Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Bone Turnover in Type 2 Diabetes Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by University of Vermont.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
University of Vermont
ClinicalTrials.gov Identifier:
NCT00732121
First received: August 7, 2008
Last updated: June 25, 2010
Last verified: February 2009
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Sitagliptin On Markers of Bone Turnover in Patients With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by University of Vermont:

Primary Outcome Measures:
  • Change from baseline in the integrated response to the mixed meal test of markers of bone turnover following 8 weeks of treatment with sitagliptin vs. placebo. [ Time Frame: 8 weeks per subject ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in the active GIP in response to the mixed meal test [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in the active GLP-1 in response to the mixed meal test. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in the active GLP-2 in response to the mixed meal test. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in glucose response during the mixed meal test. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change in insulin secretion during the mixed meal test. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: August 2008
Estimated Study Completion Date: August 2010
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Sitagliptin
Drug: Sitagliptin
100 mg daily for 4 weeks
Other Name: Januvia (brand name for sitagliptin)
Placebo Comparator: 2
Placebo arm
Drug: Placebo
Placebo
Other Name: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes treated with diet/exercise or metformin
  • HbA1c less than or equal to 7%
  • Men and women aged 45-80 years old
  • If female, must be post-menopausal (natural or surgical)

Exclusion Criteria:

  • Endocrine disorders (acromegaly, anorexia, Cushings, type 2 diabetes, hyperparathyroidism, hyperthyroidism, hypercalcemia)
  • GI conditions (celiac sprue, gastric bypass/gastrectomy, active inflammatory bowel disease, cirrhosis)
  • Cancer (including multiple myeloma) within 3 years of the study (except local non-melanoma skin cancers and cervical carcinoma in situ)
  • Active alcoholism or drug abuse
  • Chronic kidney disease with a GFR < 60
  • HIV/AIDS
  • History of hypersensitivity reaction to sitagliptin or other DPP-4 inhibitors
  • Hemoglobin < 12 mg/dL for men and < 10 for women
  • Taking medications that could affect bone turnover (estrogen, progesterone, testosterone, bisphosphonates, SERMS, calcitonin, teriparatide cyclosporine glucocorticoids, methotrexate or phenothiazines), thiazolidinediones, sulfonylureas, dipeptidyl peptidase-4 inhibitors, exenatide, insulin, weight loss drugs
  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: NCT00732121

Locations
United States, Vermont
University of Vermont
South Burlington, Vermont, United States, 05403
Sponsors and Collaborators
University of Vermont
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Richard E Pratley, MD University of Vermont
  More Information

No publications provided

Responsible Party: Richard Pratley, MD, University of Vermont College of Medicine
ClinicalTrials.gov Identifier: NCT00732121     History of Changes
Other Study ID Numbers: Merck-33283
Study First Received: August 7, 2008
Last Updated: June 25, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Vermont:
Type 2 Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic 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 November 27, 2014