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

Type 2 Diabetes Mellitus Clinical Trial

— CMBD  

Official title:

Changes in Bone Turnover With Exposure to a GLP-1 Receptor Agonist (UAB Core Center for Basic Skeletal Research)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01381926
• Other study ID #: F100929001
• Status: Completed
• Phase: Phase 4
• First received: June 13, 2011
• Last updated: December 23, 2016
• Start date: February 2011
• Est. completion date: August 2015

Study information

• Verified date: December 2016
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Health Services Research

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• exenatide
exenatide 5mcg sq twice daily and exenatide 10mcg twice daily
• placebo
placebo twice daily

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Amylin Pharmaceuticals, LLC.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	14 weeks	No
Secondary	Calcitonin levels will not vary significantly between periods of treatment with exenatide vs. placebo.	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.	14 weeks	No