Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000610437
Ethics application status
Approved
Date submitted
26/11/2007
Date registered
28/11/2007
Date last updated
5/12/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
The bone effects of pioglitazone
Scientific title
A randomized controlled trial of the effects of pioglitazone on bone density and bone turnover in type 2 diabetes mellitus
Secondary ID [1] 259739 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes mellitus 2582 0
Osteoporosis 2583 0
Condition category
Condition code
Metabolic and Endocrine 2692 2692 0 0
Diabetes
Musculoskeletal 2693 2693 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pioglitazone 30mg per oral daily for 12 months
Intervention code [1] 2316 0
Treatment: Drugs
Comparator / control treatment
Placebo, sugar pill, per oral
Control group
Placebo

Outcomes
Primary outcome [1] 3593 0
Change in lumbar spine bone density, measured by dual energy xray absorptiometry
Timepoint [1] 3593 0
1 year after randomization
Secondary outcome [1] 6016 0
Change in total hip bone density, measured by dual energy xray absorptiometry
Timepoint [1] 6016 0
1 year after randomization
Secondary outcome [2] 6017 0
Chnage in biochemical markers of bone formation, assayed in serum
Timepoint [2] 6017 0
1 year after randomization

Eligibility
Key inclusion criteria
- Type 2 diabetes mellitus (T2DM), as defined by fasting blood glucose > 7mmol/L and/or serum glucose > 11mmol/L 2h after ingesting 75g oral glucose.
- impaired glucose tolerance, as defined by fasting blood glucose < 6-7 mmol/L and/or serum glucose 7.8-11mmol/L 2h after ingesting 75g oral glucose
Minimum age
30 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Medical Conditions
- subjects with type 2 diabetes mellitus (T2DM) deemed to require early glitazone treatment and meeting Pharmac criteria for funded supply
- renal impairment (estimated glomerular filtration rate < 30ml/min).
- congestive heart failure, New York Heart Association Grade 2 or higher
- clinical liver disease.
- untreated thyroid dysfunction.
- concurrent major systemic illness, including malignancy.
- metabolic bone diseases, or serum alkaline phosphatase (ALP) > 2x normal limit.
- primary hyperparathyroidism.
- Bone mineral density (BMD) T score < -2.0 at total hip or spine
- previous fragility fracture (forearm, humerus, hip, vertebra)
- body weight >120kg

2.2.2 Medications
- use of oral glucocorticoid drugs equivalent to an average dose of prednisone = 2.5 mg/day in the preceding 12 months
- current or past use of bisphosphonate therapy
- use of hormone replacement therapy within the last 12 months
- use of other medication known to alter bone metabolism
- current use of thiazolidinediones

Insulin use is not an exclusion criterion, but insulin dose should be stable (+/- 20%) for 3 months before enrolment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is concealed. Allocation involves contacting the holder of the allocation schedule who is "off-site"
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization will be undertaken using a variable block size schedule, based on computer-generated random numbers, stratified for age, menopausal status, and gender.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
This is a 1 year randomized interventional protocol, with a 1 year observational follow-up period
Phase
Phase 4
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2008
Actual
1/10/2008
Date of last participant enrolment
Anticipated
30/04/2011
Actual
30/04/2011
Date of last data collection
Anticipated
Actual
30/04/2012
Sample size
Target
100
Accrual to date
Final
86
Recruitment outside Australia
Country [1] 697 0
New Zealand
State/province [1] 697 0

Funding & Sponsors
Funding source category [1] 2834 0
Government body
Name [1] 2834 0
Health Research Council of New Zealand
Country [1] 2834 0
New Zealand
Primary sponsor type
Individual
Name
Andrew Grey
Address
Department of Medicine
University of Auckland
Private bag 92019
Auckland
Country
New Zealand
Secondary sponsor category [1] 2553 0
University
Name [1] 2553 0
University of Auckland
Address [1] 2553 0
Private Bag 92019
Auckland
Country [1] 2553 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4762 0
Northern Y Regional Ethics Committee
Ethics committee address [1] 4762 0
Ministry of Health
2rd Floor, BNZ Building
354 Victoria St
PO Box 1031
Hamilton
New Zealand
Ethics committee country [1] 4762 0
New Zealand
Date submitted for ethics approval [1] 4762 0
20/11/2007
Approval date [1] 4762 0
04/04/2008
Ethics approval number [1] 4762 0
NTY/07/12/128

Summary
Brief summary
Type 2 diabetes mellitus (T2DM) is a common disease that is associated with an increased risk of bone fracture. Recent evidence suggests that pioglitazone, a drug commonly used to treat T2DM by improving the effectiveness of action of the hormone insulin, may increase the risk of bone fracture, by decreasing the activity of bone-forming cells and thereby bone density. At present, little is known about the actions of pioglitazone on bone in humans. Our study is designed to determine the mechanism, magnitude and reversibility of the effects of pioglitazone on blood markers of bone metabolism and bone density in subjects with T2DM. Some evidence suggests that pioglitazone may increase the risk of heart failure, although it may also decrease the risk of heart attack and stroke. We intend to perform blood and ultrasound measurements of heart function in the subjects who participate in our study.
The results of the study will assist T2DM patients and their doctors in decisions around use of pioglitazone, the need for bone and/or heart monitoring in patients taking pioglitazone, and use of treatments to prevent bone loss in patients taking pioglitazone.
Trial website
Trial related presentations / publications
Grey A, Bolland M, Fenwick S, Horne A, Gamble G, Drury PL, Reid IR. The skeletal effects of pioglitazone in type 2 diabetes or impaired glucose tolerance: a randomized controlled trial. Eur J Endocrinol 2014:170:255-62
Public notes

Contacts
Principal investigator
Name 28212 0
A/Prof Andrew Grey
Address 28212 0
Department of Medicine
University of Auckland
Private Bag 92019
Auckland
new Zealand
Country 28212 0
New Zealand
Phone 28212 0
+6499234423
Fax 28212 0
Email 28212 0
[email protected]
Contact person for public queries
Name 11369 0
Dr Anne Horne
Address 11369 0
Osteoporosis Research Group
Department of Medicine
Level 3,
Support Building
Auckland City Hospital
Park Rd.,
Grafton,
Auckland
Country 11369 0
New Zealand
Phone 11369 0
64-9-3078970
Fax 11369 0
Email 11369 0
[email protected]
Contact person for scientific queries
Name 2297 0
A/Prof Andrew Grey
Address 2297 0
Department of Medicine
University of Auckland
Private Bag 92019
Auckland
Country 2297 0
New Zealand
Phone 2297 0
64-9-3737599, ext 84423
Fax 2297 0
Email 2297 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIThe skeletal effects of pioglitazone in type 2 diabetes or impaired glucose tolerance: a randomized controlled trial2013https://doi.org/10.1530/eje-13-0793
N.B. These documents automatically identified may not have been verified by the study sponsor.