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Changes in Bone Turnover With Increased Incretin Hormone Exposure (DRTC)

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ClinicalTrials.gov Identifier: NCT01374568
Recruitment Status : Terminated (Study closed by sponsor. Funding ended.)
First Posted : June 16, 2011
Results First Posted : May 31, 2017
Last Update Posted : July 24, 2017
Sponsor:
Information provided by (Responsible Party):
Amy H. Warriner, University of Alabama at Birmingham

Brief Summary:
The purpose of this study is to determine if the use of sitagliptin increases bone formation and reduces bone turnover in postmenopausal women with type 2 diabetes.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: sitagliptin Other: Placebo Phase 4

Detailed Description:

Patients with Type 2 Diabetes Mellitus (T2DM) are at an increased risk of fracture, despite having bone mineral density (BMD) similar to age and sex matched cohorts. Recent studies have indicated that changes in incretin (INtestinal seCRETion of INsulin) hormones in the setting of T2DM may play a role in bone metabolism. Two of these incretin hormones, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), have been shown to be involved in bone turnover regulation, in addition to their effect in increasing insulin secretion and decreasing glucagon secretion in a glucose-dependent manner. In addition, the rise in glucagon-like peptide-2 (GLP-2) in the postprandial state has been found to have a direct effect on reduced bone resorption in a non-fasting state and treatment with GLP-2 improved BMD in postmenopausal women. Due to their glucose lowering effects, incretins have been a therapeutic target for the treatment of T2DM through GLP-1 receptor analogs or inhibition of incretin metabolism via dipeptidyl peptidase 4 (DPP-4) inhibitors (i.e. sitagliptin). Inhibition of DPP-4 leads to an approximate doubling of GLP-1 and GIP levels but also leads to reduced breakdown of GLP-2.

Less is known about the effect of incretin-directed therapies, specifically sitagliptin, and bone metabolism. To our knowledge, two studies have looked at the direct effects of currently available incretin-directed therapies on bone metabolism. Exenatide (a GLP-1 analog) treatment of insulin resistant and type 2 diabetic rats resulted in osteogenic effects with increased osteocalcin levels following treatment. In a study of female non-diabetic Sprague-Dawley rats treated with pioglitazone, rosiglitazone, sitagliptin, vs. placebo, no significant change in bone mineral density was seen in the sitagliptin or placebo treated rats (compared to significant loss of bone mineral density in the TZD groups). Even fewer published studies are available evaluating changes in bone metabolism with the use of incretin hormones in humans. The majority of the human studies have been completed with GLP-2. These studies show a dose-dependent effect of GLP-2 on bone resorption and, preliminarily, show improved bone mineral density in postmenopausal women treated with GLP-2. However, the changes in incretin activity vary in persons with glucose intolerance and T2DM. Therefore, it is important to understand the potential effects of these medications on bone metabolism in persons prescribed these medications for treatment of their T2DM.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Health Services Research
Official Title: Changes in Bone Turnover With Increased Incretin Hormone Exposure (UAB Diabetes Research and Training Center Pilot and Feasibility Study)
Study Start Date : July 2010
Primary Completion Date : July 6, 2012
Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: sitagliptin
Sitagliptin
Drug: sitagliptin
sitagliptin 100mg daily
Other Name: Januvia
Placebo Comparator: Placebo
Placebo
Other: Placebo
1 pill daily



Primary Outcome Measures :
  1. Bone Turnover in Subjects Treated With Sitagliptin When Compared to Those Treated With Placebo. [ Time Frame: 8 weeks ]
    Bone turnover assessed using change in TRACP5b over 8 weeks of treatment.

  2. Bone Turnover in Subjects Treated With Sitagliptin When Compared to Those Treated With Placebo [ Time Frame: 8 WEEKS ]
    Bone turnover assessed using change in bone-specific alkaline phosphatase (BAP) over 8 weeks of treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Postmenopausal women (as defined by age >55 years old or amenorrhea for >1years)
  • Type 2 DM currently not on diabetes-specific medication(s) or treated with monotherapy of metformin or a sulfonylurea. Patients treated with insulin monotherapy will also be eligible if the total daily dose of insulin is <10units.
  • Hemoglobin A1c (HbA1c) of 6.5-9.0%

Exclusion Criteria:

  • Use of an incretin mimetic (i.e. exenatide), a DPP-4 inhibitor (i.e. sitagliptin, saxagliptin), a thiazolidinedione, or oral glucocorticoids in the 6 months prior to the study will not be eligible
  • Known osteoporosis or patients treated with an osteoporosis-specific medication (bisphosphonate, teriparatide) or estrogen (including Selective Estrogen Receptor Modulators (SERMs)) or those who anticipate imminent treatment with one of these medications will be excluded from the study
  • Chronic kidney disease (calculated GFR <30 ml/min) or a disease known to affect bone turnover (i.e. Paget Disease, Osteogenesis Imperfecta, HIV) will be excluded from the study.
  • History of pancreatitis

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): NCT01374568


Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Amy Warriner, MD University of Alabama at Birmingham

Responsible Party: Amy H. Warriner, Assistant Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01374568     History of Changes
Other Study ID Numbers: UAB F100317002
First Posted: June 16, 2011    Key Record Dates
Results First Posted: May 31, 2017
Last Update Posted: July 24, 2017
Last Verified: June 2017

Keywords provided by Amy H. Warriner, University of Alabama at Birmingham:
Type 2 diabetes
sitagliptin
Januvia

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hormones
Sitagliptin Phosphate
Gastric Inhibitory Polypeptide
Incretins
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Hypoglycemic Agents
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents