Effect of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes (Pioglitazone)

June 16, 2014 updated by: Mohammed-Salleh M. Ardawi, King Abdulaziz University

Phase 1 Study of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes

The study tests whether pioglitazone (PIO)as compared to metformin (MET)affects bone health including bone mineral density, bone turnover markers, and osteocyte biomarker in patients with type 2 diabetes (T2DM).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Women with T2DM exhibit normal or higher bone mineral density (BMD) for their age, but with approximately twice the overall risk of bone fragility compared with nondiabetic subjects. Known the apparent association between T2DM and the risk of bone fragility, examining the effects of commonly used oral antidiabetic agents; such as MET and thiazolidinediones (TZDs; for example rosiglitazone [ROS] or PIO), on BMD and/or bone turnover is of great clinical relevance for both diabetic patients and their treating physicians. Recent clinical trials, showed that women treated with ROS had higher risk of bone fragility and self-reported adverse events. Similarly, women on long-term treatment with PIO for T2DM experienced higher incidence of distal extremity fractures. TZDs are agonists of the nuclear transcription factor peroxisome proliferator- activated receptor-γ (PPAR-γ) which increase insulin sensitivity and improve glycemic control in T2DM. PPAR (γ) acts also as a molecular factor that favours adipogenesis over osteoblastogenesis of mesenchymal stem cells. The latter was suggested as a potential mechanism for the effects of TZDs on bone among others. In humans, TZDs decrease BMD and increase bone fragility risk. This study tests whether pioglitazone as compared to MET (both are commonly used in the treatment of T2DM in Saudi Arabia and other countries) affects bone health including bone mineral density, bone turnover markers, and osteocyte biomarker in patients with T2DM.

Study Type

Interventional

Enrollment (Anticipated)

440

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Saudi Arabia
    • Makkah
      • Jeddah, Makkah, Saudi Arabia, 21589
        • Center of Excellence for Osteoporosis Research, King Abdulaziz University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • BMD T-score greater than -2.5 at the total hip, femoral neck, and lumbar spine;
  • No prior antidiabetic therapy;
  • Drug-naïve with glycosylated hemoglobin A1c (HbA1c) ≥ 7.0 to ≤ 10.0%. 53.2 mmol/mol to 88.2 mmol/mol);
  • Body-mass index of 40 Kg/m2 and less;
  • Stable body weight for at least 4 months.

Exclusion Criteria:

  • Type 1 diabetes mellitus (presence of GAD auto antibodies);
  • History of diabetes or uncontrolled hypertension;
  • Treatment with antidiabetic agents including TZDs;
  • Chronic diseases known to affect bone;
  • Previous treatment with estrogens and other medications known to affect bone ;
  • Creatinine clearance less than 60 ml/min

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental: 1
Pioglitazone given 30mg/once daily for 12 months.
Drug: Pioglitazone
30 mg/daily for 12 months
Other Names:
  • Actos
Active Comparator: Active comparator: 2
Metformin given 850 mg/twice daily for 12 months.
Drug: Metformin
850 mg/daily for 12 months
Other Names:
  • Glucophage

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in mean percentage change in BMD at various sites by Dual energy X-ray absorptiometry(DXA) from baseline and at 6, 12 months in PIO versus MET treatment group.
Time Frame: 6-18 months
The primary endpoint was change in mean percentage change in BMD values at the lumbar spine (L1-L4), femoral neck and total hip by DXA from baseline and at 6 and 12 months in the PIO and the MET treatment groups.
6-18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone turnover Markers and other Biomarkers
Time Frame: 6-18 months
Secondary end-points were changes in serum sclerostin, serum bone-specific alkaline phosphatase (BSAP), serum procollagen type1 N-terminal propeptide (P1NP) and serum C-terminal crosslinking telopeptide of type 1 collagen (CTX); and urinary N-terminal crosslinking telopeptide type 1 collagen (u-NTX); serum calcium, 25-hydroxyvitamin D (25-OHD), and serum Dickkopf-1( DKK-1) at various time intervals from baseline between PIO vs MET treatment.
6-18 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exploratory and Safety Outcomes
Time Frame: 6-18 months
Other endpoints were changes in inflammatory markers (hs-CRP)
6-18 months
Exploratory Outcomes: lipid profile
Time Frame: 6-18 months
lipid profile (total cholesterol, HDL-c, LDL-c and triglycerides)
6-18 months
Exploratory outcomes: liver and renal function tests
Time Frame: 6-18 months
liver function tests [albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)]; renal function tests (creatinine, urea, uric acid) and parathyroid hormone (PTH).
6-18 months
Exploratory outcomes: glycemic control
Time Frame: 6-18 months
within and between treatment group comparisons of change from baseline at specified time points in HbA1c, fasting plasma glucose (FPG), fasting plasma insulin, and insulin sensitivity measured by the homeostasis model assessment (HOMA-s).
6-18 months
Exploratory and safety outcomes
Time Frame: 6-18 months
Safety endpoints were adverse events (AEs), clinical laboratory assessments, vital signs, and electrocardiograms
6-18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

King Abdulaziz University

Investigators

  • Principal Investigator: Mohammed-Salleh M Ardawi, PhD, FRCPath, Center of Excellence for Osteoporosis Research and Faculty of Medicine, King Abdulaziz University
  • Study Director: Abdulrahim A Rouzi, FRCPC, Center of Excellence for Osteoporosis Research, and Faculty of Medicine, King Abdulaziz University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Actual)

January 1, 2014

Study Completion (Actual)

January 1, 2014

Study Registration Dates

First Submitted

August 27, 2013

First Submitted That Met QC Criteria

September 2, 2013

First Posted (Estimate)

September 5, 2013

Study Record Updates

Last Update Posted (Estimate)

June 17, 2014

Last Update Submitted That Met QC Criteria

June 16, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CEOR-01-08

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Glucose Metabolism Disorders

Clinical Trials on Pioglitazone

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Italy

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe