Study of the Effect of Sitagliptin on Glucose (Sugar) Metabolism in Patients With Heart Failure

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Michael Fowler, Stanford University
ClinicalTrials.gov Identifier:
NCT00657280
First received: April 9, 2008
Last updated: December 23, 2013
Last verified: December 2013
  Purpose

This study will investigate the effects of sitagliptin, a medicine commonly used to treat type 2 diabetes, on the utilization of glucose by the heart in patients with heart failure which is not due to heart attacks. We hope to determine whether improving the heart's ability to use glucose in the blood may help improve the function of the heart as well. If so, this may suggest that even people who do not have frank diabetes but who do have heart failure may benefit from using this medication.

This study will also investigate the effect of sitagliptin on the body's use of sugar, and of the effect of sitagliptin on blood flow to the heart.


Condition Intervention
Heart Failure, Congestive
Drug: Sitagliptin

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Effect of Sitagliptin on Insulin Resistance and Myocardial Metabolism in Heart Failure

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Determine the effects of sitagliptin on myocardial glucose uptake in patients with nonischemic cardiomyopathy [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    This study will investigate the effects of sitagliptin, a medicine commonly used to treat type 2 diabetes, on the utilization of glucose by the heart in patients with heart failure which is not due to heart attacks. We hope to determine whether improving the heart's ability to use glucose in the blood may help improve the function of the heart as well. If so, this may suggest that even people who do not have frank diabetes but who do have heart failure may benefit from using this medication.

  • Determine the effects of sitagliptin on myocardial glucose uptake in patients with nonischemic cardiomyopathy [ Time Frame: 2008-2012 ] [ Designated as safety issue: No ]
    This study will investigate the effects of sitagliptin, a medicine commonly used to treat type 2 diabetes, on the utilization of glucose by the heart in patients with heart failure which is not due to heart attacks. We hope to determine whether improving the heart's ability to use glucose in the blood may help improve the function of the heart as well. If so, this may suggest that even people who do not have frank diabetes but who do have heart failure may benefit from using this medication.


Secondary Outcome Measures:
  • Determine the effects of sitagliptin on microvascular function in patients with nonischemic cardiomyopathy [ Time Frame: 2010-2012 ] [ Designated as safety issue: Yes ]
  • Determine the effects of sitagliptin on microvascular function in patients with nonischemic cardiomyopathy [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    This study will investigate the effects of sitagliptin, a medicine commonly used to treat type 2 diabetes, on the utilization of glucose by the heart in patients with heart failure which is not due to heart attacks. We hope to determine whether improving the heart's ability to use glucose in the blood may help improve the function of the heart as well. If so, this may suggest that even people who do not have frank diabetes but who do have heart failure may benefit from using this medication.


Enrollment: 16
Study Start Date: April 2008
Study Completion Date: February 2012
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: sugar pill
double blinded
Drug: Sitagliptin
Double blinded
Other Name: Merck

Detailed Description:

Screening:

Patients will be screened based on existing clinic information regarding NYHA class and heart failure characteristics. Patients will be approached in clinic after completing clinical care for that visit regarding participation in this trial.

If the patient agrees to participate, informed consent will be obtained at this time.

At enrollment:

Patients will be queried as to whether they have undergone previous nuclear medicine scans in the previous year in order to ensure that they do not exceed current standards for total annual radiation exposure.

Undergo a baseline combined 18-FDG PET/13N-NH3 PET/CT to assess the heart's ability to utilize blood sugar and coronary blood flow. This will take approximately 3-4 hours. This is a nuclear medicine procedure which is commonly used to assess myocardial viability as well as global heart function. It involves injection of a radioisotope-labeled tracers (18-FDG and 13N-NH3) intravenously followed by the measurement of myocardial uptake using a tomographic scanner. Venous blood samples performed during a 75g oral glucose load during the 18-FDG portion will assist with quantitation of myocardial glucose uptake and of measurements of insulin sensitivity. Perfusion (13N-NH3) images will be repeated during infusion of adenosine 0.14 mg/kg/min in order to assess coronary flow reserve. A computed tomography scan will be performed at the same time as the baseline PET scan for attenuation correction. Blood draws to measure changes in fasting insulin, blood sugar, lipid profile, and ADMA levels. Approximately 45 cc or 3 tablespoons of blood will be drawn and saved for possible future analysis.

18-FDG/13N-NH3 PET scans are routinely performed on patients with ischemic heart disease. While this study will use standard protocol for these examinations, they are not currently part of standard of care for nonischemic heart failure. However, they are important in testing the hypothesis of this study.

3) Begin sitagliptin 100 mg daily for four weeks. If calculated creatinine clearance is 30-49 cc/min by the Cockcroft-Gault formula, sitagliptin dose will be reduced to 50 mg daily for four weeks as per manufacturer guidelines. There will be no placebo arm. This will be an open-label study. Patients will be advised regarding potential side effects to prompt notification of study personnel. They will be instructed to contact the investigators for any concerns or evidence of adverse effects.

4) At four weeks: Repeat FDG/NH3 PET as above to compare to pretreatment scan. This will take approximately 3-4 hours. Blood draws to measure changes in fasting insulin, blood sugar, lipid profile, and ADMA levels. Approximately 45 cc or 3 tablespoons of blood will be drawn and saved for possible future analysis.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of nonischemic dilated cardiomyopathy, current NYHA class I-III congestive heart failure
  2. Treatment with a stable comprehensive heart failure regimen for at least 3 months (including beta-blockers and ACE-inhibitors or angiotensin receptor blockers unless intolerant)
  3. Age > 18 yrs

Exclusion Criteria:

  1. Cardiomyopathy primarily due to one of the following:

    1. Ischemic heart disease
    2. Primary valvular lesion
    3. Hypertrophic cardiomyopathy
  2. Cardiac resynchronization within the last 3 months
  3. Calculated creatinine clearance <30 ml/min or end-stage renal disease on dialysis. Creatinine clearance will be determined by the Cockcroft-Gault formula.
  4. Diagnosis of diabetes mellitus by:

    1. Diabetes previously diagnosed per patient history
    2. 2 or more fasting glucose values > 125 mg/dl
  5. History of heart transplantation
  6. Pregnancy or active breast feeding
  7. Hospitalization for decompensated heart failure within 30 days prior to enrollment.
  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: NCT00657280

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Michael B Fowler Stanford University
Study Director: Ronald M. Witteles MD Stanford University
  More Information

No publications provided

Responsible Party: Michael Fowler, PI, Stanford University
ClinicalTrials.gov Identifier: NCT00657280     History of Changes
Other Study ID Numbers: SU-04082008-1088, 11784 (Human Subjects)
Study First Received: April 9, 2008
Last Updated: December 23, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on October 29, 2014