (GCSI) The GCSI is composed of 9 questions. Each question asks about symptom severity on a scale of 1-5 listed below. 0=None 1= Very mild 2= Mild 3=Moderate 4=Severe 5= Very severe The 9 scores are summed together for cumulative GCSI score. The minimum cumulative score is '0 and the maximum cumulative score is 45. Once we calculated the cumulative score for each participant, we took the average of all participants cumulative scores giving us the sample mean. This was done at baseline, week 4, and week 8. Higher total scores indicate higher symptom severity. Lower total scores indicate lower symptom severity.
Time frame: Baseline, 4 Weeks, 8 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label Study | Secondary Outcome Measures Will Include Change in Symptom Severity. | Baseline | 32.00 units on a scale | Standard Deviation 8.67 |
| Open Label Study | Secondary Outcome Measures Will Include Change in Symptom Severity. | 4 Weeks | 23.25 units on a scale | Standard Deviation 13.91 |
| Open Label Study | Secondary Outcome Measures Will Include Change in Symptom Severity. | 8 Weeks | 23.67 units on a scale | Standard Deviation 13.91 |
Secondary
Secondary Outcome Measures Will Include Change in Symptom Severity as Measured by the Patient Assessment of Gastrointestinal Disorder-Symptom Severity Index Disorders Symptom Severity Index (PAGI-SYM)
Symptom severity as measured by the Patient Assessment of Upper Gastrointestinal Disorder- Symptom Severity Index. (PAGI-SYM) The PAGI-SYM is compose of 20 questions. Each question can be answered on a scale of 1-5 (below) 0 = none, 1=very mild, 2=mild, 3=moderate, 4=severe, 5=very severe Cumulative scores were calculated by summing all 20 questions. The minimum cumulative scores would be 0 while the maximum cumulative score would be 100 Once we calculated the cumulative score for each participant, we took the average of all the cumulative scores giving us the sample mean. This was done at baseline, week 4, and week 8. Lower score indicates decreased symptom severity. Higher score indicates increased symptom severity.
Time frame: Baseline, 4 Weeks, 8 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label Study | Secondary Outcome Measures Will Include Change in Symptom Severity as Measured by the Patient Assessment of Gastrointestinal Disorder-Symptom Severity Index Disorders Symptom Severity Index (PAGI-SYM) | Baseline | 54.89 units on a scale | Standard Deviation 17.14 |
| Open Label Study | Secondary Outcome Measures Will Include Change in Symptom Severity as Measured by the Patient Assessment of Gastrointestinal Disorder-Symptom Severity Index Disorders Symptom Severity Index (PAGI-SYM) | 4 Weeks | 41.50 units on a scale | Standard Deviation 23.08 |
| Open Label Study | Secondary Outcome Measures Will Include Change in Symptom Severity as Measured by the Patient Assessment of Gastrointestinal Disorder-Symptom Severity Index Disorders Symptom Severity Index (PAGI-SYM) | 8 Weeks | 34.50 units on a scale | Standard Deviation 19.71 |