Impact of Exenatide on Cardiovascular Exercise Performance in Type 2 Diabetes

NCT ID: NCT01364584

Last Updated: 2023-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2014-12-31

Brief Summary

Previous research in our lab and others has established that type 2 diabetes (T2D) is associated with significantly impaired functional exercise capacity, a factor which is potentially associated with an increased risk of cardiovascular disease in those with type 2 diabetes. Of great concern, the majority of people with type 2 diabetes are sedentary and one possible reason may be that exercise, even at low levels, is perceived as being a harder effort than for nondiabetic people. Thus, treatments that may motivate patients with type 2 diabetes to be more physically active have great potential benefit.

Recent observational studies suggest that glucagon-like peptide-1 agents, such as exenatide, may have a beneficial effect on endothelial and cardiac function. Because these two factors have been shown to be associated with exercise dysfunction in type 2 diabetes, the investigators hypothesize that exenatide may improve exercise capacity in those with type 2 diabetes. The aims of this study are to (1) assess whether exenatide will improve functional exercise capacity in persons with type 2 diabetes and (2) investigate the effect of exenatide on specific metabolic, endothelial, cardiac and peripheral circulatory measures of function related to changes in exercise capacity. The Investigators primary hypothesis is that exenatide will improve functional exercise capacity in people with type 2 diabetes. Having a drug that improves exercise capacity could motivate patients to exercise more and hence be a significant benefit.

Detailed Description

Subjects will come for a total of seven testing visits, including two screening visits, during which evaluations will take place. Visits are structured as follows:

Visits 1, 2 and 3 will be completed over a four-week period.

1. After subjects review the study and give consent for study participation, a history and physical exam will be performed. In addition, the Low-level Physical Activity Recall (LoPAR) questionnaire, pulmonary function testing, and vital signs will be performed.

2. Subjects will be asked to fast prior to visit 2. Blood and urine samples will be collected for measurement of glycosylated hemoglobin(HbA1C), fasting glucose, fasting insulin, free fatty acids and microalbuminuria (these measures will be covariates in the analyses). A dietary survey will be administered for food preferences for the three day study diet administered prior to visits 3, 4, 6 and 7. Dual Energy X-ray Absorptiometry (DXA) and body composition tests will be done to ensure that groups are weight similar (using fat-free mass). Autonomic nervous system testing, a resting electrocardiogram (EKG) and familiarization bicycle test will be performed.

3. Subjects will receive a three day study diet prior to visit 3. A resting and exercise EKG will be performed on the day of the visit. Patients will have measures made of cardiac function and endothelial function on visit 3 as well using plethysmography and cardiac echo. The peak aerobic capacity (VO2max) test will be performed. Vital signs will be taken at rest.

4. Randomization: Subjects will receive a three day study diet prior to visit 4. During visit four, arterial stiffness/endothelial function will be non-invasively measured by the Sphygmocor system. Subjects will have three constant-load tests to measure oxygen (VO2) kinetics where oxygen saturation (StO2) will be measured during exercise. A resting and exercise EKG and vital signs will be performed during the visit. Subjects will be randomized to either taking exenatide or placebo and all must have been taking metformin (1-2 grams /d) for at least 3 months. Exenatide will be titrated starting at 5 mcg twice per day for two weeks then moving to 10 mcg twice per day as tolerated and the placebo dose will match this titration. During the treatment phase subjects will be given a log to keep track of their blood glucose each day. Study coordinators will contact each subject weekly to obtain these values which will be checked by the study doctors and shared with the subject's primary care physician if adjustments in other medications need to be made.

5. Week 4: Visit 5 will consist of a physical exam with a clinician as well as a blood draw and check of vital signs during exenatide treatment.

6. Week 12: After 3 months of exenatide or placebo administration, the procedures of Visit 3 will be repeated as Visit 6. Additional testing to be performed during visit 6 include a physical exam performed by a study physician, DXA scan and body composition tests to monitor any changes in body composition (fat-free mass), blood work for lab tests listed in Visit 2 and the LoPAR questionnaire.

7. Week 13: During visit 7, the testing performed during visit 4 will be repeated after 3 months of exenatide or placebo administration.

Subjects will continue exenatide or placebo treatment while completing exit testing during Weeks 12 and 13.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Exenatide

Pre-dosed inject-able pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months

Group Type: EXPERIMENTAL

Exenatide

Intervention Type: DRUG

Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)

Placebo

Pre-dosed inject-able pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subcutaneous injection 2.5 mcg-10 mcg BID

Interventions

Exenatide

Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)

Intervention Type: DRUG

Placebo

Subcutaneous injection 2.5 mcg-10 mcg BID

Intervention Type: DRUG

Other Intervention Names

Byetta

Eligibility Criteria

Inclusion Criteria

• Men and women between the ages of 45 and 70 years of age
• Diagnosed with uncomplicated type 2 diabetes
• Sedentary persons (exercising not more than one time per week)
• Females who are post-menopausal
• BMI must be less than 35
• Subjects must be taking metformin for diabetes control and may also be on sulfonylurea drugs or meglitinides
• Glycosylated hemoglobin (HbA1C) <9%
• Non-smokers or former smokers who have quit for at least 1 year
• Absence of comorbid conditions
• Resting systolic blood pressure < 190, Resting diastolic blood pressure < 95

Exclusion Criteria

• People with type 2 diabetes (T2D) taking oral medications, other than metformin or sulfonylurea drugs or meglitinides, to control their diabetes.
• Persons treated with insulin will be excluded
• People who are currently smoking or have not quit for at least one year
• Peripheral neuropathy
• Regional wall motion abnormalities
• Left ventricular systolic dysfunction
• Ischemic heart disease (abnormal resting or exercise electrocardiogram)
• Presence of angina that would limit exercise performance
• Pulmonary problems that would limit exercise performance
• Systolic blood pressure >190 mmHg at rest or >250 mmHg with exercise or diastolic pressure >95 mmHg at rest or >115 mmHg with exercise
• Persons with autonomic dysfunction (>20 mm fall in upright BP without a change in heart rate)
• Proteinuria (urine protein >200 mg/dl) or a creatinine > 2.0 mg/dl
• Renal disease
• Persons with peripheral arterial disease
• Persons with a history of pancreatitis

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amylin Pharmaceuticals, LLC.

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith G Regensteiner, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Countries

United States

Other Identifiers

10-0438

Identifier Type: -

Identifier Source: org_study_id