The Effect of Different Forms of Exercise on Both the Clinical, Systemic and Local Biological Responses in Intermittent Claudication
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Flinders University
- Enrollment
- 35
- Locations
- 2
- Primary Endpoint
- Improvement in Pain Free Walking Distance
Study Overview
Brief Summary
Cardiovascular disease remain one of the leading causes of death in Australia, accounting for 47637 (36%) of deaths in 2004.
Peripheral arterial disease (PAD) is a category of cardiovascular disease, characterised by intermittent claudication. This is defined as walking induced pain, cramping, aching, tiredness or heaviness in one or both legs that does not go away with continued walking and is relieved with rest. It is estimated that between 5-10% of individuals aged over 50 years suffer from claudication. The primary and most effective treatment for these patients is focused on improving walking ability and functional status.
Current research has shown that approximately 30% of patients improve with exercise, while 30% continue to deteriorate and the rest show no change. The changes produced at a biochemical and cellular level due to exercise are unknown. To help better understand this, our study will assess the entire range of proteins expressed before and after exercise in the skeletal muscle tissue of patients with intermittent claudication. This will help to identifying key proteins that have a role in improving patient symptoms and outcome.
Detailed Description
Why is this clinical problem important?
Peripheral Arterial Disease (PAD) is a major health problem in Australia, with a prevalence of 15% in males aged over 65 years. The direct health care cost of PAD in Australia was $180m in 1994, of which 78% was associated with hospitalisations. PAD is also a marker for advanced cardiovascular disease (CVD) involving coronary, cerebral, renal and aortic vessels; with a 2-3 fold increased risk of CVD-related mortality. In 2006-2007, 25,813 hospitalizations and 2,163 deaths were a result of PAD (Australian Institute of Health and Welfare 2009). The ageing Australian population and the prevalence of PAD increases (Australian Institute of Health and Welfare 2009), the national annual health expenditure on cardiovascular disease is likely to increase, greatly exceeding the 5.4 billion dollars spent in 2000-01 (Australian Bureau of Statistics 2006). The most frequent symptom of mild to moderate PAD is intermittent claudication (IC), defined as walking-induced pain and cramping in one or both legs (most often calves) that is relieved with rest. The primary and most effective treatment for people with intermittent claudication is focused on improving walking ability and functional status.
What is already known about the effect of exercise in intermittent claudication?
The beneficial effects of exercise training as a treatment have been confirmed in several randomised controlled trials. The optimum form of exercise still hasn't been elucidated. The mechanisms of improvement of claudication with exercise are largely unknown. Although exercise stimulates an ischaemic-reperfusion (I-R) insult, repetitive exercise may produce an adaptive response to this I-R insult. Other potential themes include effect of exercise on stimulating or inhibiting angiogenesis and/or muscle protein synthesis.
Although the principal cause of IC is reduced blood flow to the lower limbs relative to increased demand during exercise, the pathophysiology of IC is not completely understood. For example, limb haemodynamics does not closely correlate with clinical presentation or the limitations in peak exercise performance. Haemodynamic measures of the severity of PAD, such as the ankle-brachial systolic blood pressure index (ABI) and blood flow by strain gauge plethysmography, are poor predictors of exercise capacity in patients with IC.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •All claudicants with a walking distance of 50 metres or more with a resting ankle brachial index equal to or less than 0.
- •Claudicants meeting above criteria, who may have previously had a percutaneous arterial intervention for symptom control more than 12 months ago.
Exclusion Criteria
- •Patients with lower limb pain of other aetiologies - neurogenic claudication evidenced by normal ankle brachial indices and duplex ultrasound.
- •Patients with lower limb ischaemic rest pain
- •Patients with current or previous tissue loss, such as ulcers or necrotic lesions.
- •Patients with recent (<12 months) history of peripheral vascular interventions for symptoms.
- •Patients with pre-existing cardiac or respiratory problems limiting exercise.
- •Patients with previous disabling strokes which would restrict exercise regimes
- •Patients with anticoagulation or blood dyscrasias.
- •Women who are pre-menopausal,
- •Women receiving hormone-replacement therapy.
Outcomes
Primary Outcomes
Improvement in Pain Free Walking Distance
Time Frame: Change from baseline (pre intervention) to 12 weeks (post intervention)
Patients will be exercised based on standard protocols and monitored for improvements in Maximal walking distance and Pain Free Walking distances.
Secondary Outcomes
- Skeletal muscle protein expression(Change from baseline (pre intervention) to 12 weeks (post intervention))
- Inflammatory cytokines(Change from baseline (pre intervention) to 12 weeks (post intervention))
- Endothelial function(Change from baseline (pre intervention) to 12 weeks (post intervention))
Investigators
Christopher L Delaney
Doctor
Flinders University