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Impact of Exenatide on Cardiovascular Exercise Performance in Type 2 Diabetes (Exenatide)

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ClinicalTrials.gov Identifier: NCT01364584
Recruitment Status : Completed
First Posted : June 2, 2011
Results First Posted : July 9, 2018
Last Update Posted : August 15, 2018
Sponsor:
Collaborators:
Amylin Pharmaceuticals, LLC.
Eli Lilly and Company
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE May 24, 2011
First Posted Date  ICMJE June 2, 2011
Results First Submitted Date  ICMJE June 29, 2017
Results First Posted Date  ICMJE July 9, 2018
Last Update Posted Date August 15, 2018
Study Start Date  ICMJE October 2010
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 4, 2018)
Peak Oxygen Consumption (VO2 Peak) [ Time Frame: Baseline and 3 months ]
Subjects' peak oxygen consumption (VO2 peak) will be tested on a stationary bike before and after 3 months of study medication or placebo.
Original Primary Outcome Measures  ICMJE
 (submitted: May 31, 2011)
Change from baseline in peak oxygen consumption (VO2 peak) [ Time Frame: 3 months ]
Subjects' peak oxygen consumption (VO2 peak) will be tested on a stationary bike before and after 3 months of study medication or placebo.
Change History Complete list of historical versions of study NCT01364584 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2018)
  • Oxygen Uptake Kinetics Steady State Tau [ Time Frame: Baseline and 3 months ]
    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: Baseline and 3 months ]
    Pulse wave velocity 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: Baseline and 3 months ]
    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: Baseline and 3 months ]
    Deoxygenated hemoglobin concentration will be measured using near-infrared spectroscopy during sub-maximal exercise before and after 3 months of study drug administration.
  • Echocardiographic Measures - Circumferential Strain [ Time Frame: Baseline and 3 months ]
    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
  • Echocardiographic Measures - Longitudinal Strain [ Time Frame: Baseline and 3 months ]
    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
  • Echocardiographic Measures - Stroke Volume [ Time Frame: Baseline and 3 months ]
    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
  • Echocardiographic Measures - Mitral Valve E Wave Velocity [ Time Frame: Baseline and 3 months ]
    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
  • Echocardiographic Measures - Mitral Valve E:A Wave Velocity [ Time Frame: Baseline and 3 months ]
    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
  • Echocardiographic Measures - Mitral Valve Deceleration Time [ Time Frame: Baseline and 3 months ]
    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
  • Echocardiographic Measures - Septal E' [ Time Frame: Baseline and 3 months ]
    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
  • Echocardiographic Measures - Septal E:E' [ Time Frame: Baseline and 3 months ]
    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
  • Echocardiographic Measures - Lateral E' [ Time Frame: Baseline and 3 months ]
    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
  • Echocardiographic Measures - Lateral E:E' [ Time Frame: Baseline and 3 months ]
    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2011)
  • Change from baseline in echocardiographic measures [ Time Frame: 3 months ]
    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 ]
    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 ]
    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 ]
    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 ]
    Deoxygenated hemoglobin concentration will be measured using near-infrared spectroscopy during sub-maximal exercise before and after 3 months of study drug administration.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Impact of Exenatide on Cardiovascular Exercise Performance in Type 2 Diabetes
Official Title  ICMJE Impact of Exenatide on Cardiovascular Exercise Performance in Type 2 Diabetes
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Condition  ICMJE Type 2 Diabetes
Intervention  ICMJE
  • Drug: Exenatide
    Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)
    Other Name: Byetta
  • Drug: Placebo
    Subcutaneous injection 2.5 mcg-10 mcg BID
Study Arms  ICMJE
  • Experimental: 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
    Intervention: Drug: Exenatide
  • 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
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 4, 2018)
23
Original Estimated Enrollment  ICMJE
 (submitted: May 31, 2011)
30
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 45 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01364584
Other Study ID Numbers  ICMJE 10-0438
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE
  • Amylin Pharmaceuticals, LLC.
  • Eli Lilly and Company
Investigators  ICMJE
Principal Investigator: Judith G Regensteiner, PhD University of Colorado, Denver
PRS Account University of Colorado, Denver
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP