Impact of Exenatide on Cardiovascular Exercise Performance in Type 2 Diabetes
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, we 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. Our 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.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
|Official Title:||Impact of Exenatide on Cardiovascular Exercise Performance in Type 2 Diabetes|
- Change from baseline in peak oxygen consumption (VO2 peak) [ Time Frame: 3 months ] [ Designated as safety issue: No ]Subjects' peak oxygen consumption (VO2 peak) will be tested on a stationary bike before and after 3 months of study medication or placebo.
- Change from baseline in echocardiographic measures [ Time Frame: 3 months ] [ Designated as safety issue: No ]Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
- Change from baseline in oxygen uptake kinetics steady state tau [ Time Frame: 3 months ] [ Designated as safety issue: No ]Time to steady state oxygen consumption will be assessed in subject before and after 3 months of study medication or placebo.
- Change from baseline in arterial stiffness [ Time Frame: 3 months ] [ Designated as safety issue: No ]Arterial stiffness will be measured via sphygmocor before and after 3 months of study medication or placebo.
- Change from baseline in peak dilation of brachial artery diameter [ Time Frame: 3 months ] [ Designated as safety issue: No ]Change in the response of the brachial artery to hyperemia will be assessed before and after 3 months of study medication or placebo.
- Change in (non-invasively measured) deoxygenated hemoglobin concentration in the vastus lateralis during exercise [ Time Frame: 3 months ] [ Designated as safety issue: No ]Deoxygenated hemoglobin concentration will be measured using near-infrared spectroscopy during sub-maximal exercise before and after 3 months of study drug administration.
|Study Start Date:||October 2010|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Pre-dosed inject-able pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months
Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)
Other Name: Byetta
Placebo Comparator: 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
Subcutaneous injection 2.5 mcg-10 mcg BID
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01364584
|United States, Colorado|
|University of Colorado Anschutz Medical Campus|
|Aurora, Colorado, United States, 80045|
|Principal Investigator:||Judith G Regensteiner, PhD||University of Colorado, Denver|