High Intensity Interval Training In pATiEnts With Intermittent Claudication (INITIATE)

High Intensity Interval Training In pATiEnts With Intermittent Claudication (INITIATE): a Proof-of-concept Prospective Cohort Study to Assess Acceptability, Feasibility and Potential Clinical Efficacy

This INITIATE study evaluates the use of high-intensity interval training as a treatment modality for patients with intermittent claudication - an ambulatory leg pain caused by narrowed arteries that supply the lower limbs.

It is an observational cohort study considering HIIT as a treatment for intermittent claudication, consisting of two workstreams. Workstream 1: an initial observational cohort study to consider the feasibility of the intervention and exclusion criteria. Workstream 2: a proof of concept study utilising the altered intervention and exclusion criteria following recommendations highlighted during workstream 1.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Arterial Disease; Intermittent Claudication
• Intervention / Treatment: Other: High-intensity interval training

Detailed Description

Patients with peripheral vascular disease (PVD) may develop a reproducible pain in their legs when they walk, which usually subsides with rest. This is known as intermittent claudication (IC) and is caused by a reduced blood supply to the legs as a result of narrowed or hardened arteries that supply the lower limbs. This ambulatory pain impedes on activities of daily living, functional capacity and quality of life.

NICE clinical guidance recommends a 12-week supervised exercise programme as first-line treatment for IC, whereby patients are encouraged to walk to the point of maximal pain. Robust clinical trials have demonstrated that supervised exercise programmes are efficacious for improving both pain-free and maximal walking distances, whilst also potentially improving quality of life.

Despite this, supervised exercise programmes are vastly under-utilised and not always available to consultant vascular surgeons. This means that further programmes need to be developed in order to provide a range of options to patients to improve uptake and adherence rates. One such programme is a 6-week high-intensity interval training programme.

An initial observational cohort study of the 6 week HIIT programme will be conducted to determine to determine the feasibility of the intervention and inclusion criteria. The results from this will be used to make any necessary changes to the HIIT intervention before moving into a proof of concept study, considering the utility, safety, acceptability and potential clinical efficacy of this programme.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sean Pymer, MSc; Phone Number: 01482 674643; Email: sean.pymer@hey.nhs.uk

Study Locations

• United Kingdom
  • Hull, United Kingdom, HU3 2JZ
    • Recruiting
    • Academic Vascular Surgical Unit, Vascular Dept. 1st Floor Tower Block
    • Contact: Sean Pymer, MSc
    • Principal Investigator: Sean Pymer, MSc
    • Sub-Investigator: George E Smith, MD
    • Sub-Investigator: Amy E Harwood, PhD
    • Sub-Investigator: Lee Ingle, PhD
    • Sub-Investigator: Ian C Chetter, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Workstream 1

Inclusion criteria:

• Aged >18 years
• ABPI <0.9 at rest or a systolic pressure drop of ≥20mmHg at the ankle after exercise testing
• Ability to walk unaided
• English speaking and able to comply with exercise instructions

Exclusion criteria:

• Unable to provide informed consent
• Critical limb threatening ischaemia / rest pain / tissue loss
• Active cancer treatment
• Significant comorbidities precluding safe participation in exercise testing and / or training according to the American College of Sports Medicine (ACSM) guidelines (28)
• Resting/uncontrolled tachycardia (>100bpm) and/or resting/uncontrolled hypertension (systolic blood pressure >180mmHg or diastolic blood pressure >100mmHg)
• Symptomatic hypotension

Additional exclusion criteria:

Following baseline CPET, patients will be withdrawn and prevented from continuing their involvement in the study if there is any evidence of:

• Exercise-induced myocardial ischaemia or significant haemodynamic compromise (manifesting as anginal symptoms, significant ECG changes or an abnormal blood pressure response).
• An inability to complete a maximal effort CPET

Workstream 2:

Inclusion criteria:

• Aged >18 years
• ABPI <0.9 at rest or a systolic pressure drop of ≥20mmHg at the ankle after exercise testing
• Ability to walk unaided
• English speaking and able to comply with exercise instructions

Exclusion criteria:

• Unable to provide informed consent
• Critical limb threatening ischaemia / rest pain / tissue loss
• Active cancer treatment
• Significant comorbidities precluding safe participation in exercise testing and / or training according to the American College of Sports Medicine (ACSM) guidelines (28)
• Resting/uncontrolled tachycardia (>100bpm) and/or resting/uncontrolled hypertension (systolic blood pressure >180mmHg or diastolic blood pressure >100mmHg)
• Symptomatic hypotension

Additional exclusion criteria:

Following baseline CPET, patients will be withdrawn and prevented from continuing their involvement in the study if there is any evidence of:

● Exercise-induced myocardial ischaemia or significant haemodynamic compromise (manifesting as anginal symptoms, significant ECG changes or an abnormal blood pressure response).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Intensity interval training; High-intensity interval training performed for 20 minutes, 3 times weekly for a period of 6 weeks at 85-100% of maximal heart rate.	Other: High-intensity interval training; a high-intensity interval training programme completed 3 times a week for 6 weeks using a stationary Wattbike.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Events Recorded	Defined as the occurrence of any adverse or serious adverse events.	From enrolment to completion of 12-week follow-up
Tolerability Test	Defined by examining the patients ability to achieve and maintain exercise at the appropriate intensity for the duration of each session and examining reasons for withdrawal and whether or not they were related to the intervention. Tolerability will also consider the number of patients able to achieve a maximal effort CPET.	From the first to last exercise session, i.e. from week 0 to week 6.
Feasibility Test	Feasibility measures included the number of patients screened vs. the number eligible, the number of patients eligible vs. the number recruited and the number recruited vs. the number completed.	From study opening to recruitment to completion of last patient last visit i.e. 29 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptability testing	An evaluation of the acceptability of the exercise intervention assessed by patient feedback, using semi-structured interviews.	post-intervention follow-up, i.e. week 6.
Maximum walking distance	assessment of the distance that the patient can currently walk before having to stop due to claudication pain.	Baseline, post-intervention (week 6), then 4 weeks (week 10) and 12 weeks (week 18) post-intervention.
Pain-free walking distance	assessment of the distance that the patient can currently walk before experiencing claudication pain.	Baseline, post-intervention (week 6), then 4 weeks (week 10) and 12 weeks (week 18) post-intervention.
Physiological parameters	Physiological variables via cardiopulmonary exercise test to assess peak oxygen uptake and ventilatory anaerobic threshold	Baseline, post-intervention (week 6), then 4 weeks (week 10) and 12 weeks (week 18) post-intervention.
Quality of Life Questionnaire SF-36	Patient reported quality of life using the SF-36 SF-36 is a 36-Item Short Form Health Survey questionnaire. It consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability.	Baseline, post-intervention (week 6), then 4 weeks (week 10) and 12 weeks (week 18) post-intervention.
Quality of Life Questionnaire - VascuQol	Patient reported quality of life using VascuQoL VascuQol is a Vascular specific QoL tool, It measures across 4 domains and gives a total score ranging from 0-7 with a higher score indicating better Vascular specific quality of life.	Baseline, post-intervention (week 6), then 4 weeks (week 10) and 12 weeks (week 18) post-intervention.
Ankle-Brachial Pressure Index	The index or ratio of the pressure in the ankle compared with the arm.	Baseline, post-intervention (week 6), then 4 weeks (week 10) and 12 weeks (week 18) post-intervention.

Collaborators and Investigators

• Sponsor: Hull University Teaching Hospitals NHS Trust
• Collaborators: University of Hull
• Investigators: Principal Investigator: Sean Pymer, MSc, Academic Vascular Surgical Unit, Hull York Medical School

Publications and helpful links

General Publications

• Pymer S, Palmer J, Harwood AE, Ingle L, Smith GE, Chetter IC. A systematic review of high-intensity interval training as an exercise intervention for intermittent claudication. J Vasc Surg. 2019 Dec;70(6):2076-2087. doi: 10.1016/j.jvs.2019.03.050. Epub 2019 Jun 27.
• Pymer S, Ibeggazene S, Palmer J, Smith GE, Harwood AE, Carroll S, Ingle L, Chetter IC. Considering the Feasibility, Tolerability, and Safety of High-Intensity Interval Training as a Novel Treatment for Patients With Intermittent Claudication. J Cardiopulm Rehabil Prev. 2021 May 1;41(3):188-193. doi: 10.1097/HCR.0000000000000551.
• Pymer S, Harwood A, Ibeggazene S, McGregor G, Huang C, Twiddy M, Nicholls AR, Ingle L, Carroll S, Long J, Rooms M, Chetter IC; INITIATE investigator group. High INtensity Interval Training In pATiEnts with intermittent claudication (INITIATE): protocol for a multicentre, proof-of-concept, prospective interventional study. BMJ Open. 2020 Jul 6;10(7):e038825. doi: 10.1136/bmjopen-2020-038825.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2018
• Primary Completion (Anticipated): October 28, 2022
• Study Completion (Anticipated): December 28, 2022

Study Registration Dates

• First Submitted: July 11, 2019
• First Submitted That Met QC Criteria: July 31, 2019
• First Posted (Actual): August 1, 2019

Study Record Updates

• Last Update Posted (Actual): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Exercise; High-intensity interval training; interval training
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases; Intermittent Claudication
• Other Study ID Numbers: R2219

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