Type 2 Diabetes MellitusPhase 4CMBDNCT01381926

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

A Phase 4 study testing exenatide and Saline in people with Type 2 Diabetes Mellitus and Bone Remodeling, run by University of Alabama at Birmingham at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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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. Read more about this study

Who is it for?: Ages 45 years and older, women onlyHealthy volunteers can take part
Conditions the study is for: Type 2 Diabetes Mellitus, Bone Remodeling
What is being tested?: exenatide and Saline
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 1 siteUnited States
Study dates: Feb 2011to Aug 2015
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 45 years and older
Women only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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%

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Alabama at Birmingham
Birmingham, Alabama, 35294

Other trials in United States

About this study

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

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.

Read the 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.

Conditions: Type 2 Diabetes Mellitus, Bone Remodeling
Being tested: exenatide, Saline
Keywords: Type 2 diabetes, exenatide, Byetta
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

exenatideDrug
Also called Byetta
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.
SalineDrug
Also called Normal Saline
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.

Study groups in NCT01381926
Study group	Role	What they receive
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. Receives: Drug: exenatide; Drug: Saline
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. Receives: Drug: exenatide; Drug: Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
Measured: 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.
Measured: Baseline to 20 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2011Aug 2015

First posted27 Jun 2011 (estimated)
Study startFeb 2011
Primary completionAug 2015
Study completionAug 2015

Why it stopped: unavailability of study drug and matching placebo

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01381926
Sponsor's protocol ID: F100929001
Acronym: CMBD
Status last verified: May 2017
First submitted: 13 Jun 2011
Last updated: 14 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Changes in Bone Turnover With Exposure to a GLP-1 Receptor Agonist (UAB Core Center for Basic Skeletal Research)
ClinicalTrials.gov ID: NCT01381926
Acronym / sponsor ID: CMBD / F100929001
Conditions: Type 2 Diabetes Mellitus, Bone Remodeling
Keywords: Type 2 diabetes, exenatide, Byetta
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: unavailability of study drug and matching placebo
Enrolment: 14 participants (actual)
Lead sponsor: University of Alabama at BirminghamUniversity, hospital or other
Collaborators: Amylin Pharmaceuticals, LLC.
Study start: Feb 2011
Primary completion: Aug 2015 (actual)
Study completion: Aug 2015 (actual)
First posted: 27 Jun 2011 (estimated)
Results: Posted 14 Jun 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Exenatide then Placebo	Experimental	Drug: exenatide, Drug: SalineStudy 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	Drug: exenatide, Drug: SalineStudy 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.

Who may qualify

Ages: 45 years and older
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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%

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
exenatideAlso: Byettaexenatide 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.	Drug	Exenatide then Placebo, Placebo then Exenatide
SalineAlso: Normal SalineMonth 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.	Drug	Exenatide then Placebo, Placebo then Exenatide

Primary outcome

Determine Changes in Bone Resorption Markers During the Treatment With a GLP-1 Receptor Agonist (Exenatide) Compared to Placebo in Patients With T2DM.
Time frame: Baseline to 20 weeks
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.
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.
Time frame: Baseline to 20 weeks
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
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.
Time frame: Baseline to 20 weeks
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.

Results and safety

Results posted to the registry on 14 Jun 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Exenatide 1st Then Placebo	5	3
Placebo 1st Then Exenatide	5	4

Primary outcome: Determine Changes in Bone Resorption Markers During the Treatment With a GLP-1 Receptor Agonist (Exenatide) Compared to Placebo in Patients With T2DM.

Time frame: Baseline to 20 weeks. Mean (Standard Deviation). Unit: mg/L

Measure	Exenatide 1st Then Placebo n = 3	Placebo 1st Then Exenatide n = 4
Value	1.925 (1.6)	-0.20 (3.34)

Population analysed: 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.

Primary outcome: 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.

Time frame: Baseline to 20 weeks. Mean (Standard Deviation). Unit: nMBCE/L

Measure	Exenatide Then Placebo n = 3	Placebo Then Exenatide n = 4
Value	-0.8 (2.31)	1.725 (2.72)

Population analysed: 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.

Primary outcome: 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.

Time frame: Baseline to 20 weeks. Mean (Standard Deviation). Unit: U/L

Measure	Exenatide 1st Then Placebo n = 3	Placebo 1st Then Exenatide n = 4
Value	0.05 (0.80)	0.325 (0.59)

Adverse events

Time frame: Baseline to 20 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Exenatide 1st Then Placebo	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Placebo 1st Then Exenatide	0 of 4 (0%)	0 of 4 (0%)	0 of 4

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Undecided

Related trials for Type 2 Diabetes Mellitus

Active, not recruitingPhase 2
A Study on the Safety and Clinical Efficacy of Guominkang in the Treatment of Diabetic Kidney Disease
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Amy Warriner, MD principal investigator

University of Alabama at Birmingham

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing exenatide and Saline in people with Type 2 Diabetes Mellitus and Bone Remodeling, run by University of Alabama at Birmingham at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine Changes in Bone Resorption Markers During the Treatment With a GLP-1 Receptor Agonist (Exenatide) Compared to Placebo in Patients With T2DM. (time frame: Baseline to 20 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01381926.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2017.