Bone MetabolismPhase 4NCT00708175
Efficacy of Pioglitazone on Bone Metabolism in Postmenopausal Women With Impaired Fasting Glucose.
A Phase 4 study testing Pioglitazone in people with Bone Metabolism, run by Takeda at 34 sites in United States.
Trial summary
The purpose of this study is to evaluate the effect of pioglitazone on bone metabolism in postmenopausal women with impaired fasting glucose. Read more about this study
- Who is it for?
- Ages Up to 70 years, women only
- Conditions the study is for
- Bone Metabolism
- What is being tested?
- Pioglitazone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 156 participants
- Where
- 34 sitesUnited States
- Study dates
- May 2008to Feb 2011
- 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 Up to 70 years
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Is female and has not experienced menses for at least 5 years.
- Has a Fasting Plasma Glucose level greater than or equal to 100 and less than 126 mg/dL or a 2-hour post-oral glucose tolerance test greater than or equal to 140 and less than or equal to 199 mg/dL at Screening.
- Has a body mass index greater than or equal to 16 and less than or equal to 40 kg/m2 and weighs less than 300 pounds (approximately 136 kilograms).
- Agrees to take daily supplements of Vitamin D (a minimum of 800 IU daily) and calcium (a minimum of 1000 mg daily) during the treatment and wash-out periods.
- Has clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis [fasted for at least 8 hours]) within the reference range for the testing laboratory unless the results are deemed not clinically significant by the investigator or sponsor.
- Is in good health as determined by the physician (ie, via medical history and physical examination) at Screening.
Who cannot join
- Has a fasting triglyceride level greater than 500 mg/dL.
- Has a hemoglobinopathy causing anemia or interfering with glycosylated hemoglobin assays.
- Has an alanine transaminase level greater than or equal to 2.5 times the upper limit of normal, active liver disease or jaundice.
- Has Vitamin D (25-OH-D) less than 20 ng/mL.
- Has Baseline Bone Mineral Density defined as a T-score less than -2.0 at the total hip, spine, or femoral neck based on Caucasian reference values.
- Has unexplained microscopic or macroscopic hematuria confirmed by repeat testing.
Show all 20Show fewer
- Has any of the following disorders:
- Rheumatoid Arthritis
- Thyroid (uncontrolled on thyroid replacement therapy), parathyroid, pituitary, nutritional, inflammatory, gastrointestinal, autoimmune, or renal or other disease known to affect bone metabolism.
- A personal history of kidney stones.
- Has a clinical history after age 45 of wrist, hip, or leg fractures.
- Has a history of more than 1 asymptomatic vertebral deformity or any vertebral deformity attributed to osteoporosis.
- Has a known history of drug abuse (defined as illicit drug use) or a known history of alcohol abuse within 2 years of Screening.
- Has signs and/or symptoms of heart failure.
- Is currently participating in another investigational study or has participated in an investigational study within the past 30 days or 5 half lives of the investigational product, whichever is longer.
- Has any other serious disease or condition at screening or at randomization that might make it difficult to successfully manage and follow up with the subject according to the protocol.
- Has a history of cancer, other than basal cell carcinoma or Stage 1 squamous cell carcinoma of the skin that has not been in remission for at least 5 years prior to the first dose of study drug.
- Has a history of breast cancer.
- Is taking or has ever taken pioglitazone or other Thiazolidinediones.
- Has received or donated blood or blood products within 30 days preceding the Screening visit or plans to donate blood during the study.
Trial locations and contacts
34 sites in 1 country.
34 sites in 1 country
United States34 sites
Study site
Aiken, South Carolina
Study site
Albuquerque, New Mexico
Study site
Bethesda, Maryland
Study site
Boynton Beach, Florida
Study site
Brentwood, Tennessee
Study site
Chicago, Illinois
Study site
Cincinnati, Ohio
Study site
Denton, Texas
Study site
Des Moines, Iowa
Study site
Detroit, Michigan
Study site
Dunwoody, Georgia
Study site
Gainesville, Georgia
Study site
Greenbrae, California
Study site
Greenville, South Carolina
Study site
Hialeah, Florida
Study site
Honolulu, Hawaii
Study site
Houston, Texas
Study site
Idaho Falls, Idaho
Study site
Iowa City, Iowa
Study site
Jupiter, Florida
Study site
Lakewood, Colorado
Study site
Longmont, Colorado
Study site
Los Banos, California
Study site
Louisville, Kentucky
Study site
Metarie, Louisiana
Study site
Mineola, New York
Study site
Omaha, Nebraska
Study site
Pinehurst, North Carolina
Study site
Portland, Oregon
Study site
San Diego, California
Study site
Scarborough, Maine
Study site
Walnut Creek, California
Study site
West Haverstraw, New York
Study site
West Hills, California
About this study
Official title: A Phase 4, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Pioglitazone Compared to Placebo on Bone Metabolism in Impaired Fasting Glucose, Postmenopausal Women for One Year of Treatment
The purpose of this study is to evaluate the effect of pioglitazone on bone metabolism in postmenopausal women with impaired fasting glucose.
Read the detailed description
The World Health Organization has estimated that 30% of all women aged over 50 years (postmenopausal) have osteoporosis according to a definition of Bone Mineral Density at any site being more than 2.5 standard deviations below the mean for young healthy adult women.
A known risk factor for development of osteoporosis and fracture is diabetes mellitus, with correlations to duration of disease and poor glycemic control.
Pioglitazone is a thiazolidinedione developed by Takeda Pharmaceuticals for the treatment of type 2 diabetes. Preclinical studies to date on the bone effects of thiazolidinediones have not clearly identified a mechanism of bone loss. While there is evidence of increased bone fractures in postmenopausal diabetic females treated with a thiazolidinedione, the mechanism is not known. Initial studies with thiazolidinediones in humans have focused on short term exposure (12 to 14 weeks) and non-diabetic females. These studies have shown acute changes in circulating bone markers and bone density, but have been questioned because they may not represent bone metabolism in states of abnormal glucose metabolism. Impaired glucose tolerance has been identified not only as a risk factor for developing type 2 diabetes, but also at higher risk for known complications of diabetes. Examination of the effect of thiazolidinediones on bone metabolism in IGT patients will provide data in patients with abnormal glucose tolerance, but without the potential confounding effects of oral hypoglycemic medications to treat type 2 diabetes.
The primary objective of this study is to evaluate the effect of pioglitazone on bone mass and metabolism in postmenopausal women with impaired fasting glucose or impaired glucose tolerance. Total participation time in this study is approximately 1 year and six months.
- Conditions
- Bone Metabolism
- Being tested
- Pioglitazone, Placebo
- Keywords
- Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Postmenopausal
- Medical subject headings
- Glucose Metabolism Disorders, Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called ACTOS®
Pioglitazone 30 mg, tablets, orally, once daily for 4 weeks, then increased to Pioglitazone 45 mg, tablets, orally, once daily for up to 48 weeks.
PlaceboDrug
Also called ACTOS®
Pioglitazone placebo-matching tablets, orally, once daily for up to 52 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone | Experimental | Not described Receives: Drug: Pioglitazone |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline to Month 12 in Bone Mineral Density in the Total Proximal Femur by Dual-Energy-Ray Absorptiometry (DXA)
The change in bone mineral density in the total proximal femur at month 12 relative to baseline. DXA is a means of measuring BMD through x-ray.
Measured: Baseline and Month 12.
Secondary outcomes (1)
Percent Change From Month 12 to Month 18 in Bone Mineral Density in the Total Proximal Femur by DXA
The change in bone mineral density in the total proximal femur at month 18 relative to month 12. DXA is a means of measuring BMD through x-ray.
Measured: Month 12 and Month 18.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2008 (estimated)
- Study startMay 2008
- Primary completionJan 2011
- Study completionFeb 2011
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bone MetabolismStudies of the same condition, open and under way.
- More trials run by TakedaThe 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- VP Clinical Science Strategy, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00708175
- Sponsor's protocol ID
- AD-4833_402
- Other IDs
- U1111-1115-0660
- Status last verified
- Jan 2012
- First submitted
- 27 Jun 2008
- Last updated
- 3 Feb 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ipsen EO, Madsen KS, Chi Y, Pedersen-Bjergaard U, Richter B, Metzendorf MI, Hemmingsen B. Pioglitazone for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 19;11(11):CD013516. doi: 10.1002/14651858.CD013516.pub2.
PubMed 33210751Bone HG, Lindsay R, McClung MR, Perez AT, Raanan MG, Spanheimer RG. Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2013 Dec;98(12):4691-701. doi: 10.1210/jc.2012-4096. Epub 2013 Sep 20.
PubMed 24057294
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Pioglitazone Compared to Placebo on Bone Metabolism in Impaired Fasting Glucose, Postmenopausal Women for One Year of Treatment
- ClinicalTrials.gov ID
- NCT00708175
- Acronym / sponsor ID
- AD-4833_402
- Conditions
- Bone Metabolism
- Keywords
- Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Postmenopausal
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- May 2008
- Primary completion
- Jan 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 2 Jul 2008 (estimated)
- Results
- Posted 3 Feb 2012
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 evaluate the effect of pioglitazone on bone metabolism in postmenopausal women with impaired fasting glucose.
Detailed description
The World Health Organization has estimated that 30% of all women aged over 50 years (postmenopausal) have osteoporosis according to a definition of Bone Mineral Density at any site being more than 2.5 standard deviations below the mean for young healthy adult women.
A known risk factor for development of osteoporosis and fracture is diabetes mellitus, with correlations to duration of disease and poor glycemic control.
Pioglitazone is a thiazolidinedione developed by Takeda Pharmaceuticals for the treatment of type 2 diabetes. Preclinical studies to date on the bone effects of thiazolidinediones have not clearly identified a mechanism of bone loss. While there is evidence of increased bone fractures in postmenopausal diabetic females treated with a thiazolidinedione, the mechanism is not known. Initial studies with thiazolidinediones in humans have focused on short term exposure (12 to 14 weeks) and non-diabetic females. These studies have shown acute changes in circulating bone markers and bone density, but have been questioned because they may not represent bone metabolism in states of abnormal glucose metabolism. Impaired glucose tolerance has been identified not only as a risk factor for developing type 2 diabetes, but also at higher risk for known complications of diabetes. Examination of the effect of thiazolidinediones on bone metabolism in IGT patients will provide data in patients with abnormal glucose tolerance, but without the potential confounding effects of oral hypoglycemic medications to treat type 2 diabetes.
The primary objective of this study is to evaluate the effect of pioglitazone on bone mass and metabolism in postmenopausal women with impaired fasting glucose or impaired glucose tolerance. Total participation time in this study is approximately 1 year and six months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | Experimental | Drug: Pioglitazone |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- Up to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Is female and has not experienced menses for at least 5 years.
- Has a Fasting Plasma Glucose level greater than or equal to 100 and less than 126 mg/dL or a 2-hour post-oral glucose tolerance test greater than or equal to 140 and less than or equal to 199 mg/dL at Screening.
- Has a body mass index greater than or equal to 16 and less than or equal to 40 kg/m2 and weighs less than 300 pounds (approximately 136 kilograms).
- Agrees to take daily supplements of Vitamin D (a minimum of 800 IU daily) and calcium (a minimum of 1000 mg daily) during the treatment and wash-out periods.
- Has clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis [fasted for at least 8 hours]) within the reference range for the testing laboratory unless the results are deemed not clinically significant by the investigator or sponsor.
Key exclusion criteria (20 listed)
- Has a fasting triglyceride level greater than 500 mg/dL.
- Has a hemoglobinopathy causing anemia or interfering with glycosylated hemoglobin assays.
- Has an alanine transaminase level greater than or equal to 2.5 times the upper limit of normal, active liver disease or jaundice.
- Has Vitamin D (25-OH-D) less than 20 ng/mL.
- Has Baseline Bone Mineral Density defined as a T-score less than -2.0 at the total hip, spine, or femoral neck based on Caucasian reference values.
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 |
|---|---|---|
| PioglitazoneAlso: ACTOS®Pioglitazone 30 mg, tablets, orally, once daily for 4 weeks, then increased to Pioglitazone 45 mg, tablets, orally, once daily for up to 48 weeks. | Drug | Pioglitazone |
| PlaceboAlso: ACTOS®Pioglitazone placebo-matching tablets, orally, once daily for up to 52 weeks. | Drug | Placebo |
Primary outcome
Percent Change From Baseline to Month 12 in Bone Mineral Density in the Total Proximal Femur by Dual-Energy-Ray Absorptiometry (DXA)
Time frame: Baseline and Month 12.
The change in bone mineral density in the total proximal femur at month 12 relative to baseline. DXA is a means of measuring BMD through x-ray.
1 secondary outcome
Percent Change From Month 12 to Month 18 in Bone Mineral Density in the Total Proximal Femur by DXA
Time frame: Month 12 and Month 18.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33210751Ipsen EO, Madsen KS, Chi Y, Pedersen-Bjergaard U, Richter B, Metzendorf MI, Hemmingsen B. Pioglitazone for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 19;11(11):CD013516. doi: 10.1002/14651858.CD013516.pub2.
- Derived from this study: PubMed 24057294Bone HG, Lindsay R, McClung MR, Perez AT, Raanan MG, Spanheimer RG. Effects of pioglitazone on bone in postmenopausal women with impaired fasting glucose or impaired glucose tolerance: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2013 Dec;98(12):4691-701. doi: 10.1210/jc.2012-4096. Epub 2013 Sep 20.
- ACTOS® Package InsertLink provided by the sponsor.
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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.
VP Clinical Science Strategy study director
Takeda
34 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pioglitazone in people with Bone Metabolism, run by Takeda at 34 sites 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 6 inclusion and 20 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: finished, as of the sponsor's last update on 3 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites 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 3 Feb 2012). 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?
Percent Change From Baseline to Month 12 in Bone Mineral Density in the Total Proximal Femur by Dual-Energy-Ray Absorptiometry (DXA) (time frame: Baseline and Month 12.). 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 NCT00708175, which also lists 2 linked publications.
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 3 Feb 2012.