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Sitagliptin Therapy and Kinetics of Inflammatory Markers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02536248
Recruitment Status : Completed
First Posted : August 31, 2015
Results First Posted : May 13, 2020
Last Update Posted : May 13, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Patrick Couture, Laval University

Tracking Information
First Submitted Date  ICMJE August 27, 2015
First Posted Date  ICMJE August 31, 2015
Results First Submitted Date  ICMJE March 30, 2020
Results First Posted Date  ICMJE May 13, 2020
Last Update Posted Date May 13, 2020
Actual Study Start Date  ICMJE August 1, 2015
Actual Primary Completion Date September 30, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2015)
Measurement of C-reactive Protein Production Rate With Stable Isotope During Postprandial Period [ Time Frame: 6 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2020)
  • Measurement of Serum Amyloid A Production Rate With Stable Isotope During Postprandial Period [ Time Frame: 6 weeks ]
  • Measurement of L-selectin Production Rate With Stable Isotope During Postprandial Period [ Time Frame: 6 weeks ]
  • Measurement of ICAM-1 Production Rate With Stable Isotope During Postprandial Period [ Time Frame: 6 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2015)
  • Measurement of L-selectin Production Rate With Stable Isotope During Postprandial Period [ Time Frame: 6 weeks ]
  • Measurement of ICAM-1 Production Rate With Stable Isotope During Postprandial Period [ Time Frame: 6 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sitagliptin Therapy and Kinetics of Inflammatory Markers
Official Title  ICMJE EFFECTS OF SITAGLIPTIN THERAPY ON THE KINETICS OF MARKERS OF LOW-GRADE INFLAMMATION AND CELL ADHESION MOLECULES IN PATIENTS WITH TYPE 2 DIABETES
Brief Summary Inflammatory processes are increasingly being recognized as a critical step in the pathogenesis of both diabetes and heart disease and may constitute a biological link between the two diseases. Inflammatory cytokines increase vascular permeability, change vasoregulatory responses, increase leukocyte adhesion to endothelium, and facilitate thrombus formation by inducing procoagulant activity, inhibiting anticoagulant pathways, and impairing fibrinolysis. Leukocyte adhesion to arterial endothelial cells is thought to be an important step in the development of atherosclerosis, and adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and L-selectin, play key roles in this process. Therefore, identifying novel therapeutic approaches that would favorably affect inflammation, endothelial function, and glucose is of significant interest. Investigators have recently demonstrated that, relative to placebo, sitagliptin treatment resulted in a significant reduction in plasma levels of various inflammatory markers and cell adhesion molecules. The results also suggest that the beneficial effects of sitagliptin on both inflammation and endothelial function are most likely mediated by an elevation in plasma GLP-1 levels and global improvement of the glucose-insulin homeostasis. However, the mechanisms underlying the beneficial effects of sitagliptin on these markers remain to be fully elucidated. The proposed study will address this key issue.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Type 2 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Sitagliptin
    Sitagliptin 100 mg/d for 6 weeks
    Other Name: Januvia
  • Drug: Placebo
    Placebo for 6 weeks
Study Arms  ICMJE
  • Experimental: Sitagliptin first, then Placebo

    Sitagliptin 100 mg/d for 6 weeks

    Wash-out 14 days

    Placebo for 6 weeks

    Interventions:
    • Drug: Sitagliptin
    • Drug: Placebo
  • Placebo Comparator: Placebo first, then Sitagliptin

    Placebo for 6 weeks

    Wash-out 14 days

    Sitagliptin 100 mg/d for 6 weeks

    Interventions:
    • Drug: Sitagliptin
    • 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: April 30, 2020)
20
Original Actual Enrollment  ICMJE
 (submitted: August 28, 2015)
22
Actual Study Completion Date  ICMJE October 31, 2017
Actual Primary Completion Date September 30, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males 18 to 65 years of age.
  • Post-menopausal women under age 65 on stable medical therapy for 6 months before the study (the patient should have demonstrated stable lipid panels)
  • Women should not be on hormone replacement therapy (no recent starting or stopping)
  • Type 2 diabetes as defined by the American Diabetes Association.
  • Non-smoker.
  • Body mass index between 25.0 and 40.0 kg/m2.
  • Baseline glycated hemoglobin A1c (HbA1c) between 6.5 and 8.5%.
  • Baseline fasting plasma glucose < 15.0 mmol/L.
  • Plasma triglyceride levels between 1.5 and 8.0 mmol/L (135 and 710 mg/dl) at screening and week -4.
  • Patients having received stable doses of metformin for at least 3 months before randomization.
  • Subjects must be willing to give written informed consent and able to adhere to dosing schedule, visit schedule and phone follow-up assessment.
  • Patients should be otherwise generally healthy, without elevations in hepatic transaminases or abnormal renal function or coagulation.
  • Patients having normal thyroid stimulating hormone at screening

Exclusion Criteria:

  • Patients with extreme dyslipidemias, such as familial hypercholesterolemia will be excluded.
  • Patients with type 1 diabetes, secondary form of diabetes or acute metabolic diabetic complications will be excluded.
  • Patients having received or being treated with insulin or a thiazolidinedione within the past 6 months will be excluded.
  • Patients taking any other hypoglycemic agent, other than metformin.
  • Subjects will be excluded if they have cardiovascular disease (coronary heart disease, cerebrovascular disease or peripheral arterial disease) or if they are taking other medications known to affect lipoprotein metabolism (e.g. steroids, beta blockers, thiazide diuretics, lipid lowering agents, significant alcohol intake etc.).
  • Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
  • Individuals with a history of mental instability, drug or alcohol abuse or individuals who have been treated or are being treated for severe psychiatric illness that, in the opinion of the investigator, may interfere with optimal participation in the study.
  • History of alcohol or drug abuse within the past 2 years. Patients must not take alcohol during the study.
  • Disorders of the hematologic, digestive, or central nervous systems, including cerebrovascular disease and degenerative disease, that would limit study evaluation or participation.
  • Known impairment of renal function (serum creatinine levels > 1.7 mg/dL for men), dysproteinemia, nephrotic syndrome, or other renal disease (24-hour urinary protein ≥3 ± 1 g).
  • Active or chronic hepatobiliary or hepatic disease. In addition, patients with aspartate aminotransferase or alanine aminotransferase >2 x upper limit of the laboratory reference range will be excluded.
  • Subjects with coagulopathy (prothrombin time or partial thromboplastin time at Visit 1 >1.5 times control).
  • Subjects with hemoglobin >2 x the lower limit of the laboratory reference range will be excluded.
  • Patients who are known to have tested positive for human immunodeficiency virus (HIV).
  • Patients who are currently enrolled in another clinical study.
  • Patients who have used any investigational drug within 30 days of the first clinic visit.
  • Congestive heart failure New York Heart Association (NYHA) Class III or IV. Uncontrolled cardiac arrhythmias within 3 months of study entry.
  • Uncontrolled diabetes mellitus (HbA1c>8.5%) or other endocrine or metabolic disease known to influence serum lipids or lipoproteins. Clinically euthyroid subjects on replacement doses of thyroid hormone are eligible for enrollment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 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 Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02536248
Other Study ID Numbers  ICMJE JANU-INF
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Patrick Couture, Laval University
Study Sponsor  ICMJE Laval University
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Patrick Couture, MD, PhD, FRCP Laval University
PRS Account Laval University
Verification Date April 2020

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