Effect of Intermittent Pressure in Patients With PAD

Mechanistic Insights Into Changes in Blood Flow Following Application of Intermittent Negative Pressure

The study will evaluate the effect of intermittent negative pressure (INP) on peripheral arterial disease (PAD) patient vascular function and blood flow. Patients will be given either -40mmHg INP or -10mmHg INP which will act as a placebo. Healthy volunteers will be given -40mmHg INP to evaluate changes in vascular function and blood flow with INP in healthy physiology.

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Device: Active Intermittent Negative Pressure (INP); Device: Placebo Intermittent Negative Pressure (INP)

Detailed Description

Atherosclerosis occurs when blood supply to the lower limbs is restricted upon accumulation of fat in the arteries. Atheroslerosis in the lower limbs is termed peripheral arterial disease (PAD). The initial symptom is pain in the lower limbs followed by ulceration and gangrene. The literature has indicated that intermittent negative pressure (INP) can be used to reduce pain and facilitate wound healing. INP is a non-invasive technique that aims to increase arterial and skin blood flow in lower limbs and foot. This study aims to investigate the underlying mechanisms that are involved in changes in blood flow following application of INP. The Flow-Ox 'boot' will be used to apply INP for periods ranging from 4-8 weeks, for an hour twice per day, to the lower limb to determine the effects of INP on vascular function and blood flow. Specifically, vascular tests such as assessments of endothelial function, arterial stiffness, ankle-brachial pressure index (ABPI) and blood borne metabolic and inflammatory markers will be performed before and after INP application. A pain chart will be employed before and after INP application to determine whether there is any change in perception of pain felt by individuals who suffer from pain associated with lower limb arterial disease.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Dundee, United Kingdom
    • School of Medicine, University of Dundee, Ninewells Hospital & Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

PAD Patients:

• Age ≥ 18 years
• Attending vascular outpatient clinics or admitted in ward with PAD.
• ABPI <0.9

Healthy Volunteers:

• Age ≥ 18 years
• No current or previous significant cardiovascular illness
• Able to give written informed consent

Exclusion criteria

PAD Patients:

• Unable to give written informed consent
• Patients with deep venous thrombosis
• Pregnant women

Healthy Volunteers:

• Positive medical history of: Vascular diseases such as PAD, stroke, IHD, hypertension... etc.
• Haematological conditions such as hypercoagulability, deep venous thrombosis... etc.,
• Alcohol excess
• Unable to give written informed consent
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active PAD group; -40mmHg of Intermittent Negative Pressure (INP) for 4-8 weeks.	Device: Active Intermittent Negative Pressure (INP); Application of -40mmHg negative pressure on the lower limb
Experimental: Placebo PAD group; -10mmHg of Intermittent Negative Pressure (INP) for 4-8 weeks.	Device: Placebo Intermittent Negative Pressure (INP); Application of -10mmHg negative pressure on the lower limb
Experimental: Healthy Volunteers; -40 mmHg of Intermittent Negative Pressure (INP) for 5 days	Device: Active Intermittent Negative Pressure (INP); Application of -40mmHg negative pressure on the lower limb

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in microvascular blood flow	Microvascular blood flow measurement in foot using laser Dopper imaging.	Baseline, 1 day and 4-8 weeks
Change in microvascular endothelial function	Peak blood perfusion response to acetylcholine (ACh) delivered by iontophoresis will be measured using a laser Doppler imager.	Baseline, 1 day and 4-8 weeks
Change in arterial stiffness	Brachial pulse wave analysis (PWA) augmentation index (Ax) and carotid-femoral pulse wave velocity (m/s) (PWV) as an indication of arterial stiffness.	Baseline, 1 day and 4-8 weeks
Change in macrovascular endothelial function	Brachial endothelial function measured as change in brachial blood vessel diameter (%) upon shear stress.	Baseline, 1 day and 4-8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain score	Self-scoring of pain felt by patient on a visual analogue scale with 0 being no pain at all to 10 being the worst pain ever felt.	Baseline, 1 day and 4-8 weeks
Change in concentration of blood borne inflammatory and oxidative stress biomarkers	Concentration of inflammatory and oxidative stress markers of endothelial activation/damage (including IL-1a, IL-6, IL-10, TNF-a, CRP, E-selectin and sICAM-1) measured in serum and plasma collected from patient blood samples.	Baseline, 1 day and 4-8 weeks
Change in Ankle-Brachial Pressure Index (ABPI)	Brachial systolic pressure and ankle (dorsalis pedis) systolic pressure (mmHg) measured using Doppler probe. ABPI calculated as ankle systolic pressure divided by brachial systolic pressure. ABPI <0.9 = PAD, ABPI =>1.0 Normal.	Baseline, 1 day and 4-8 weeks

Collaborators and Investigators

• Sponsor: University of Dundee
• Investigators: Principal Investigator: Jody McIntosh, PhD student

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2019
• Primary Completion (Actual): June 5, 2021
• Study Completion (Actual): June 5, 2021

Study Registration Dates

• First Submitted: February 19, 2019
• First Submitted That Met QC Criteria: February 22, 2019
• First Posted (Actual): February 26, 2019

Study Record Updates

• Last Update Posted (Actual): August 6, 2021
• Last Update Submitted That Met QC Criteria: August 5, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: PAD
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: 1-014-18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No