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

Back to results

Primary Purpose

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

sapropterin dihydrochloride

About this trial

This is an interventional treatment trial for Gastroparesis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Stanford University School of Medicine

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Sapropterin

Arm Description

open label study of sapropterin dihydrochloride

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT01135186

First Posted

May 28, 2010

Last Updated

September 6, 2019

Sponsor

Stanford University

1. Study Identification

Unique Protocol Identification Number

NCT01135186

Brief Title

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

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

May 2010 (undefined)

Primary Completion Date

November 2012 (Actual)

Study Completion Date

November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Stanford University

4. Oversight

Data Monitoring Committee

No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastroparesis

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sapropterin

Arm Type

Other

Arm Description

open label study of sapropterin dihydrochloride

Intervention Type

Drug

Intervention Name(s)

sapropterin dihydrochloride

Other Intervention Name(s)

KUVAN

Intervention Description

sapropterin dihydrochloride: 10mg/kg/day

Primary Outcome Measure Information:

Title

Gastric Accommodation

Description

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

Secondary Outcome Measure Information:

Title

Secondary Outcome Measures Will Include Change in Symptom Severity.

Description

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

Title

Secondary Outcome Measures Will Include Change in Quality of Life.

Description

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

Title

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)

Description

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

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

No

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: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Linda A Nguyen

Organizational Affiliation

Stanford University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Pankaj Jay Pasricha

Organizational Affiliation

Stanford University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford University School of Medicine

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

9824125

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. doi: 10.1023/a:1026665728213.

Results Reference

background

PubMed Identifier

12539997

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.

Results Reference

background

PubMed Identifier

11596661

Citation

Stacher G. Diabetes mellitus and the stomach. Diabetologia. 2001 Sep;44(9):1080-93. doi: 10.1007/s001250100619. Erratum In: Diabetologia 2002 Feb;45(2):293.

Results Reference

background

PubMed Identifier

17347455

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.

Results Reference

background

PubMed Identifier

14681545

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.

Results Reference

background

PubMed Identifier

1767961

Citation

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

Results Reference

background

Gastroparesis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial