Type 2 Diabetes MellitusPhase 4DRTCNCT01374568
Changes in Bone Turnover With Increased Incretin Hormone Exposure
A Phase 4 study testing sitagliptin in people with Type 2 Diabetes Mellitus, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
The purpose of this study is to determine if the use of sitagliptin increases bone formation and reduces bone turnover in postmenopausal women with 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
- What is being tested?
- sitagliptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2010to Sep 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 >55 years old or amenorrhea for >1years)
- 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.
- Hemoglobin A1c (HbA1c) of 6.5-9.0%
Who cannot join
- Use of an incretin mimetic (i.e. exenatide), 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
About this study
Official title: Changes in Bone Turnover With Increased Incretin Hormone Exposure (UAB Diabetes Research and Training Center Pilot and Feasibility Study)
The purpose of this study is to determine if the use of sitagliptin increases bone formation and reduces bone turnover in postmenopausal women with type 2 diabetes.
Read the detailed description
Patients with Type 2 Diabetes Mellitus (T2DM) are at an increased risk of fracture, despite having bone mineral density (BMD) 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, incretins have been a therapeutic target for the treatment of T2DM through GLP-1 receptor analogs or inhibition of incretin metabolism via dipeptidyl peptidase 4 (DPP-4) inhibitors (i.e. sitagliptin). Inhibition of DPP-4 leads to an approximate doubling of GLP-1 and GIP levels but also leads to reduced breakdown of GLP-2.
Less is known about the effect of incretin-directed therapies, specifically sitagliptin, and bone metabolism. To our knowledge, two studies have looked at the direct effects of currently available incretin-directed therapies on bone metabolism. Exenatide (a GLP-1 analog) treatment of insulin resistant and type 2 diabetic rats resulted in osteogenic effects with increased osteocalcin levels following treatment. In a study of female non-diabetic Sprague-Dawley rats treated with pioglitazone, rosiglitazone, sitagliptin, vs. placebo, no significant change in bone mineral density was seen in the sitagliptin or placebo treated rats (compared to significant loss of bone mineral density in the TZD groups). Even fewer published studies are available evaluating changes in bone metabolism with the use of incretin hormones in humans. The majority of the human studies have been completed with GLP-2. These studies show a dose-dependent effect of GLP-2 on bone resorption and, preliminarily, show improved bone mineral density in postmenopausal women treated with GLP-2. However, the changes in incretin activity vary in persons with glucose intolerance and T2DM. Therefore, it is important to understand the potential effects of these medications on bone metabolism in persons prescribed these medications for treatment of their T2DM.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- sitagliptin, Placebo
- Keywords
- Type 2 diabetes, sitagliptin, Januvia
- 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.
sitagliptinDrug
Also called Januvia
sitagliptin 100mg daily
PlaceboOther
1 pill daily
| Study group | Role | What they receive |
|---|---|---|
| sitagliptin | Active comparator | Sitagliptin Receives: Drug: sitagliptin |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone Turnover in Subjects Treated With Sitagliptin When Compared to Those Treated With Placebo.
Bone turnover assessed using change in TRACP5b over 8 weeks of treatment.
Measured: 8 weeks
Bone Turnover in Subjects Treated With Sitagliptin When Compared to Those Treated With Placebo
Bone turnover assessed using change in bone-specific alkaline phosphatase (BAP) over 8 weeks of treatment.
Measured: 8 WEEKS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2011 (estimated)
- Study startJul 2010
- Primary completion6 Jul 2012
- Study completionSep 2015
Why it stopped: Study closed by sponsor. Funding ended.
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
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amy H. Warriner, University of Alabama at Birmingham
- Investigators
- Amy Warriner, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01374568
- Sponsor's protocol ID
- UAB F100317002
- Acronym
- DRTC
- Status last verified
- Jun 2017
- First submitted
- 10 Jun 2011
- Last updated
- 24 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Changes in Bone Turnover With Increased Incretin Hormone Exposure (UAB Diabetes Research and Training Center Pilot and Feasibility Study)
- ClinicalTrials.gov ID
- NCT01374568
- Acronym / sponsor ID
- DRTC / UAB F100317002
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Type 2 diabetes, sitagliptin, Januvia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study closed by sponsor. Funding ended.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- Jul 2010
- Primary completion
- 6 Jul 2012 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 16 Jun 2011 (estimated)
- Results
- Posted 31 May 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 if the use of sitagliptin increases bone formation and reduces bone turnover in postmenopausal women with type 2 diabetes.
Detailed description
Patients with Type 2 Diabetes Mellitus (T2DM) are at an increased risk of fracture, despite having bone mineral density (BMD) 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, incretins have been a therapeutic target for the treatment of T2DM through GLP-1 receptor analogs or inhibition of incretin metabolism via dipeptidyl peptidase 4 (DPP-4) inhibitors (i.e. sitagliptin). Inhibition of DPP-4 leads to an approximate doubling of GLP-1 and GIP levels but also leads to reduced breakdown of GLP-2.
Less is known about the effect of incretin-directed therapies, specifically sitagliptin, and bone metabolism. To our knowledge, two studies have looked at the direct effects of currently available incretin-directed therapies on bone metabolism. Exenatide (a GLP-1 analog) treatment of insulin resistant and type 2 diabetic rats resulted in osteogenic effects with increased osteocalcin levels following treatment. In a study of female non-diabetic Sprague-Dawley rats treated with pioglitazone, rosiglitazone, sitagliptin, vs. placebo, no significant change in bone mineral density was seen in the sitagliptin or placebo treated rats (compared to significant loss of bone mineral density in the TZD groups). Even fewer published studies are available evaluating changes in bone metabolism with the use of incretin hormones in humans. The majority of the human studies have been completed with GLP-2. These studies show a dose-dependent effect of GLP-2 on bone resorption and, preliminarily, show improved bone mineral density in postmenopausal women treated with GLP-2. However, the changes in incretin activity vary in persons with glucose intolerance and T2DM. Therefore, it is important to understand the potential effects of these medications on bone metabolism in persons prescribed these medications for treatment of their T2DM.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sitagliptin | Active comparator | Drug: sitagliptinSitagliptin |
| Placebo | Placebo comparator | Other: PlaceboPlacebo |
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 >55 years old or amenorrhea for >1years)
- 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.
- Hemoglobin A1c (HbA1c) of 6.5-9.0%
Key exclusion criteria (4 listed)
- Use of an incretin mimetic (i.e. exenatide), 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 |
|---|---|---|
| sitagliptinAlso: Januviasitagliptin 100mg daily | Drug | sitagliptin |
| Placebo1 pill daily | Other | Placebo |
Primary outcome
Bone Turnover in Subjects Treated With Sitagliptin When Compared to Those Treated With Placebo.
Time frame: 8 weeks
Bone turnover assessed using change in TRACP5b over 8 weeks of treatment.
Bone Turnover in Subjects Treated With Sitagliptin When Compared to Those Treated With Placebo
Time frame: 8 WEEKS
Bone turnover assessed using change in bone-specific alkaline phosphatase (BAP) over 8 weeks of treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 sitagliptin in people with Type 2 Diabetes Mellitus, 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 24 Jul 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. Some participants in this study may receive a placebo. 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 31 May 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?
Bone Turnover in Subjects Treated With Sitagliptin When Compared to Those Treated With Placebo. (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Jul 2017.