Super-Rehab: Can we Achieve Coronary Artery Disease Regression?

Study Overview
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Brief Summary
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The Super Rehab: Can we Achieve Coronary Artery Disease Regression? (a feasibility study) proposes to test the use of a novel lifestyle intervention (Super Rehab), in addition to standard care, for patients with both coronary artery disease and metabolic syndrome. This is a feasibility study that will test study processes, enable optimisation of the intervention and provide data for power calculations to enable design of pivotal trials of the clinical effectiveness of Super Rehab.

Detailed Description
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In this research we will study the feasibility of a randomised controlled trial (RCT) of a novel lifestyle intervention (Super Rehab), in addition to usual care, for patients with established coronary artery disease (CAD) and metabolic syndrome. Increasing evidence has shown that CAD can not only be stabilised, but can in fact regress with treatments that include lifestyle interventions. This feasibility study will involve patients undergoing a clinically indicated coronary CT angiography (CCTA) scan who are found to have confirmed CAD with plaque causing a narrowing in at least one coronary artery of ≥25% of the lumen on their CTCA; have evidence of coronary inflammation (defined by an abnormal fat attenuation index (FAI) of > -70.1HU or with FAI score [relative to age and sex matched patients] ≥ 75th percentile in the left anterior coronary or right coronary artery or with FAI score ≥ 90th percentile in the circumflex coronary); have Metabolic Syndrome, defined as any 3 of: high abdominal waist circumference (≥94cm males, ≥80cm females), hypertension (≥130/85mmHg or on treatment), raised fasting glucose (≥5.6mmol/L or on diabetic treatment), low HDL (≤1mmol/L males, <1.3mmol/L females), and high triglycerides (>1.7mmol/L). Participants will be randomised to either Super Rehab and Usual Care or to continue Usual Care only. Super Rehab includes a combination of separate 1:1 supervised high-intensity exercise and dietary advice sessions, and the whole programme lasts 12 months. Participants in both arms will undergo imaging, fitness, clinical tests (including blood tests), and complete questionnaires on four occasions during the study, alongside short interim and detailed end-of-study interviews. The study will primarily assess key feasibility outcomes to guide a potential subsequent RCT, e.g. recruitment and retention rates and test the acceptability of the intervention and study processes. In addition, the study will provide baseline data for power calculations to support study design for the planned future RCT into the clinical effectiveness of Super Rehab in this patient group.

Official Title
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Super-Rehab: Can we Achieve Coronary Artery Disease Regression? (a Feasibility Study)

Conditions
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Coronary Artery Disease, Metabolic Syndrome

Intervention / Treatment
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* Behavioral: Super Rehab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CCTA demonstrating coronary artery disease with plaque causing a narrowing in at least one coronary artery of ≥ 25% stenosis and a evidence of coronary inflammation (defined by an abnormal fat attenuation index (FAI; defined as FAI > -70.1HU or with FAI score [relative to age and sex matched patients] ≥ 75th percentile in the left anterior coronary or right coronary artery or with FAI score ≥ 90th percentile in the circumflex coronary) Have Metabolic Syndrome, defined as any 3 of: high abdominal waist circumference (≥94cm males, ≥80cm females), hypertension (≥130/85mmHg or on treatment), raised fasting glucose (≥5.6mmol/L or on diabetic treatment), low HDL (≤1mmol/L males, <1.3mmol/L females), and high triglycerides (>1.7mmol/L). Exclusion Criteria: Coronary artery disease requiring revascularisation Unstable angina New York Heart Association class III/IV heart failure or severe left ventricular impairment Severe valve disease Significant cardiomyopathy (as assessed by screening Cardiologist) Severe hypertension (defined as blood pressure >180/120mmHg) Uncontrolled cardiac arrhythmia Previous aortic dissection Recent acute pulmonary embolus deep vein thrombosis, stroke or transient ischaemic attack Severe autonomic or peripheral neuropathy Acute systemic illness or fever Significant acute or chronic renal failure Pulmonary fibrosis or interstitial lung disease Physically unable to participate in exercise Previous myocardial infarction or coronary re-vascularisation Severe coronary calcification that precludes assessment of the coronary lumen on CCTA A clinically significant ECG abnormality at the screening visit, which in the opinion of the screening Cardiologist exposes the subject to risk by enrolling in the trial Pregnant or breastfeeding Current participation in another intervention based research study Inability to fully understand the verbal and written descriptions of the study and the instructions provided during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Patients randomized to Usual Care or Super Rehab plus Usual Care
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual Care<br>Patients will continue Usual Care, which will include aspirin, a statin and routine lifestyle advice | |
| Experimental: Super Rehab plus Usual Care<br>12-month Super Rehab programme plus Usual Care | Behavioral: Super Rehab<br>* A 12-month healthcare-delivered lifestyle intervention involving exercise and nutritional support<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish recruitment rate | A key feasibility outcome for a potential future randomised controlled trial will be to establish recruitment rates: defined as the proportion of eligible patients who accept the invitation to participate in the study. | Week 0 | 
| Establish retention rate | A key feasibility outcome for a potential future randomised controlled trial will be to examine retention: defined as the proportion of recruited participants who complete the study. | Month 15 | 
| Establish adherence | A key feasibility outcome for a potential future randomised controlled trial will be to examine adherence: defined as, for participants in the intervention arm, the proportion of offered sessions completed. | Month 12 | 
| Assess acceptability of the intervention | A key feasibility outcome for a potential future randomised controlled trial will be to examine the acceptability of the intervention (Super Rehab) to participants and clinicians. This will be assessed qualitatively by an end of study interview. | Month 12 | 
| Assess acceptability of the study design | A key feasibility outcome for a potential future randomised controlled trial will be to examine the acceptability of the study design. This will be assessed qualitatively by an end of study interview. | Month 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate data collection procedures | To confirm that all data collection procedures (clinical, intervention and health economic data points) are achievable. This will be assessed as a percentage of the total number data-points we attempt to collect. | Month 15 | 
| Assess the use of routine clinical data (combination of body mass index and HbA1c) for identifying coronary artery disease patients with metabolic syndrome | The percentage of patients recruited who meet international consensus metabolic syndrome diagnostic criteria that have a body mass index >28kg/m2 and an HbA1c >42mmol/mol. | Month 15 | 
| Establish preliminary data for coronary artery disease regression with this intervention assessed with the peri-coronary fat attenuation index | To obtain preliminary data for coronary artery disease regression with Super Rehab when assessed with peri-coronary fat attenuation index (mean change in control vs intervention arms), to inform power calculations for a future randomised controlled trial. | Month 12 | 
| Establish key characteristics required in intervention delivery | A qualitative analysis of interviews with the study Patient Advisory Group will report the key characteristics required in the intervention (Super Rehab) delivery for a successful future study. | Month 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lifestyle risk reduction, Exercise, Inflammation, Behavior modifications, Nutrition therapy, Diet, Feasibility studies, Cardiovascular disease