Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Sitagliptin Drug: Placebo Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: EFFECTS OF SITAGLIPTIN THERAPY ON THE KINETICS OF MARKERS OF LOW-GRADE INFLAMMATION AND CELL ADHESION MOLECULES IN PATIENTS WITH TYPE 2 DIABETES
Actual Study Start Date : August 1, 2015
Actual Primary Completion Date : September 30, 2017
Actual Study Completion Date : October 31, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sitagliptin first, then Placebo

Sitagliptin 100 mg/d for 6 weeks

Wash-out 14 days

Placebo for 6 weeks

Drug: Sitagliptin
Sitagliptin 100 mg/d for 6 weeks
Other Name: Januvia

Drug: Placebo
Placebo for 6 weeks

Placebo Comparator: Placebo first, then Sitagliptin

Placebo for 6 weeks

Wash-out 14 days

Sitagliptin 100 mg/d for 6 weeks

Drug: Sitagliptin
Sitagliptin 100 mg/d for 6 weeks
Other Name: Januvia

Drug: Placebo
Placebo for 6 weeks




Primary Outcome Measures :
  1. Measurement of C-reactive Protein Production Rate With Stable Isotope During Postprandial Period [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. Measurement of Serum Amyloid A Production Rate With Stable Isotope During Postprandial Period [ Time Frame: 6 weeks ]
  2. Measurement of L-selectin Production Rate With Stable Isotope During Postprandial Period [ Time Frame: 6 weeks ]
  3. Measurement of ICAM-1 Production Rate With Stable Isotope During Postprandial Period [ Time Frame: 6 weeks ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02536248


Locations
Layout table for location information
Canada, Quebec
Laval University
Quebec City, Quebec, Canada, G1V 0A6
Sponsors and Collaborators
Laval University
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Principal Investigator: Patrick Couture, MD, PhD, FRCP Laval University
  Study Documents (Full-Text)

Documents provided by Patrick Couture, Laval University:
Study Protocol  [PDF] February 12, 2015
Statistical Analysis Plan  [PDF] February 12, 2015

Layout table for additonal information
Responsible Party: Patrick Couture, MD, PhD, FRCP, Laval University
ClinicalTrials.gov Identifier: NCT02536248    
Other Study ID Numbers: JANU-INF
First Posted: August 31, 2015    Key Record Dates
Results First Posted: May 13, 2020
Last Update Posted: May 13, 2020
Last Verified: April 2020
Keywords provided by Patrick Couture, Laval University:
sitagliptin
diabetes
inflammation
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action