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unavailability of study drug and matching placebo
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| Name | Class |
|---|---|
| Amylin Pharmaceuticals, LLC. | INDUSTRY |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Exenatide then Placebo | Experimental | 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. |
|
| Placebo then Exenatide | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| exenatide | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 | 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. | Baseline to 20 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amy Warriner, MD | University of Alabama at Birmingham | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States |
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Potential participants attended a screening visit to ensure they met inclusion/exclusion criteria. If they were on metformin at the screening visit, it was discontinued. They returned in 1 month for the baseline visit and randomization.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Exenatide 1st Then Placebo | Study participants in period 1 will receive the study drug, exenatide, at a dose of 5mcg 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 10mcg 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 period of the study (placebo). During the fourth and fifth months, study participants will get placebo alternatives to exenatide 5mcg and exenatide 10mcg, respectively, subcutaneously twice daily before meals. |
| FG001 | Placebo 1st Then Exenatide | Study participants in periods1 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 dose of 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 periods of the study. During the fourth month participants will receive Exenatide 5mcg twice daily before meals. During the fifth month, study participants will get Exenatide 10mcg twice daily before meals. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Low/High Dose of 1st Treatment (2months) |
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| Low/High Dose of 2nd Treatment (2months) |
|
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.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo 1st Then Exenatide | Study participants in period1 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 dose of 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 periods of the study. During the fourth month participants will receive Exenatide 5mcg twice daily before meals. During the fifth month, study participants will get Exenatide 10mcg twice daily before meals. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | For Crossover study, participants were matched for the placebo and study drug arms. As such, only data from participants completing both arms were included in the statistical analysis. | Posted | Mean | Standard Deviation | mg/L | Baseline to 20 weeks |
|
Baseline to 20 weeks
clinicaltrials.gov definitions used
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Exenatide 1st Then Placebo | Study participants in phase1 will receive the study drug, exenatide, at a dose of 5mcg 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 10mcg 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 5mcg and exenatide 10mcg, respectively, subcutaneously twice daily before meals. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea/vomiting (1st treatment period) | Gastrointestinal disorders | Systematic Assessment |
Study was closed due to unavailability of study drug/matching placebo prior to recruitment of target participants. The original drug company was bought and new company was unwilling to supply medication. Small participant number limits data analysis.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Amy Warriner | UAB | 205-996-4004 | awarriner@uabmc.edu |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000077270 | Exenatide |
| D012965 | Sodium Chloride |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014688 | Venoms |
| D045424 | Complex Mixtures |
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|
| Saline | Drug | 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. |
|
|
| NOT COMPLETED |
|
| BG001 | Exenatide 1st Then Placebo | Study participants in period 1 will receive the study drug, exenatide, at a dose of 5mcg 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 10mcg 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 period of the study (placebo). During the fourth and fifth months, study participants will get placebo alternatives to exenatide 5mcg and exenatide 10mcg, respectively, subcutaneously twice daily before meals. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo 1st Then Exenatide | 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 dose of 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 participants will receive Exenatide 5mcg twice daily before meals. During the fifth month, study participants will get Exenatide 10mcg twice daily before meals. |
|
|
| Primary | 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 | For Crossover, study, participants were matched for the placebo and study drug arms. As such, only data from participants completing both arms were included in the statistical analysis. | Posted | Mean | Standard Deviation | nMBCE/L | Baseline to 20 weeks |
|
|
|
| Primary | 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. | For Crossover, study, participants were matched for the placebo and study drug arms. As such, only data from participants completing both arms were included in the statistical analysis. | Posted | Mean | Standard Deviation | U/L | Baseline to 20 weeks |
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 2 |
| 3 |
| EG001 | Placebo 1st Then Exenatide | 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 dose of 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 participants will receive Exenatide 5mcg twice daily before meals. During the fifth month, study participants will get Exenatide 10mcg twice daily before meals. | 0 | 4 | 0 | 4 | 0 | 4 |
| Pruritis (2nd treatment period) | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
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| D004700 | Endocrine System Diseases |
| D014118 |
| Toxins, Biological |
| D001685 | Biological Factors |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |