Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000674730
Ethics application status
Approved
Date submitted
11/06/2013
Date registered
20/06/2013
Date last updated
20/06/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Does a supervised exercise program for claudication have an adverse effect on immune, muscle and
endothelial function?
Scientific title
In patients with symptomatic lifestyle limiting intermittent claudication, does a 12 week treadmill based supervised exercise program result in changes in endothelial function, body composition and energy expenditure, monocyte subpopulations, apoptosis in muscles, lactadherin expression, and microRNA 92-a expression.
Secondary ID [1] 282646 0
nil
Universal Trial Number (UTN)
U1111-1144-2088
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral artery disease 289349 0
Intermittent Claudication 289350 0
Condition category
Condition code
Cardiovascular 289686 289686 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study participants will be identified through the regional claudication clinic and referred to a 12 week exercise program if suitable. Participants will undertake 1 hour of supervised treadmill exercise, twice per week for 12 weeks. The exercise will consist of walking on a treadmill at a speed and incline to bring on leg pain caused by intermittent claudication within 3-5 min. Participants will walk until the point of near maximal pain as per current consensus guidelines. Participants will also be prescribed current best medical therapy and receive advice on smoking cessation. For the first six weeks of the program, six consecutive lectures (30min once per week) by a vascular nurse (Topic: Basics of PAD), physiotherapist (Topic: The benefits of exercise), pharmacist (Topic: Understanding your medications), dietitian (Topic: Eating for cardiovascular health), occupational therapist (Topic: Goal setting, work simplification), and podiatrist (Topic: The importance of foot care.) will be presented.
Intervention code [1] 287315 0
Treatment: Other
Comparator / control treatment
N/A - This is a single group study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289773 0
Walking performance measured by pain-free walking distance and 6-minute walk test
Timepoint [1] 289773 0
Day 0 and Day 90
Primary outcome [2] 289774 0
Levels of apoptosis in symptomatic muscles using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining for apoptotic nuclei on formalin fixed paraffin-embedded muscle biopsies.
Timepoint [2] 289774 0
Day 0 and Day 90
Primary outcome [3] 289775 0
Local and whole body skeletal muscle and fat mass using Dual-energy X-ray absorptiometry (DEXA)
Timepoint [3] 289775 0
Day 0 and Day 90
Secondary outcome [1] 303215 0
Resting energy expenditure measured using indirect calorimetry
Timepoint [1] 303215 0
Day 0 and Day 90
Secondary outcome [2] 303216 0
Proportions of classical, intermediate and non-classical monocytes in peripheral blood using a FACSCanto II flow cytometer. Monocytes will be identified using a gating strategy incorporating side-scatter properties, CD86 and CD45 positivity. Sub-populations will be identified by setting quadrant gates on a CD14 and CD16 dot plot.
Timepoint [2] 303216 0
Day 0, Day 21 and Day 90
Secondary outcome [3] 303217 0
Level of expression of lactadherin mRNA and protein in symptomatic skeletal muscle using reverse transcription real-time PCR and Western blot assays.
Timepoint [3] 303217 0
Day 0 and Day 90
Secondary outcome [4] 303218 0
Level of expression of microRNA-92a in symptomatic skeletal muscle using reverse transcription real-time PCR
Timepoint [4] 303218 0
Day 0 and Day 90
Secondary outcome [5] 303219 0
Quality of life using Australian vascular quality of life index (AUSVIQUOL) questionnaire
Timepoint [5] 303219 0
Day 0 and Day 90
Secondary outcome [6] 303222 0
EndoPAT reactive hyperaemia index (RHI) using Itmar EndoPAT 2000
Timepoint [6] 303222 0
Day 0 and Day 90
Secondary outcome [7] 303223 0
Flow mediated dilatation (FMD) is measured using a SonoSite M-Turbo portable ultrasound and high resolution linear array to visualize the distal brachial artery after temporary forearm ischemia induced by inflating a manual sphygmomanometer cuff to 260mmHg for 5min. Following cuff deflation, the brachial artery dilatation is measured for 3min and is later analysed using the Brachial Artery Analyser software.
Timepoint [7] 303223 0
Day 0 and Day 90

Eligibility
Key inclusion criteria
Symptomatic peripheral arterial disease, namely intermittent calf claudication caused by PAD defined by imaging and ankle-brachial pressure index.
Informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
No symptomatic peripheral artery disease (normal ABPI or imaging).
Thigh and buttock claudication.
Exercise tolerance limited by neurological, cardio-pulmonary or rheumatological disability.
Therapeutic anticoagulation or blood dyscrasias.
Post menopausal women on hormone replacement therapy.
Premenopausal women
Critical limb ischemia (rest pain or tissue loss)
Inability to provide informed consent
Patients with recent (<12 months) history of peripheral vascular interventions for symptoms

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients are enrolled from the claudication clinic at the Repatriation General Hospital. This clinic receives referrals from the Adelaide Southern Health area for vascular surgical opinion of lower limb claudication symptoms. Patients deemed to potentially benefit from a supervised exercise program are offered enrollment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Non-randomised trial
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Results will be expressed as mean +/- SD. Differences in response to the exercise or training will be assessed with the paired t-test. Statistical significance will be accepted at p-value less than 0.05.

From out unit's experience mean change in pain free walking distance (PFWD) following our 12-week SEP was 44m (SD 80m). For paired t-test analysis with an alpha level of 0.05 and statistical power of 0.8 the required sample size is approximately 26. This is similar to sample size calculations based on published data indicating a range from 6 to 26

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/05/2013
Actual
20/05/2013
Date of last participant enrolment
Anticipated
31/12/2014
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 1099 0
Repatriation Hospital - Daw Park
Recruitment hospital [2] 1100 0
Flinders Medical Centre - Bedford Park

Funding & Sponsors
Funding source category [1] 287427 0
Hospital
Name [1] 287427 0
Department of Vascular Surgery
Flinders Medical Centre
Country [1] 287427 0
Australia
Primary sponsor type
Hospital
Name
Department of Vascular Surgery, Flinders Medical Centre
Address
Department of Vascular Surgery
Flinders Medical Centre
Flinders Drive
Bedford Park 5042
SA
Country
Australia
Secondary sponsor category [1] 286175 0
Individual
Name [1] 286175 0
Dr Simon Vun
Address [1] 286175 0
Department of Vascular Surgery
Flinders Medical Centre
Flinders Drive
Bedford Park 5042
SA
Country [1] 286175 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289408 0
Southern Adelaide Clinical HREC
Ethics committee address [1] 289408 0
The Flats G5 – Rooms 3 and 4
Flinders Drive
Flinders Medical Centre, Bedford Park SA 5042
Ethics committee country [1] 289408 0
Australia
Date submitted for ethics approval [1] 289408 0
Approval date [1] 289408 0
12/04/2013
Ethics approval number [1] 289408 0
139.10

Summary
Brief summary
Patients with lifestyle limiting intermittent claudication will be offered, in addition to best medical therapy, participation in a 12-week supervised exercise program consisting of two 1 hour sessions per week. The exercise prescription will be based on current evidence of treadmill walking to near maximal pain. They will also undergo two key assessments at baseline (day 0) and at day 90. This will consist of measurement of walking performance (PFWD and 6MWD), body composition (DEXA), resting energy expenditure (calorimetry), endothelial function (FMD and EndoPAT), monocytes and subpopulations (flow cytometry), levels of apoptosis, lactadherin mRNA and protein expression and microRNA-92a expression in ischemic and non-ischemic muscles of the symptomatic leg.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40646 0
Prof Ian Spark
Address 40646 0
Department of Vascular Surgery
Flinders Medical Centre
Flinders Drive
Bedford Park 5042
SA
Country 40646 0
Australia
Phone 40646 0
+61 8 8204 5445
Fax 40646 0
+61 8 8204 7106
Email 40646 0
[email protected]
Contact person for public queries
Name 40647 0
Dr Simon Vun
Address 40647 0
Department of Vascular Surgery
Flinders Medical Centre
Flinders Drive
Bedford Park 5042
SA
Country 40647 0
Australia
Phone 40647 0
+61 8 8204 2116
Fax 40647 0
+61 8 8204 7106
Email 40647 0
[email protected]
Contact person for scientific queries
Name 40648 0
Dr Simon Vun
Address 40648 0
Department of Vascular Surgery
Flinders Medical Centre
Flinders Drive
Bedford Park 5042
SA
Country 40648 0
Australia
Phone 40648 0
+61 8 8204 2116
Fax 40648 0
+61 8 8204 7106
Email 40648 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

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