Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01799057




Registration number
NCT01799057
Ethics application status
Date submitted
22/02/2013
Date registered
26/02/2013
Date last updated
9/02/2016

Titles & IDs
Public title
The Effects of Metformin on Functional Capacity in Individuals With Peripheral Artery Disease-Related Intermittent Claudication
Scientific title
Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study of Metformin for the Assessment of Changes in Functional Capacity, Endothelial Function, and Hemodynamics in Individuals With Peripheral Artery Disease-Related Intermittent Claudication
Secondary ID [1] 0 0
493/12
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral Arterial Disease 0 0
Intermittent Claudication 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Metformin
Treatment: Drugs - Placebo

Experimental: Metformin - Metformin at a maximum dose of 1000mg twice daily for 16-18 weeks (i.e. maximum of 2000mg per day).

Placebo comparator: Placebo - Matching placebo twice daily for 16-18 weeks.


Treatment: Drugs: Metformin
Participants randomized to metformin will be treated at a maximum dose of 2000mg per day (i.e. 1000mg twice daily for 16-18 weeks; up-titrated from 500mg twice daily for the first 2 weeks). Participants may complete the 16-18 week treatment intervention at the lower dose of 500mg twice daily if limited by side effects.

Treatment: Drugs: Placebo
Participants randomized to placebo will take matching oral capsules according to the same dose schedule specified for the metformin intervention.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in pain-free walking time
Timepoint [1] 0 0
Measured at baseline and following 16-18 weeks treatment
Primary outcome [2] 0 0
Change in maximum walking time
Timepoint [2] 0 0
Measured at baseline and following 16-18 weeks treatment
Secondary outcome [1] 0 0
Change in questionnaire-based markers of quality of life / perceived functional capacity
Timepoint [1] 0 0
Measured at baseline and following 16-18 weeks treatment
Secondary outcome [2] 0 0
Change in endothelial function
Timepoint [2] 0 0
Measured at baseline and following 16-18 weeks treatment
Secondary outcome [3] 0 0
Change in skeletal muscle blood flow response to insulin
Timepoint [3] 0 0
Measured at baseline and following 16-18 weeks treatment
Secondary outcome [4] 0 0
Change in skeletal muscle blood flow response to acute exercise
Timepoint [4] 0 0
Measured at baseline and following 16-18 weeks treatment
Secondary outcome [5] 0 0
Change in insulin sensitivity
Timepoint [5] 0 0
Measured at baseline and following 16-18 weeks treatment
Secondary outcome [6] 0 0
Change in objectively measured physical activity / sedentary behaviour in the daily life setting.
Timepoint [6] 0 0
Measured at baseline and following 16-18 weeks treatment

Eligibility
Key inclusion criteria
* Age =40 years old.
* Resting ankle-brachial index (ABI) =0.90 in the limiting leg(s), or a >20% reduction in the ABI measured immediately post-exercise where the resting ABI is >0.90. In cases of incompressible arteries in the limiting leg(s) (i.e. ABI =1.40), a toe-brachial index (TBI) of =0.70 is required.
* Peripheral artery stenosis/occlusion in the limiting leg(s), documented by duplex ultrasonography or other imaging tests.
* Stable (i.e. 3-month history) intermittent claudication in at least one PAD-affected leg.
* Maximum walking time during graded treadmill exercise testing (Gardner-Skinner protocol) =1 minute and =16 minutes.
* Concurrent medications that may affect primary, secondary or exploratory endpoints have remained stable over the previous 3 months.
* Have given signed informed consent to participate in the study.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Identification of any other medical condition requiring immediate therapeutic intervention.
* Clinically significant abnormal electrocardiogram (ECG) at rest or during exercise that represents a contraindication to study procedures or the study drug.
* Myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft surgery (CABG), or other major surgery within the previous 6 months.
* Exercise capacity limited by a factor other than PAD-related intermittent claudication.
* Any condition that precludes valid completion of a treadmill exercise test.
* Critical limb ischemia in either leg, defined as PAD-related chronic ischemic rest pain or skin lesions (ulcers, gangrene).
* Previous peripheral revascularisation or other surgical treatment for PAD in the previous 6 months.
* Known non-atherosclerotic cause of PAD.
* Active cancer.
* Uncontrolled hypertension (resting brachial blood pressure =160/100 mmHg).
* Evidence of pharmacologically-treated or poorly controlled (i.e. HbA1c =7.5%) type 2 diabetes or other class of diabetes (e.g. type 1 diabetes).
* Known intolerance or contraindication(s) to metformin.
* Known contraindication(s) to "Definity" (perflutren lipid microsphere).
* Participation or intention to participate in another clinical research study during the study period.
* History of non-compliance to medical regimens or unwillingness to comply with the study protocol.
* Any other condition that in the opinion of the Investigators would confound the evaluation and interpretation of the data.
* Persons directly involved in the execution of the protocol.
* Incapable of providing written informed consent due to cognitive, language, or other reasons.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2014
Sample size
Target
Accrual to date
Final
2
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Baker IDI Heart and Diabetes Institute - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Baker Heart and Diabetes Institute
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bronwyn A Kingwell, PhD
Address 0 0
Baker Heart and Diabetes Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

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

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT01799057