Changes in Bone Turnover With Increased Incretin Hormone Exposure
Information source: University of Alabama at Birmingham
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Type 2 Diabetes Mellitus
Intervention: sitagliptin (Drug); Placebo (Other)
Phase: Phase 4
Status: Recruiting
Sponsored by: University of Alabama at Birmingham Official(s) and/or principal investigator(s): Amy Warriner, MD, Principal Investigator, Affiliation: University of Alabama at Birmingham
Overall contact: Tammy Perkins, RN, Phone: 205-934-4112
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.
Clinical Details
Official title: Changes in Bone Turnover With Increased Incretin Hormone Exposure (UAB Diabetes Research and Training Center Pilot and Feasibility Study)
Study design: Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Health Services Research
Primary outcome: 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.
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
Minimum age: 45 Years.
Maximum age: N/A.
Gender(s): Female.
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
Locations and Contacts
Tammy Perkins, RN, Phone: 205-934-4112
University of Alabama at Birmingham, Birmingham, Alabama 35294, United States; Recruiting Kentress Davison, Phone: 205-934-4112 Tammy Perkins, RN, Phone: 205-934-4112
Additional Information
Starting date: July 2010
Last updated: May 26, 2015
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