Clinical trial NCT01135186: Impact of KUVAN® on Gastric Relaxation in Women With Diabetic Gastroparesis.
Official title: Kuvan® (Sapropterin Dihydrochloride) for Improving Gastric Accommodation in Women With Diabetic Gastroparesis (KIGA-DG)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastroparesis
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2010-06-02
Enrollment: 9
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Gastric Accommodation
timeFrame: Baseline, 4 Weeks, 8 Weeks
Secondary outcomes:
measure: Secondary Outcome Measures Will Include Change in Symptom Severity.
timeFrame: Baseline, 4 Weeks, 8 Weeks
measure: Secondary Outcome Measures Will Include Change in Quality of Life.
timeFrame: Baseline, 4 Weeks, 8 Weeks
measure: 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)
timeFrame: Baseline, 4 Weeks, 8 Weeks
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Linda A Nguyen
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Pankaj Jay Pasricha
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: Stacher G. Diabetes mellitus and the stomach. Diabetologia. 2001 Sep;44(9):1080-93. doi: 10.1007/s001250100619.
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. doi: 10.1152/ajpgi.00406.2006.
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. doi: 10.1177/153537020322801108.
citation: Smirnova VI, Gridchik IE, Tregubenko AD, Khachaturova EA. [Analgesia and intensive therapy during hemicorporectomy]. Anesteziol Reanimatol. 1991 Sep-Oct;(5):46-8. Russian.