The Effect of Ischemic Conditioning on Strength and Ambulation in Subjects With PAD

Study Overview
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Brief Summary
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Lower limb amputation is common in the United States, with approximately 150,000 amputations annually. Most individuals walking with a prosthesis demonstrate asymmetrical loading-i.e., they favor the amputated side by placing more weight and increased ground reaction forces through the intact limb-which likely contributes to increased metabolic cost of walking. Lack of adequate muscular strength in the lower limb to attenuate these forces places increased stress on the joints, which may be displaced proximally, and may play a role in reported knee and hip pain in the intact limb. Lower limb muscle weakness following amputation has been well documented. Increasing quadriceps strength is important after an amputation because it is positively correlated with gait speed. Gait speed may also be associated with successful community mobility, which leads to improved quality of life following amputation. Individuals with amputation who resume an active lifestyle are able to maintain strength. However, these individuals represent a minority of persons with lower limb amputation; most individuals report more barriers than motivators to adopt an active lifestyle. Ischemic conditioning (IC) may strengthen leg muscles and reduce the metabolic cost of activity after amputation. In IC, the limb is exposed to brief, repeated bouts of ischemia (reduced blood flow) immediately followed by reperfusion. IC has been shown to improve muscle performance in healthy and diseased populations. IC has also been used more recently in patients with peripheral artery disease (PAD) as an intervention to improve function, such as walking ability. Acute exposure to IC increases muscle strength and activation, both in healthy, active individuals and in those with severe neuromuscular dysfunction, such as stroke survivors. IC also attenuates muscular fatigue. Increased fatigue resistance at submaximal contraction levels following IC may be due to increased neural activation of skeletal muscle. Changes in neural activation of muscle may be particularly beneficial during cortical reorganization after amputation. Reduced quadriceps fatigue during submaximal activities may also drive changes in gait kinematics, such as increased knee flexion during loading and mid-stance. Exposure to IC may also increase the oxidative properties of skeletal muscle, offering a direct pathway to reduce metabolic cost. Therefore, IC may lead to cellular changes that lower the metabolic cost of activity. The primary aim of this study is to quantify the benefits of acute and chronic IC on quadriceps strength and walking economy in individuals with PAD and history of lower limb amputation.

Official Title
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The Effect of Ischemic Conditioning on Strength and Ambulation in Subjects With Peripheral Artery Disease (PAD)

Conditions
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Peripheral Arterial Disease, Peripheral Vascular Disease, Amputation, Lower Limb Amputation Knee, Lower Limb Amputation Above Knee (Injury), Lower Limb Amputation Below Knee (Injury)

Intervention / Treatment
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* Procedure: Ischemic Conditioning Low - Sham Comparator
* Procedure: Ischemic Conditioning High - Active Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Able to ambulate independently without the use of aids (i.e., walking cane) Able to walk at least 10 minutes continuously without stopping History of diagnosed peripheral artery disease. For Amputees: History lower limb unilateral transtibial or transfemoral amputation. Exclusion Criteria: Inability to give informed consent neurological disorder that affects gait two or more falls within the previous 12 months currently pregnant (or intend to become pregnant while participating in study) history of any condition where fatiguing contractions or resisted leg contractions are contraindicated blood clots in the leg, or any condition in which compression of the thigh or transient ischemia is contraindicated (e.g. open wounds in the leg). history of hypertension history of heart failure Head injury within the previous 6 months Seizure disorder Adverse reaction to ultrasound gel History of thrombosis History of sickle cell trait

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Ischemic Conditioning Low<br>Blood flow restriction with low compression | Procedure: Ischemic Conditioning Low - Sham Comparator<br>* The use of a Hokanson rapid inflator cuff to restrict blood flow at 25mmHg for 5 minutes followed by a 5 minute reperfusion period, repeated for 5 cycles.<br>|
| Active Comparator: Ischemic Conditioning High<br>Blood flow restriction with high compression | Procedure: Ischemic Conditioning High - Active Comparator<br>* The use of a Hokanson rapid inflator cuff to restrict blood flow at 225mmHg for 5 minutes followed by a 5 minute reperfusion period, repeated for 5 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quadriceps strength | Quadriceps strength assessed by a Biodex dynamometer | through study completion, an average of 6 weeks | 
| Change in gait kinematics | Gait mechanics assessed by joint angles using Vicon cameras and reflective markers | through study completion, an average of 6 weeks | 
| Change in gait kinetics | Gait mechanics assessed by joint forces using a Bertec instrumented treadmill in combination with gait kinematics | through study completion, an average of 6 weeks | 
| Change in gait metabolics | Assessment of oxygen consumption during walking using a metabolic cart | through study completion, an average of 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six-minute walk test | Measurement of distance walked in six minutes | through study completion, an average of 6 weeks |