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

Gastroparesis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01135186
• Other study ID #: SU-03252010-5462
• Status: Completed
• Phase: N/A
• Start date: May 2010
• Est. completion date: November 2012

Study information

• Verified date: September 2019
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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)

Exclusion Criteria:Exclusion Criteria

Patients who satisfy any of the following exclusion criteria will be ineligible for enrollment in the study:

1. Diabetes diagnosed < 5 years prior to the study

2. Male gender

3. Normal gastric emptying

4. Gastroparesis from post-surgical etiologies

5. Another active disorder, which could explain symptoms in the opinion of the investigator

6. Pregnancy

7. History of significant cardiac arrhythmias and/or prolonged QTc

8. Daily use of narcotic analgesics for abdominal pain

9. Contraindications to gastric emptying breath test: patients with a known allergy to egg, wheat, or algae.

10. Underlying seizure disorder

11. Known history of cardiac ischemia

12. Recent clinically significant gastrointestinal bleeding

13. Patients taking Levodopa

14. Any other condition, which in the opinion of the investigator would impede compliance or hinder the completion of the study

15. Failure to give informed consent

16. 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).

17. A normal upper endoscopy not performed within 2 year of study entry.

18. Patients taking phosphodiesterase inhibitors such as sildenafil, vardenafil, tadalafil

19. Patients with renal impairment (i.e. Creatinine > 2.5 mg/dL)

20. Patients with hepatic dysfunction (i.e. ALT and AST values > 2.5x ULN and T. bilirubin > 1.5x ULN)

21. Patients with uncontrolled diabetes, such as HbA1c > 10 mg/dl at screening/baseline will be excluded.

Related Conditions & MeSH terms

• Gastroparesis

Intervention

Drug:
• sapropterin dihydrochloride
sapropterin dihydrochloride: 10mg/kg/day

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (6)

Bell RA, Jones-Vessey K, Summerson JH. Hospitalizations and outcomes for diabetic gastroparesis in North Carolina. South Med J. 2002 Nov;95(11):1297-9. — View Citation

Gangula PR, Maner WL, Micci MA, Garfield RE, Pasricha PJ. Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum. Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G725-33. — View Citation

Smirnova VI, Gridchik IE, Tregubenko AD, Khachaturova EA. [Analgesia and intensive therapy during hemicorporectomy]. Anesteziol Reanimatol. 1991 Sep-Oct;(5):46-8. Russian. — View Citation

Soykan I, Sivri B, Sarosiek I, Kiernan B, McCallum RW. Demography, clinical characteristics, psychological and abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. Dig Dis Sci. 1998 Nov;43(11):2398-404. — View Citation

Stacher G. Diabetes mellitus and the stomach. Diabetologia. 2001 Sep;44(9):1080-93. Review. Erratum in: Diabetologia 2002 Feb;45(2):293. — View Citation

Werner ER, Gorren AC, Heller R, Werner-Felmayer G, Mayer B. Tetrahydrobiopterin and nitric oxide: mechanistic and pharmacological aspects. Exp Biol Med (Maywood). 2003 Dec;228(11):1291-302. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline, 4 Weeks, 8 Weeks
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.	Baseline, 4 Weeks, 8 Weeks
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.	Baseline, 4 Weeks, 8 Weeks
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.	Baseline, 4 Weeks, 8 Weeks