Intermittent Negative Pressure to Improve Blood Flow in Patients With Peripheral Artery Disease: Effects After Long-term Treatment

Study Overview
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Brief Summary
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Studies have shown that intermittent negative pressure (INP) can induce short-term increase in blood flow in the extremity in patients with peripheral artery disease (PAD). Case reports also have indicated that INP treatment has beneficial hemodynamic and clinical effects in patients with lower limb ischemia and hard to heal leg ulcers. However, the clinical and physiological effects of long-term INP treatment are not well documented and needs further investigation.

Detailed Description
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A double-blinded randomized sham-controlled trial. Otivio AS is the developer of FlowOx, a noninvasive CE marked device to increase blood flow to the lower extremity. The device acts as a pressure chamber sealed around the patient's lower leg, applying pulses of intermittent negative pressure and atmospheric pressure. The pressure pulses are generated by a control unit, alternating between removing air from- and venting the pressure chamber. Preliminary tests indicate a significant increase in blood flow to the extremity during INP treatment at -40 mmHg, but a similar increase in blood flow was not detected during treatment INP treatment at -10 mmHg. Hence, treatment with -10 mmHg, may serve as a sham intervention, when evaluating the clinical and physiological effects of long-term INP treatment. All patients will receive best medical treatment including advice for smoking cessation, dietary advice, and advice for physical exercise, and pharmacological treatment with statins and platelet inhibitors. Patients will be randomized into two groups, one group receiving INP treatment with a pressure of -10 mmHg, the other group receiving INP treatment with a pressure of -40 mmHg. Treatment will be conducted by the patient him/herself at home, one hour in the morning and one hour in the evening for 12 weeks. Pain-free- and maximal walking distance, ankle-brachial index, arterial blood flow during application of INP, maximal blood flow, and biomarkers of inflammation and endothelial dysfunction will be registered at baseline and after 12 weeks to evaluate the effects of long-term INP treatment.

Official Title
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Intermittent Negative Pressure to Improve Blood Flow in Patients With Peripheral Artery Disease: Effects After Long-term Treatment

Conditions
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Peripheral Arterial Disease, Intermittent Claudication

Intervention / Treatment
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* Device: FlowOx


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ankle-Brachial Index < 0,9, and intermittent claudication Exclusion Criteria: Incapable to make an informed consent Inability to perform a treadmill test Inability to independently operate FlowOx Severe heart disease such as unstable angina pectoris, severe heart failure (NYHA IV), severe valve failure Severe COPD

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blinded randomized sham-controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: INP -10mmHg<br>In addition to standard medical treatment, patients will receive treatment with FlowOx, applying intermittent negative pressure of -10mmHg one hour in the morning and one hour in the evening at home for 12 weeks. | Device: FlowOx<br>* FlowOx is a CE marked device developed to increase blood flow to the lower extremities. A pressure chamber is sealed around the leg below the knee and is connected to a control unit which induces pulses of 10 sec negative pressure, and 7 sec of atmospheric pressure.<br>|
| Active Comparator: INP -40mmHg<br>In addition to standard medical treatment, patient swill receive treatment with FlowOx, applying intermittent negative pressure of -40mmHg one hour in the morning and one hour in the evening at home for 12 weeks. | Device: FlowOx<br>* FlowOx is a CE marked device developed to increase blood flow to the lower extremities. A pressure chamber is sealed around the leg below the knee and is connected to a control unit which induces pulses of 10 sec negative pressure, and 7 sec of atmospheric pressure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in maximal walking distance | Treadmill test | At baseline and after 12 weeks of treatment | 
| Change in pain-free walking distance | Treadmill test | At baseline and after 12 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum levels of markers of inflammation and endothelial dysfunction | E-selectin, ICAM-I, IL1, IL-6, IL-8, TNF-alfa, TGF-beta, IL-10 | At baseline and after 12 weeks | 
| Changes in resting and maximal blood flow | Strain-gauge plethysmography | At baseline and after 12 weeks | 
| Changes in Ankle-Brachial Index |  | At baseline and after 12 weeks | 
| Changes in arterial blood flow during application of INP | Ultrasound | At baseline and after 12 weeks |