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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Alabama at Birmingham
Sponsor:
Information provided by (Responsible Party):
Amy H. Warriner, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01374568
First received: June 10, 2011
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Type 2 Diabetes Mellitus
Drug: sitagliptin
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, 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)

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Bone turnover, measured by osteocalcin, type I collagen cross-linked aminoterminal peptide in urine (Urine NTX), and bone-specific alkaline phosphatase will be lower in subjects treated with sitagliptin when compared to those treated with placebo. [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Further information regarding the effect of incretin hormones on bone is important for safety reasons (recent information linking thiazolidinediones with increased risk of fracture), but more importantly,to better understand the mechanism of bone changes seen in persons with T2DM. Further information is needed to help guide clinicians in charge of caring for the growing population of persons with T2DM at risk of many complications, including an increased risk of fracture.


Estimated Enrollment: 40
Study Start Date: July 2010
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: sitagliptin
Sitagliptin
Drug: sitagliptin
sitagliptin 100mg daily
Other Name: Januvia
Placebo Comparator: Placebo
Placebo
Other: Placebo
1 pill daily
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders 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
  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: NCT01374568

Contacts
Contact: Tammy Perkins, RN 205-934-4112
Contact: Kentress Davison 205-934-4112

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Kentress Davison    205-934-4112      
Contact: Tammy Perkins, RN    205-934-4112      
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Amy Warriner, MD University of Alabama at Birmingham
  More Information

No publications provided

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
Study First Received: June 10, 2011
Last Updated: September 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
Type 2 diabetes
sitagliptin
Januvia

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

ClinicalTrials.gov processed this record on October 20, 2014