Impact of Sitagliptin on Cardiovascular Exercise Performance in Type 2 Diabetes
The goal of this study is to examine whether sitagliptin, an agent which enhances the action of hormones that control the release of insulin and is already in clinical use for type 2 diabetes, might also improve functional exercise capacity.
1. To test whether sitagliptin will improve functional exercise capacity in persons with type 2 diabetes compared to glimepiride.
1a. The primary outcome will be peak oxygen consumption (VO2peak) and oxygen uptake kinetics (VO2 kinetics).
1b. Secondary outcomes include cardiac function, endothelial function and tissue oxygen saturation (STO2) as well as health-related quality of life.
2. To evaluate the impact of sitagliptin on muscle mitochondrial function 2a. The primary outcome to address this aim will be 31P measurements (phosphocreatine, free inorganic phosphate, adenosine triphosphate peaks, adenosine diphosphate and pH)
Impact: Novel approaches are needed to decrease excess cardiovascular morbidity and mortality in diabetes. Diabetes impairs cardiovascular fitness and thereby mortality. A demonstration that sitagliptin improves cardiovascular fitness, (and possibly mitochondrial function) will provide important new data pertinent to the management of diabetes and pre-diabetes.
|Type 2 Diabetes Cardiovascular Disease||Drug: Sitagliptin Drug: Glimepiride Drug: Placebo|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
|Official Title:||Impact of Sitagliptin on Cardiovascular Exercise Performance in Type 2 Diabetes|
- One primary outcome will be change in peak oxygen consumption (VO2peak). [ Time Frame: 3 months ]Subjects' peak oxygen consumption will be tested on a stationary bike before and after 3 months of study medication.
- Changes from baseline in 31P measurement: phosphocreatine [ Time Frame: 3 months ]Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment
- One primary outcome will be oxygen uptake kinetics (VO2 kinetics) [ Time Frame: 3 months ]Oxygen uptake kinetics will be tested on a stationary bike before and after 3 months of study medication.
- Changes from baseline in 31P measurement: free Pi [ Time Frame: 3 months ]Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment
- Changes from baseline in 31P measurement: adenosine triphosphate (ATP) peaks [ Time Frame: 3 months ]Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment
- Changes from baseline in 31P measurement: adenosine diphosphate (ADP) [ Time Frame: 3 months ]
- Changes from baseline in 31P measurement: pH [ Time Frame: 3 months ]
- Changes 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
- 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
- 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.
|Study Start Date:||October 2013|
|Estimated Study Completion Date:||June 2018|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: Sitagliptin plus placebo
100 mg sitagliptin plus 2 mg placebo once daily for three months
100 mg sitagliptin
Other Name: Januvia (sitagliptin)Drug: Placebo
2 mg placebo once daily
Other Name: Placebo 1-sitagliptin
Active Comparator: Glimepiride plus placebo
2 mg glimepiride plus 100 mg placebo once daily for three months
Other Name: AmarylDrug: Placebo
100 mg placebo once daily for three months
Other Name: Placebo 2- glimepiride
Subjects will come for a total of nine testing visits during which evaluations will take place. Visits are structured as follows:
- After subjects review the study and give consent for study participation, a history and physical exam will be performed. Ankle brachial index, autonomic nervous system function tests, the Low-level Physical Activity Recall questionnaire and vital signs will be performed.
- Blood drawn for measurement of hemoglobin A1C, fasting glucose, fasting insulin, free fatty acids and microalbuminuria, c-reactive protein, interleukin 6, adiponectin, and creatinine and glycerol. Additional screening labs include complete blood count (CBC), follicle-stimulating hormone, urine protein and a lipid panel to assess whether women are pre- or post-menopausal (FSH), and overall health (CBC, lipids and urine protein). A dietary survey will be administered for food preferences for the three day study diet administered prior to visits 3-5 and 7-9. Dual-energy xray absorptiometry (DEXA) and body composition tests will be done to ensure that groups are weight similar (using fat-free mass). A pulmonary function test, 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. A graded exercise test will be done to determine the VO2peak. Patients will have measures of cardiac function and endothelial function on visit 3 by plethysmography and cardiac echo. Vital signs will be taken at rest.
- Subjects will receive a three day study diet prior to visit 4. Calf muscle magnetic resonance spectroscopy (MRS) will be performed on a 3.0 T whole-body MRI scanner.
- During visit 5, arterial stiffness/endothelial function will be non-invasively measured by the Sphygmocor system. Subjects will also have three constant-load tests to measure 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 taking sitagliptin plus placebo or glimepiride plus placebo and all must be taking metformin (1-2 grams /d) for 3 months. Sitagliptin and its placebo will be administered 100 mg/d. Glimepiride and its placebo will be administered 2 mg/day. During the treatment phase subjects will be given a log to keep track of their blood glucose each day.
- Visit 6 will consist of a physical exam with a clinician as well as a blood draw and check of vital signs during sitagliptin or glimepiride treatment.
- After 3 months of sitagliptin or glimepiride administration, Visit 3 will be repeated. Additional testing to be performed during visit 7 will include a physical exam performed by a study physician, blood work for covariate lab tests listed in Visit 2 and the Low-level Physical Activity Recall(LoPAR) questionnaire.
- During visit 8, visit 4 procedures will be repeated.
- During visit 9, the testing performed during visit 5 will be repeated.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01951339
|Contact: Deirdre Rafferty, MSemail@example.com|
|Contact: Ian Leavitt, MSfirstname.lastname@example.org|
|United States, Colorado|
|University of Colorado Anschutz Medical Campus||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Deirdre Rafferty 720-848-6688 email@example.com|
|Contact: Ian Leavitt 720-848-7103 firstname.lastname@example.org|
|Principal Investigator: Judith G. Regensteiner, PhD|
|Principal Investigator: Jane EB Reusch, MD|
|Principal Investigator:||Judith G. Regensteiner, PhD||University of Colorado - Anschutz Medical Campus|
|Principal Investigator:||Jane EB Reusch, MD||University of Colorado - Anschutz Medical Campus|