Impact of Sitagliptin on Cardiovascular Exercise Performance in Type 2 Diabetes

This study is currently recruiting participants.
Verified January 2014 by University of Colorado, Denver
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01951339
First received: September 19, 2013
Last updated: January 15, 2014
Last verified: January 2014

September 19, 2013
January 15, 2014
October 2013
October 2015   (final data collection date for primary outcome measure)
  • One primary outcome will be change in peak oxygen consumption (VO2peak). [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment
  • Changes from baseline in 31P measurement: pH [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment
Same as current
Complete list of historical versions of study NCT01951339 on ClinicalTrials.gov Archive Site
  • Changes 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
  • 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
  • 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.
Same as current
Not Provided
Not Provided
 
Impact of Sitagliptin on Cardiovascular Exercise Performance in Type 2 Diabetes
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.

Specific aims:

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.

Subjects will come for a total of nine testing visits during which evaluations will take place. Visits are structured as follows:

  1. 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.
  2. 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.
  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. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. During visit 8, visit 4 procedures will be repeated.
  9. During visit 9, the testing performed during visit 5 will be repeated.
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
  • Type 2 Diabetes
  • Cardiovascular Disease
  • Drug: Sitagliptin
    100 mg sitagliptin
    Other Name: Januvia (sitagliptin)
  • Drug: Glimepiride

    Active Comparator

    2mg glimepiride

    Other Name: Amaryl
  • Drug: Placebo
    2 mg placebo once daily
  • Drug: Placebo
    100 mg placebo once daily for three months
  • Experimental: Sitagliptin plus placebo
    100 mg sitagliptin plus 2 mg placebo once daily for three months
    Interventions:
    • Drug: Sitagliptin
    • Drug: Placebo
  • Active Comparator: Glimepiride plus placebo
    2 mg glimepiride plus 100 mg placebo once daily for three months
    Interventions:
    • Drug: Glimepiride
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
28
December 2015
October 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Female subjects may be pre, peri or post-menopausal.
  2. People who do not participate in a regular exercise program (> one bout of exercise per week).
  3. Presence of type 2 diabetes will be documented by chart review that will confirm the diagnosis as well as the presence of treatment for diabetes.
  4. Persons with type 2 diabetes will be accepted for study only if they have total glycosylated hemoglobin levels (HbA1C) between 7.5 and 9.5% (adequate control) on therapy.
  5. Persons who are taking metformin 1-2 g/day only to control their type 2 diabetes (T2D).

Exclusion Criteria:

  1. Females of childbearing potential who are pregnant, planning to become pregnant or breastfeeding.
  2. Persons will be excluded if they have evidence of ischemic heart disease by history or abnormal resting or exercise electrocardiogram (EKG) (> 1 mm ST segment depression), regional wall motion abnormalities, left ventricular systolic dysfunction or significant valvular disease.
  3. Persons with angina or any other cardiac or pulmonary symptoms potentially limiting exercise performance.
  4. Presence of systolic blood pressure >190 at rest or >250 with exercise or diastolic pressure >95 at rest or >115 with exercise.
  5. Subjects who have peripheral arterial disease.
  6. Subjects with proteinuria (urine protein >200 mg/dl) or a creatinine > 2 mg/dl, suggestive of renal disease.
  7. Persons with liver function impairment defined as elevated liver function tests three times the upper limit.
  8. Persons with a history of pancreatitis.
  9. Subjects more than 140% of ideal body weight.
  10. Patients on insulin therapy will not be included.
  11. Current smokers will not be accepted for study since smoking can impair cardiovascular exercise performance but people who have quit smoking for at least 1year will be accepted for study.
  12. Persons with autonomic dysfunction (>20 mm fall in upright blood pressure without a change in heart rate) will be excluded.
  13. Diabetic persons with clinically evident distal symmetrical neuropathy will be excluded from further study, because of possible effects on exercise performance, by evaluation of symptoms (numbness, paresthesia) and signs (elicited by vibration, pinprick, light touch, ankle jerks).
  14. Persons with diabetic ketoacidosis.
  15. Persons with a serious hypersensitivity to sitagliptin, sulfonylureas or sulfonamides.
  16. Inability to walk or ride a bike unassisted for a continuous 5 minutes.
  17. Subjects will be excluded if they have any implanted metal in their body.
  18. Subjects currently being treated with Digoxin.
Both
22 Years to 70 Years
No
Contact: Shawna McMillin, MS 720-848-6689 shawna.mcmillin@ucdenver.edu
Contact: Leah Herlache, MS 303-724-2255 leah.herlache@ucdenver.edu
United States
 
NCT01951339
13-2015
No
University of Colorado, Denver
University of Colorado, Denver
Merck Sharp & Dohme Corp.
Principal Investigator: Judith G. Regensteiner, PhD University of Colorado Anschutz Medical Campus
Principal Investigator: Jane EB Reusch, MD University of Colorado Anschutz Medical Campus
University of Colorado, Denver
January 2014

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