search
Back to results

Impact of Sitagliptin on Cardiovascular Exercise Performance in Type 2 Diabetes

Primary Purpose

Type 2 Diabetes, Cardiovascular Disease

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Sitagliptin
Glimepiride
Placebo
Placebo
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Type 2 Diabetes focused on measuring diabetes, type 2 diabetes, exercise, echo, heart, sitagliptin, glimepiride, cardiovascular

Eligibility Criteria

22 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 and 9.5% (adequate control) on therapy.
  5. Persons who are taking metformin 500-2000 mg/day only to control their T2D, but are not taking any other diabetes medication in addition to or instead of metformin.
  6. Persons not taking medication to control diabetes.

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.

Sites / Locations

  • University of Colorado Anschutz Medical Campus

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sitagliptin plus placebo

Glimepiride plus placebo

Arm Description

100 mg sitagliptin plus 2 mg placebo once daily for three months

2 mg glimepiride plus 100 mg placebo once daily for three months

Outcomes

Primary Outcome Measures

Peak Oxygen Consumption (VO2peak).
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 Constant
Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment
Change in Oxygen Uptake Kinetics (VO2 Kinetics)
Oxygen uptake kinetics will be tested on a stationary bike before and after 3 months of study medication. VO2 kinetics is reported as the time constant associated with the change in oxygen update from rest to steady state.
Changes From Baseline in 31P Measurement: Free Pi Time Constant
Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment. Data are represented as the change in Pi through the scan.
Changes From Baseline in 31P Measurement: Adenosine Triphosphate (ATP) Peaks
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 Constant
Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment
Changes From Baseline in 31P Measurement: pH
Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment

Secondary Outcome Measures

Changes From Baseline in Echocardiographic Measures (Stroke Volume)
Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication
Change in (Non-invasively Measured) Deoxygenated Hemoglobin Concentration in the Vastus Lateralis During Exercise
Deoxygenated hemoglobin concentration will be measured using near-infrared spectroscopy during sub-maximal exercise before and after 3 months of study drug administration.

Full Information

First Posted
September 19, 2013
Last Updated
July 10, 2023
Sponsor
University of Colorado, Denver
Collaborators
Merck Sharp & Dohme LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT01951339
Brief Title
Impact of Sitagliptin on Cardiovascular Exercise Performance in Type 2 Diabetes
Official Title
Impact of Sitagliptin on Cardiovascular Exercise Performance in Type 2 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
October 2013 (Actual)
Primary Completion Date
June 2018 (Actual)
Study Completion Date
June 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes, Cardiovascular Disease
Keywords
diabetes, type 2 diabetes, exercise, echo, heart, sitagliptin, glimepiride, cardiovascular

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sitagliptin plus placebo
Arm Type
Experimental
Arm Description
100 mg sitagliptin plus 2 mg placebo once daily for three months
Arm Title
Glimepiride plus placebo
Arm Type
Active Comparator
Arm Description
2 mg glimepiride plus 100 mg placebo once daily for three months
Intervention Type
Drug
Intervention Name(s)
Sitagliptin
Other Intervention Name(s)
Januvia (sitagliptin)
Intervention Description
100 mg sitagliptin
Intervention Type
Drug
Intervention Name(s)
Glimepiride
Other Intervention Name(s)
Amaryl
Intervention Description
Active Comparator 2mg glimepiride
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo 1-sitagliptin
Intervention Description
2 mg placebo once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo 2- glimepiride
Intervention Description
100 mg placebo once daily for three months
Primary Outcome Measure Information:
Title
Peak Oxygen Consumption (VO2peak).
Description
Subjects' peak oxygen consumption will be tested on a stationary bike before and after 3 months of study medication.
Time Frame
Pre-intervention (Baseline) and post-intervention (3 months)
Title
Changes From Baseline in 31P Measurement: Phosphocreatine Time Constant
Description
Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment
Time Frame
Pre-intervention (Baseline) and post-intervention (3 months)
Title
Change in Oxygen Uptake Kinetics (VO2 Kinetics)
Description
Oxygen uptake kinetics will be tested on a stationary bike before and after 3 months of study medication. VO2 kinetics is reported as the time constant associated with the change in oxygen update from rest to steady state.
Time Frame
Pre-intervention (Baseline) and post-intervention (3 months)
Title
Changes From Baseline in 31P Measurement: Free Pi Time Constant
Description
Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment. Data are represented as the change in Pi through the scan.
Time Frame
Pre-intervention (Baseline) and post-intervention (3 months)
Title
Changes From Baseline in 31P Measurement: Adenosine Triphosphate (ATP) Peaks
Description
Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment
Time Frame
Pre-intervention (Baseline) and post-intervention (3 months)
Title
Changes From Baseline in 31P Measurement: Adenosine Diphosphate (ADP) Time Constant
Description
Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment
Time Frame
Pre-intervention (Baseline) and post-intervention (3 months)
Title
Changes From Baseline in 31P Measurement: pH
Description
Potential change in muscle mitochondrial function will be assessed after three months of study medication treatment
Time Frame
Pre-intervention (Baseline) and post-intervention (3 months)
Secondary Outcome Measure Information:
Title
Changes From Baseline in Echocardiographic Measures (Stroke Volume)
Description
Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication
Time Frame
Pre-intervention (Baseline) and post-intervention (3 months)
Title
Change in (Non-invasively Measured) Deoxygenated Hemoglobin Concentration in the Vastus Lateralis During Exercise
Description
Deoxygenated hemoglobin concentration will be measured using near-infrared spectroscopy during sub-maximal exercise before and after 3 months of study drug administration.
Time Frame
Pre-intervention (Baseline) and post-intervention (3 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
22 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female subjects may be pre, peri or post-menopausal. People who do not participate in a regular exercise program (> one bout of exercise per week). 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. Persons with type 2 diabetes will be accepted for study only if they have total glycosylated hemoglobin levels (HbA1C) between 7 and 9.5% (adequate control) on therapy. Persons who are taking metformin 500-2000 mg/day only to control their T2D, but are not taking any other diabetes medication in addition to or instead of metformin. Persons not taking medication to control diabetes. Exclusion Criteria: Females of childbearing potential who are pregnant, planning to become pregnant or breastfeeding. 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. Persons with angina or any other cardiac or pulmonary symptoms potentially limiting exercise performance. Presence of systolic blood pressure >190 at rest or >250 with exercise or diastolic pressure >95 at rest or >115 with exercise. Subjects who have peripheral arterial disease. Subjects with proteinuria (urine protein >200 mg/dl) or a creatinine > 2 mg/dl, suggestive of renal disease. Persons with liver function impairment defined as elevated liver function tests three times the upper limit. Persons with a history of pancreatitis. Subjects more than 140% of ideal body weight. Patients on insulin therapy will not be included. 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. Persons with autonomic dysfunction (>20 mm fall in upright blood pressure without a change in heart rate) will be excluded. 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). Persons with diabetic ketoacidosis. Persons with a serious hypersensitivity to sitagliptin, sulfonylureas or sulfonamides. Inability to walk or ride a bike unassisted for a continuous 5 minutes. Subjects will be excluded if they have any implanted metal in their body. Subjects currently being treated with Digoxin.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Judith G. Regensteiner, PhD
Organizational Affiliation
University of Colorado - Anschutz Medical Campus
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jane EB Reusch, MD
Organizational Affiliation
University of Colorado - Anschutz Medical Campus
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado Anschutz Medical Campus
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31182338
Citation
Scalzo RL, Rafferty D, Schauer I, Huebschmann AG, Cree-Green M, Reusch JEB, Regensteiner JG. Sitagliptin improves diastolic cardiac function but not cardiorespiratory fitness in adults with type 2 diabetes. J Diabetes Complications. 2019 Aug;33(8):561-566. doi: 10.1016/j.jdiacomp.2019.05.002. Epub 2019 May 10.
Results Reference
derived
Links:
URL
http://www.ucdenver.edu/academics/colleges/medicalschool/departments/medicine/GIM/ACTIVE/Pages/ACTIVE.aspx
Description
AcTIVe Research Lab

Learn more about this trial

Impact of Sitagliptin on Cardiovascular Exercise Performance in Type 2 Diabetes

We'll reach out to this number within 24 hrs