Impact of Exenatide on Cardiovascular Exercise Performance in Type 2 Diabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Colorado, Denver
Sponsor:
Collaborators:
Amylin Pharmaceuticals, LLC.
Eli Lilly and Company
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01364584
First received: May 24, 2011
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Type 2 Diabetes
Drug: Exenatide
Drug: Placebo

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 30
Study Start Date: October 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide Drug: Exenatide
Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)
Other Name: Byetta
Placebo Comparator: Placebo Drug: Placebo
Subcutaneous injection 2.5 mcg-10 mcg BID

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.

  Eligibility

Ages Eligible for Study:   45 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01364584

Locations
United States, Colorado
University of Colorado Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Leah Herlache       leah.herlache@ucdenver.edu   
Principal Investigator: Judith G Regensteiner, PhD         
Sponsors and Collaborators
University of Colorado, Denver
Amylin Pharmaceuticals, LLC.
Eli Lilly and Company
Investigators
Principal Investigator: Judith G Regensteiner, PhD University of Colorado, Denver
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01364584     History of Changes
Other Study ID Numbers: 10-0438
Study First Received: May 24, 2011
Last Updated: May 20, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 18, 2014