Impact of KUVAN® on Gastric Relaxation in Women With Diabetic Gastroparesis.

Study Overview
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Brief Summary
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Kuvan® (sapropterin dihydrochloride) for Improving Gastric Accommodation in Women with Diabetic Gastroparesis (KIGA-DG)

Detailed Description
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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).

Official Title
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Kuvan® (Sapropterin Dihydrochloride) for Improving Gastric Accommodation in Women With Diabetic Gastroparesis (KIGA-DG)

Conditions
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Gastroparesis

Intervention / Treatment
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* Drug: sapropterin dihydrochloride


Participation Criteria
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Eligibility Criteria
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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: Diagnosis of diabetes mellitus > 5 years requiring medical therapy Female gender Ages 18-65 years Documentation of delayed gastric emptying on gastric emptying scintigraphy (within 2 years of enrollment) Symptoms of gastroparesis for at least 6 months with Gastroparesis Cardinal Symptom Index (GCSI) score > 21 indicating moderate to severe symptoms Recent negative upper endoscopy or upper GI series within 2 years of enrollment (no evidence of mechanical obstruction or peptic ulcer disease) Exclusion Criteria:Exclusion Criteria Patients who satisfy any of the following exclusion criteria will be ineligible for enrollment in the study: Diabetes diagnosed < 5 years prior to the study Male gender Normal gastric emptying Gastroparesis from post-surgical etiologies Another active disorder, which could explain symptoms in the opinion of the investigator Pregnancy History of significant cardiac arrhythmias and/or prolonged QTc Daily use of narcotic analgesics for abdominal pain Contraindications to gastric emptying breath test: patients with a known allergy to egg, wheat, or algae. Underlying seizure disorder Known history of cardiac ischemia Recent clinically significant gastrointestinal bleeding Patients taking Levodopa Any other condition, which in the opinion of the investigator would impede compliance or hinder the completion of the study Failure to give informed consent Surgery for placement of a gastric stimulator within the past 6 months (patients > 6 months post-op with persistent symptoms and delayed gastric emptying are eligible). A normal upper endoscopy not performed within 2 year of study entry. Patients taking phosphodiesterase inhibitors such as sildenafil, vardenafil, tadalafil Patients with renal impairment (i.e. Creatinine > 2.5 mg/dL) Patients with hepatic dysfunction (i.e. ALT and AST values > 2.5x ULN and T. bilirubin > 1.5x ULN) Patients with uncontrolled diabetes, such as HbA1c > 10 mg/dl at screening/baseline will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sapropterin<br>open label study of sapropterin dihydrochloride | Drug: sapropterin dihydrochloride<br>* sapropterin dihydrochloride: 10mg/kg/day<br>* Other names: KUVAN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, 4 Weeks, 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, 4 Weeks, 8 Weeks | 
| 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. | Baseline, 4 Weeks, 8 Weeks | 
| 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. | Baseline, 4 Weeks, 8 Weeks |