Changes in Bone Turnover With Exposure to a GLP-1 Receptor Agonist (CMBD)

This study is currently recruiting participants.
Verified November 2013 by University of Alabama at Birmingham
Sponsor:
Collaborator:
Amylin Pharmaceuticals, LLC.
Information provided by (Responsible Party):
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01381926
First received: June 13, 2011
Last updated: December 4, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to determine changes in bone turnover markers and calcitonin following the initiation of exenatide compared to placebo in postmenopausal women wtih type 2 diabetes.

Hypothesis 1a: Bone resorption (measured by osteocalcin and bone-specific alkaline phosphatase) will be lower and bone formation (measured by type I collagen crosslinked aminoterminal peptide in urine (Urine NTX)) will be higher when subjects are treated with exenatide compared to when subjects are treated with placebo.

Hypothesis 1b: Calcitonin levels will not vary significantly between periods of treatment with exenatide vs. placebo.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: exenatide
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Health Services Research
Official Title: Changes in Bone Turnover With Exposure to a GLP-1 Receptor Agonist (UAB Core Center for Basic Skeletal Research)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Determine changes in bone turnover and bone resorption markers during the treatment with a GLP-1 Receptor Agonist (exenatide) compared to placebo in patients with T2DM. [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    This study will evaluate the effect of a GLP-1 receptor agonist on bone turnover markers and calcitonin in postmenopausal women with Type 2 Diabetes Mellitus. Bone resorption (measured by osteocalcin and bone-specific alkaline phosphatase) will be lower and bone formation (measured by urine NTX) will be higher when subjects are treated with exenatide compared to placebo.


Secondary Outcome Measures:
  • Calcitonin levels will not vary significantly between periods of treatment with exenatide vs. placebo. [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    In rodent models, calcitonin levels rise significantly following treatment with GLP-1 receptor agonists, leading to c-cell hyperplasia. However, review of calcitonin changes in humans and cynomolgus monkeys treated with GLP-1 receptor agonists have not shown similar results. This study will test the hypothesis that calcitonin levels will not vary significantly between periods of treatment with exenatide vs. placebo by measuring calcitonin levels.


Estimated Enrollment: 30
Study Start Date: February 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Saline
placebo
Drug: placebo
placebo twice daily
Other Name: Saline injection
Active Comparator: exenatide
exenatide
Drug: exenatide
exenatide 5mcg sq twice daily and exenatide 10mcg twice daily
Other Name: Byetta

Detailed Description:

Patients with Type 2 Diabetes Mellitus (T2DM) are at an increased risk of fracture, despite having bone mineral density (BMD) levels 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, incretin hormones have been a therapeutic target for the treatment of T2DM through GLP-1 receptor agonists (i.e. exenatide) or inhibition of incretin hormone metabolism via dipeptidyl peptidase 4 (DPP-4)inhibitors. The GLP-1 receptor analog exenatide leads to an approximate 13-fold increased GLP-1 effect compared to approximate doubling of incretin hormone levels with current DDP-4 inhibitors. In rodent models, calcitonin levels rise significantly following treatment with GLP-1 receptor agonists, leading to c-cell hyperplasia. However, review of calcitonin changes in humans and cynomolgus monkeys treated with GLP-1 receptor agonists have not shown similar results.

  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 ≥45 years old or amenorrhea for >2years)
  • 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. If on a medication for diabetes prior to study entry, the medication can be discontinued for 2 weeks prior to study initiation.
  • Hemoglobin A1c (HbA1c) of 6.5-9.0%

Exclusion Criteria:

  • Use of an incretin mimetic (i.e. exenatide, liraglutide), 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01381926

Contacts
Contact: Tiffany Grimes, RN 205-934-4112
Contact: Marianne Vetrano, RN 205-934-4112

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Susan Ferguson, LPN    205-934-4112      
Contact: Kentress Davison    205-934-4112      
Principal Investigator: Amy Warriner, MD         
Sponsors and Collaborators
University of Alabama at Birmingham
Amylin Pharmaceuticals, LLC.
Investigators
Principal Investigator: Amy Warriner, MD University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01381926     History of Changes
Other Study ID Numbers: F100929001
Study First Received: June 13, 2011
Last Updated: December 4, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of Alabama at Birmingham:
Type 2 diabetes, exenatide, Byetta

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014