- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01334229
Sitagliptin and Kinetics of Triglyceride-rich Lipoproteins Apolipoprotein B48 and B100 in Patients With Type 2 Diabetes (JANUB48)
March 7, 2016 updated by: Patrick Couture, Laval University
A Randomized, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Effects of Sitagliptin on the Kinetics of Triglyceride-rich Lipoproteins Apolipoprotein B48 and Apolipoprotein B100 in Patients With Type 2 Diabetes
Sitagliptin is a potent and selective inhibitor of dipeptidyl peptidase IV (DPP-IV), and has been shown to reduce fasting and postprandial glucose levels in patients with type 2 diabetes mainly through incretin hormone-mediated improvements in islet function [13].
Although clinical studies to date indicate that fasting lipid levels are minimally affected by DPP-IV inhibitor treatment [14-16], animal studies suggested that DPP-IV inhibition reduce intestinal triglycerides (TG) absorption and apolipoprotein (apo) production [17] and increased chylomicron catabolism [18].
Interestingly, a recent study supporting this hypothesis showed that vildagliptin therapy was able to reduce postprandial intestinal triglyceride-rich lipoproteins (TRL) particles in patients with type 2 diabetes [19].
Recently, our group has reported that sitagliptin treatment significantly reduced plasma apo B-48 and TG concentrations in the postprandial state.
Moreover, animal studies showed that sitagliptin decreased intestinal secretion of intestinal apo B-48, mainly by increasing level of glucagon-like peptide (GLP)-1 [20].
Therefore, the present study was designed to examine the effects of sitagliptin on the kinetics of TRL apo B-48 and in patients with type 2 diabetes.
A possible reduction in postprandial atherogenic TRL apo B-48-containing lipoprotein levels by sitagliptin would add to therapeutic utility of this DPP-4 inhibitor and suggest the potential to reduce cardiovascular risk in patients with type 2 diabetes.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
22
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Quebec, Canada, G1V 0A6
- Laval University
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Placebo for 6 weeks
|
Placebo for 6 weeks
|
Experimental: Sitagliptin
Sitagliptin 100 mg/d for 6 weeks
|
Sitagliptin 100 mg/d for 6 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Measurement of Apolipoprotein B48 and Apolipoprotein B100 Production Rates With Stable Isotope During Postprandial Period
Time Frame: 6 weeks
|
6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Measurement of Glucagon-like Peptide-1 by ELISA
Time Frame: 6 weeks
|
6 weeks
|
Measurement of Glucose
Time Frame: 6 weeks
|
6 weeks
|
Measurement of Insulin
Time Frame: 6 weeks
|
6 weeks
|
Measurement of Apolipoprotein B48 and Apolipoprotein B100 Pool Sizes With Stable Isotope During Postprandial Period
Time Frame: 6 weeks
|
6 weeks
|
Measurement of Apolipoprotein B48 and Apolipoprotein B100 Fractional Catabolic Rates With Stable Isotope During Postprandial Period
Time Frame: 6 weeks
|
6 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Patrick Couture, MD, PhD, Laval University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2011
Primary Completion (Actual)
March 1, 2013
Study Completion (Actual)
December 1, 2013
Study Registration Dates
First Submitted
April 11, 2011
First Submitted That Met QC Criteria
April 12, 2011
First Posted (Estimate)
April 13, 2011
Study Record Updates
Last Update Posted (Estimate)
April 4, 2016
Last Update Submitted That Met QC Criteria
March 7, 2016
Last Verified
March 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Protease Inhibitors
- Incretins
- Dipeptidyl-Peptidase IV Inhibitors
- Sitagliptin Phosphate
Other Study ID Numbers
- IIS#39262
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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