A Phase 4 interventional study of exenatide and Saline in Type 2 Diabetes Mellitus and Bone Remodeling, sponsored by University of Alabama at Birmingham. Terminated at 1 site in United States. Open to female participants aged 45 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-06-14.
Sponsored by University of Alabama at Birmingham · Phase 4, Interventional, and Treatment
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.
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.
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This study's enrollment of 14 is below the median of 80 across 7,525 interventional studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →University of Alabama at Birmingham is the lead sponsor of 1,396 studies on the registry; 284 are open to participants now.
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Study participants in phase1 will receive the study drug, exenatide, at a dose of 5mg subcutaneously twice daily 30 minutes before meals for one month. During the second month of the study, the dose of exenatide will be increased to 10mg subcutaneously twice daily before meals for one month. During the third month of the study, no study medication will be given and this will serve as a "wash out" period prior to the second phase of the study (placebo). During the fourth and fifth months, study participants will get placebo alternatives to exenatide 5mg and exenatide 10mg, respectively, subcutaneously twice daily before meals.
Drug: exenatide · Drug: Saline
Study participants in phase1 will receive the saline placebo, at a dose of 5mcg subcutaneously twice daily 30 minutes before meals for one month. During the second month of the study, the saline placebo will be increased to 10mcg subcutaneously twice daily before meals for one month. During the third month of the study, no treatment will be given and this will serve as a "wash out" period prior to the second phase of the study. During the fourth month study participants will receive Exenatide 5mcg twice daily with meals. During the fifth month, study participants will receive exenatide 10mcg, subcutaneously twice daily before meals.
Drug: exenatide · Drug: Saline
exenatide 5mcg sq twice daily for one month and exenatide 10mcg twice daily for month 2. The 3rd month is a washout period. Month 4 and 5 saline placebo is given as 5mcg and 10mcg respectively.
Also known as: Byetta
Month 1 and 2 saline placebo is given as a low and high dose respectively. The 3rd month is a washout period. Month 4 exenatide 5mcg sq twice daily and for month 5 exenatide 10mcg twice daily is administered.
Also known as: Normal Saline
Determine Changes in Bone Resorption Markers During the Treatment With a GLP-1 Receptor Agonist (Exenatide) Compared to Placebo in Patients With T2DM.
Bone reabsorption by bone-specific alkaline phosphatase (BAP) was assessed. Distribution of the Difference between EX/PBO Low/High Dose and Baseline Levels were calculated.
Time frame: Baseline to 20 weeks
Determine Changes in Bone Turnover Markers by Serum N-Telo Peptide During the Treatment With a GLP-1 Receptor Agonist (Exenatide) Compared to Placebo in Patients With T2DM.
Bone turnover by Serum N-Telo peptide (NTX) was assessed. Distribution of the Difference between EX/PBO Low/High Dose and Baseline Levels were calculated
Time frame: Baseline to 20 weeks
Determine Changes in Bone Turnover Markers by Tartrate-Resistant Acid Phosphatase 5b (TRACP5b) During the Treatment With a GLP-1 Receptor Agonist (Exenatide) Compared to Placebo in Patients With T2DM.
Bone turnover by Tartrate-Resistant Acid Phosphatase 5b (TRACP5b) was assessed. Distribution of the Difference between EX/PBO Low/High Dose and Baseline Levels were calculated.
Time frame: Baseline to 20 weeks
Protocol open to accrual: February 2011, primary completion date, August 2015 and study completion date August 2015. Recruitment location at UAB. Postmenopausal women with diabetes mellitus on no medications or metformin alone were recruited from a single outpatient clinic setting.
| Milestone | Exenatide 1st Then Placebo | Placebo 1st Then Exenatide |
|---|---|---|
| Started | 5 | 5 |
| Completed | 3 | 4 |
| Not completed | 2 | 1 |
| Withdrew: Adverse event | 2 | 0 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Milestone | Exenatide 1st Then Placebo | Placebo 1st Then Exenatide |
|---|---|---|
| Started | 3 | 4 |
| Completed | 3 | 4 |
| Not completed | 0 | 0 |
Bone reabsorption by bone-specific alkaline phosphatase (BAP) was assessed. Distribution of the Difference between EX/PBO Low/High Dose and Baseline Levels were calculated.
| mg/L | Exenatide 1st Then Placebo | Placebo 1st Then Exenatide |
|---|---|---|
| Determine Changes in Bone Resorption Markers During the Treatment With a GLP-1 Receptor Agonist (Exenatide) Compared to Placebo in Patients With T2DM. | 1.925 ± 1.6 | -0.20 ± 3.34 |
Bone turnover by Serum N-Telo peptide (NTX) was assessed. Distribution of the Difference between EX/PBO Low/High Dose and Baseline Levels were calculated
| nMBCE/L | Exenatide Then Placebo | Placebo Then Exenatide |
|---|---|---|
| Determine Changes in Bone Turnover Markers by Serum N-Telo Peptide During the Treatment With a GLP-1 Receptor Agonist (Exenatide) Compared to Placebo in Patients With T2DM. | -0.8 ± 2.31 | 1.725 ± 2.72 |
Bone turnover by Tartrate-Resistant Acid Phosphatase 5b (TRACP5b) was assessed. Distribution of the Difference between EX/PBO Low/High Dose and Baseline Levels were calculated.
| U/L | Exenatide 1st Then Placebo | Placebo 1st Then Exenatide |
|---|---|---|
| Determine Changes in Bone Turnover Markers by Tartrate-Resistant Acid Phosphatase 5b (TRACP5b) During the Treatment With a GLP-1 Receptor Agonist (Exenatide) Compared to Placebo in Patients With T2DM. | 0.05 ± 0.80 | 0.325 ± 0.59 |
Collected over Baseline to 20 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Exenatide 1st Then Placebo | 0/3 (0%) | 0/3 (0%) | 2/3 (66.7%) |
| Placebo 1st Then Exenatide | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) |
| Event | Exenatide 1st Then Placebo | Placebo 1st Then Exenatide |
|---|---|---|
| Nausea/vomiting (1st treatment period)Gastrointestinal disorders | 1/3 | 0/4 |
| Pruritis (2nd treatment period)Skin and subcutaneous tissue disorders | 1/3 | 0/4 |
This is a crossover study. Not all patients completed both arms of the study. 14 patients were screened. 10 presented for the baseline study and were provided some study medication. 1 participant's specimen was not analyzed and she is not included in analysis for that reason. 5 started Exenatide; 5 started Placebo.
| Age, Continuous(years) | Placebo 1st Then Exenatide | Exenatide 1st Then Placebo | Total |
|---|---|---|---|
| Median | 61 ± 4.2 | 61 ± 3.8 | 61 ± 4.0 |
| Sex: Female, Male(Participants) | Placebo 1st Then Exenatide | Exenatide 1st Then Placebo | Total |
|---|---|---|---|
| Female | 5 | 5 | 10 |
| Male | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Placebo 1st Then Exenatide | Exenatide 1st Then Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 2 | 2 | 4 |
| White | 3 | 3 | 6 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Placebo 1st Then Exenatide | Exenatide 1st Then Placebo | Total |
|---|---|---|---|
| United States | 5 | 5 | 10 |
Plan to share: Undecided
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University of Alabama at Birmingham