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

Primary Purpose

Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders

Status
Completed
Phase
Phase 2
Locations
Saudi Arabia
Study Type
Interventional
Intervention
Pioglitazone
Metformin
Sponsored by
King Abdulaziz University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus focused on measuring pioglitazone, metformin, hyperglycemic agents, physiological effects of drugs, bone health

Eligibility Criteria

50 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Center of Excellence for Osteoporosis Research, King Abdulaziz University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental: 1

Active comparator: 2

Arm Description

Pioglitazone given 30mg/once daily for 12 months.

Metformin given 850 mg/twice daily for 12 months.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Bone turnover Markers and other Biomarkers
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.

Full Information

First Posted
August 27, 2013
Last Updated
June 16, 2014
Sponsor
King Abdulaziz University
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1. Study Identification

Unique Protocol Identification Number
NCT01935804
Brief Title
Effect of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes
Acronym
Pioglitazone
Official Title
Phase 1 Study of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
King Abdulaziz University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders
Keywords
pioglitazone, metformin, hyperglycemic agents, physiological effects of drugs, bone health

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
440 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: 1
Arm Type
Experimental
Arm Description
Pioglitazone given 30mg/once daily for 12 months.
Arm Title
Active comparator: 2
Arm Type
Active Comparator
Arm Description
Metformin given 850 mg/twice daily for 12 months.
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Other Intervention Name(s)
Actos
Intervention Description
30 mg/daily for 12 months
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage
Intervention Description
850 mg/daily for 12 months
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
6-18 months
Secondary Outcome Measure Information:
Title
Bone turnover Markers and other Biomarkers
Description
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.
Time Frame
6-18 months
Other Pre-specified Outcome Measures:
Title
Exploratory and Safety Outcomes
Description
Other endpoints were changes in inflammatory markers (hs-CRP)
Time Frame
6-18 months
Title
Exploratory Outcomes: lipid profile
Description
lipid profile (total cholesterol, HDL-c, LDL-c and triglycerides)
Time Frame
6-18 months
Title
Exploratory outcomes: liver and renal function tests
Description
liver function tests [albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)]; renal function tests (creatinine, urea, uric acid) and parathyroid hormone (PTH).
Time Frame
6-18 months
Title
Exploratory outcomes: glycemic control
Description
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).
Time Frame
6-18 months
Title
Exploratory and safety outcomes
Description
Safety endpoints were adverse events (AEs), clinical laboratory assessments, vital signs, and electrocardiograms
Time Frame
6-18 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mohammed-Salleh M Ardawi, PhD, FRCPath
Organizational Affiliation
Center of Excellence for Osteoporosis Research and Faculty of Medicine, King Abdulaziz University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Abdulrahim A Rouzi, FRCPC
Organizational Affiliation
Center of Excellence for Osteoporosis Research, and Faculty of Medicine, King Abdulaziz University
Official's Role
Study Director
Facility Information:
Facility Name
Center of Excellence for Osteoporosis Research, King Abdulaziz University
City
Jeddah
State/Province
Makkah
ZIP/Postal Code
21589
Country
Saudi Arabia

12. IPD Sharing Statement

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

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