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| Sponsors and Collaborators: |
University of Vermont Merck |
|---|---|
| Information provided by: | University of Vermont |
| ClinicalTrials.gov Identifier: | NCT00732121 |
Purpose
Background:
Incretin hormones are hormones produced by the gut in response to food intake. These hormones help the body to control the metabolism of glucose (sugar).
In particular, two incretin hormones (GLP-1 and GIP) cause the pancreas to secrete more insulin in response to high blood glucose levels. This helps the body to metabolize the glucose more effectively, lowering blood sugar levels. In addition to their effects on the pancreas, GLP-1 and GIP have effects on other tissues, including the brain, gut, fat cells and bone. A new class of oral drugs developed for the treatment of type 2 diabetes mellitus (T2DM) called DPP-4 inhibitors increases levels of the active forms of GLP-1 and GIP in the body by preventing their breakdown. This study tests whether a medicine in this class called sitagliptin (Januvia), which is commonly used to treat T2DM, affects markers of bone turnover in patients with T2DM. The hypothesis is that treatment with sitagliptin will increase markers of bone formation and decrease markers of bone resorption during a mixed meal, by enhancing active circulating levels of GLP-1, GIP and GLP-2.
Methods:
To address this question we will recruit patients with T2DM whose diabetes is controlled with either diet+exercise or with metformin (another medicine commonly used to treat T2DM). Subjects will undergo measurement of body fat and bone mineral density by DEXA scanning and a 3-hour mixed meal test.
During the mixed meal test blood samples will be taken to measure how much GLP-1 and GIP are produced. Markers of bone formation will also be measured in blood samples obtained during the mixed meal test. Subjects will then be randomly assigned to 8 weeks of treatment with either sitagliptin (100 mg/day) or matching placebo (an inactive tablet that does not contain medication). Subjects will be seen 4 weeks after commencing treatment to assess safety and tolerability. After 8 weeks of treatment the meal test will be repeated. Subjects will then be washed off of their initial treatment (sitagliptin or placebo) for 1 week (that is, they will receive no study medication during this period). After the washout period, they will commence a second 8-week period of treatment with the other study medication (that is, if they received sitagliptin initially, they will receive placebo during period 2 and vice-versa). At the end of period 2, subjects will undergo a third mixed meal test with measurement of GLP-1, GIP and markers of bone turnover.
Significance:
Recent studies suggest that oral antidiabetic medications of the thiazolidinedione class, such as rosiglitazone (Avandia) and pioglitazone (Actos), may weaken bones, increasing the risk of fractures in older women with diabetes. The proposed study will test whether drugs of the DPP-4 inhibitor class, such as sitagliptin (Januvia), have beneficial effects on bone turnover by increasing the activity of GLP-1 and GIP. Results of this pilot study may suggest the need to perform longer-term studies to determine whether DPP-4 inhibitors increase bone mineral density and reduce the risk of fractures in patients with diabetes.
| Condition | Intervention | Phase |
|---|---|---|
|
Type 2 Diabetes |
Drug: Sitagliptin Drug: Placebo |
Phase IV |
| Study Type: | Interventional |
| Study Design: | Basic Science, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Efficacy Study |
| Official Title: | Effects of Sitagliptin On Markers of Bone Turnover in Patients With Type 2 Diabetes |
| Estimated Enrollment: | 20 |
| Study Start Date: | August 2008 |
| Estimated Study Completion Date: | September 2009 |
| Estimated Primary Completion Date: | September 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
1: Active Comparator
Sitagliptin
|
Drug: Sitagliptin
100 mg daily for 4 weeks
|
|
2: Placebo Comparator
Placebo arm
|
Drug: Placebo
Placebo
|
Eligibility| Ages Eligible for Study: | 18 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| Contact: Richard E Pratley, MD | 802-847-8901 | richard.pratley@uvm.edu |
| Contact: Rose Christian, MD | 802-847-4576 | rose.christian@vtmednet.org |
| United States, Vermont | |
| University of Vermont | Recruiting |
| South Burlington, Vermont, United States, 05403 | |
| Contact: Amy Prue, BA 802-847-8916 amy.prue@vtmednet.org | |
| Contact: Angela Ferro, RN 802-847-8908 angela.ferro@vtmednet.org | |
| Principal Investigator: | Richard E Pratley, MD | University of Vermont |
More Information
| Responsible Party: | University of Vermont College of Medicine ( Richard Pratley, MD ) |
| Study ID Numbers: | Merck-33283 |
| Study First Received: | August 7, 2008 |
| Last Updated: | February 12, 2009 |
| ClinicalTrials.gov Identifier: | NCT00732121 History of Changes |
| Health Authority: | United States: Food and Drug Administration |
|
Type 2 Diabetes |
|
Dipeptidyl-Peptidase IV Inhibitors Metabolic Diseases Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases |
Endocrinopathy Glucose Metabolism Disorders Metabolic Disorder Protease Inhibitors Sitagliptin |
|
Dipeptidyl-Peptidase IV Inhibitors Metabolic Diseases Molecular Mechanisms of Pharmacological Action Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases |
Enzyme Inhibitors Glucose Metabolism Disorders Pharmacologic Actions Protease Inhibitors Sitagliptin |
