Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001151921
Ethics application status
Approved
Date submitted
22/06/2020
Date registered
3/11/2020
Date last updated
14/01/2024
Date data sharing statement initially provided
3/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial to evaluate an intensive lifestyle program for reversal of coronary heart disease.
Scientific title
A randomised controlled trial to evaluate an intensive lifestyle program for reversal of coronary heart disease.
Secondary ID [1] 301772 0
None
Universal Trial Number (UTN)
Trial acronym
LIfestyle VulnErable PLaqUe Study (LIVEPLUS)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary Heart Disease 317977 0
Condition category
Condition code
Cardiovascular 316010 316010 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intensive lifestyle program (ILP) + Optimal medical therapy (OMT).

Participants in this group will receive OMT, which refers to continued communication and reviews from their cardiologist who will adjust medications as required over the course of the study. They will also receive IMT which involves 1 year of a 5:2 pesco-vegetarian diet, physical activity and mindfulness training. Participants will be educated, instructed, and monitored through a phone-app. Participants will have regular face-to-face or Zoom call contact with study a dietician, exercise physiologist, and a mindfulness coach who will monitor their progress through the app. Details of each aspect can be seen below:

5:2 PESCO-VEGETARIAN DIET: Participants will be provided with food from Marley Spoon, who will deliver freshly made meals for the first 4 weeks of the intervention. They will also work alongside the study dietitian to design their weekly meal plans and menus in order to transition into making their own food after the first 4 weeks. The aim will be to substitute meat with fish and processed and refined foods with a range of minimally processed plant-based foods. Individuals will be asked to fast on 2 non-consecutive days of the week, allowing 2 vegetable meals of around 2000 kJ per day for women and about 2500 kJ for men. Participants will meet with the study dietician in person for an initial appointment at baseline. They will then be offered zoom or face-to-face meetings (30-45mins) bi-weekly for the first 3 months and monthly thereafter. Strategies to implement the dietary changes, meal planning, healthy recipes and nutritional information will be covered during dietician appointments. Body weight will be monitored weekly to help assess if participants are compliant with the dietary intervention. Study volunteers will report their body weights to the dietitian on a weekly basis using the LIVEPLUS app.

PHYSICAL ACTIVITY: Participants will be given an individualised home-based programme which will be based on the following guidelines from the American College of Cardiology Foundation/American Heart Association to manage individuals with stable ischemic heart disease. We will individualise each participant’s home-based physical activity programme according to their baseline activity. To measure baseline activity, participants will wear a Fitbit physical activity tracker for 7 continuous days and will complete a PAR questionnaire. They will then receive an initial consultation with an exercise physiologist who will set up a personalised programme. The goal for all participants will be to reach at least 150 minutes of moderate-intensity aerobic physical activity per week within the first 3 months. Intensity will be prescribed and monitored using the Fitbit heart rate zones, using 220-age as a prediction of maximal heart rate. During the first 3 months, participants will have bi-weekly 30 min appointments via zoom or face-to-face with their exercise physiologist. If participants are asymptomatic during the first 3 months of physical activity intervention, the following 9 months (month 3-12) will aim to vary the prescription in terms of mode, duration and intensity. Participants will be offered monthly 30 minute sessions during these months which will be an opportunity for their physical activity coach to prescribe variations in their training. Symptomatic participants will follow the same prescription until symptoms abate with ongoing monthly review. The specific symptoms monitored will be hear rate response during physical activity (from Fitbit), and then subjective feelings from participants which include; chest pain, dizziness or light-headedness, shortness of breath, nausea.

MINDFULNESS: Mindfulness-Based Stress Reduction (MBSR) is a specific approach that integrates meditation and gentle hatha yoga and has been studied both clinically and using systematic reviews. MBSR has been shown to be an effective and safe means for reducing stress. We plan to implement this program over the course of our study, using the structure and content from the online free course https://palousemindfulness.com. Each session will be conducted one-on-one to foster an ongoing, attentive relationship with each participant. The first session will be conducted in person to establish a comfortable rapport, and the following 14 sessions will be conducted electronically to decrease study burden to participants. The purpose of the first session will be to introduce to the participants the physiological relationship between heart disease and mental heath, as well as the science behind how mindfulness helps to improve this relationship. We also will explain what mindfulness and mindfulness-based stress reduction are and provide an outline of the intervention they will receive over the course of one year. Over the following sessions, participants will receive training mindfulness, such as practices like the body scan, breathing exercises, such as slow breathing at 6 breaths/minute and diaphragmatic breathing, education in posture for seated meditation and gentle yoga, and classic gentle yoga poses. The mode of training will primarily be delivered through the study app and consist of modules with new mindfulness information for each month in text form, multiple choice questions to verify understanding, short videos that explain different techniques, and a log to record breathing exercises and mindfulness practice for each month. Discussions with the mindfulness coach over zoom to answer any questions also will be used. Various educational materials will be given to participants. Palouse guidelines will be incorporated. However, the Palouse course is designed for 8 weeks. Because this study will be for one year, we will add educational materials to each month to supplement to Palouse course. For example, we will supplement each month with breathing exercises that have been researched by Dr. Richard Brown, such as slow and diaphragmatic breathing, as well as with mindfulness and breathing techniques described by Goswami Kriyananda from the Temple of Kriya Yoga in Chicago. Education on the science behind self-compassion, social connectedness, happiness, and interpersonal relationships will be informed by the scientific literature. One module will be released to participants through the study app each month and will take about 30 minutes to complete. In addition to reading this educational content, the mindfulness component of the intervention will consist of about 10 minutes of breathing exercise 6 days/week and 20 minutes of mindfulness practice (e.g., body scan, gentle yoga, mantra) 3 days/week. Participants also will meet with the mindfulness coach over zoom once a month for open ended discussion about the educational content and practice for 5-30 minutes, depending on participant preferences on duration of the call
Intervention code [1] 317897 0
Lifestyle
Intervention code [2] 317898 0
Behaviour
Intervention code [3] 318064 0
Treatment: Drugs
Comparator / control treatment
Optimal medical therapy (OMT).

Participants will receive usual clinical care which includes continued communication and reviews from their cardiologist who will adjust medications as required over the course of the study. This group will also be encouraged to follow the American Heart Association Diet and Lifestyle Recommendations (https://www.heart.org/en/healthy-living/healthy-eating/eat-smart/nutrition-basics/aha-diet-and-lifestyle-recommendations). They will be given educational materials around this diet which will be developed by our team, but based on general advice and recommendation for this patient group. Control participant will also be given a Fitbit device and attend a dietitian appointment every 3 months either in person or zoom. During this appointment, the dietitian will go through the healthy eating recommendations and go through various recipe ideas. Control participants will also be offered the mindfulness programme at the end of the study. They will have access to all of the education materials developed for this programme but won't have access to a mindfulness coach.
Control group
Active

Outcomes
Primary outcome [1] 324212 0
Change in Low-attenuation plaque volume (mm3) at 12 months with respect to baseline level using CT angiography.
Timepoint [1] 324212 0
Baseline and at 12 months after randomisation.
Primary outcome [2] 324213 0
Change in Myocardial blood flow (ml/g/min) at 12-month with respect to baseline level using MRI.
Timepoint [2] 324213 0
Baseline and at 12 months after randomisation
Secondary outcome [1] 384077 0
Total atheroma volume (TAV, mm3) using CT angiography.
Timepoint [1] 384077 0
Baseline and at 12 months after randomisation
Secondary outcome [2] 384079 0
Flow-mediated dilatation (FMD) (%) using high-resolution ultrasound.
Timepoint [2] 384079 0
Baseline then 1,6,12 months after randomisation.
Secondary outcome [3] 384080 0
Carotid intima-media thickness (cIMT) (mm) using high-resolution ultrasound.
Timepoint [3] 384080 0
Baseline then 1,6,12 months after randomisation.
Secondary outcome [4] 384081 0
Pulse wave velocity (PWV) (m/s) using the SphygmoCor XCEL system
Timepoint [4] 384081 0
Baseline then 1,6,12 months after randomisation.
Secondary outcome [5] 384082 0
Augmentation Index (AI) (%) using the SphygmoCor XCEL system.
Timepoint [5] 384082 0
Baseline then 1,6,12 months after randomisation.
Secondary outcome [6] 384083 0
Heart rate variability (HRV): Low Frequency (LF) and High Frequency (HF) (ms2) using the Human Non-Invasive Blood Pressure System.
Timepoint [6] 384083 0
Baseline then 1,6,12 months after randomisation.
Secondary outcome [7] 384084 0
Liver fat density (%) using the MR proton density fat fraction (PDFF) technique.
Timepoint [7] 384084 0
Baseline and at 12 months after randomisation..
Secondary outcome [8] 384085 0
Total sleep time (mins) using the Nox-T3+ device by NoxMedical (Iceland), distributed by Temple Healthcare. Participants will wear the device overnight to assess sleep parameters.
Timepoint [8] 384085 0
Baseline and at 12 months after randomisation.
Secondary outcome [9] 384086 0
Sleep efficiency (%) using the Nox-T3+ device will be determined from total time spent asleep as a proportion of total time spent in bed.
Timepoint [9] 384086 0
Baseline and at 12 months after randomisation.
Secondary outcome [10] 386683 0
Sleep onset latency (SOL) using the Nox-T3+ device by NoxMedical (Iceland), distributed by Temple Healthcare.
Timepoint [10] 386683 0
Baseline and 12 months after randomisation.
Secondary outcome [11] 386684 0
Wake after sleep onset (WASO) using the Nox-T3+ device by NoxMedical (Iceland), distributed by Temple Healthcare.
Timepoint [11] 386684 0
Baseline and 12 months after randomisation.
Secondary outcome [12] 386705 0
Whole body fat mass (kg) measured by DEXA using our Hologic Discovery W Dual Energy X-Ray Absorptiometry Scanner.
Timepoint [12] 386705 0
Baseline and 12 months after randomisation.
Secondary outcome [13] 386706 0
Whole body fat-free mass measured by DEXA using our Hologic Discovery W Dual Energy X-Ray Absorptiometry Scanner
Timepoint [13] 386706 0
Baseline and 12 months after randomisation.
Secondary outcome [14] 386707 0
Bone mineral density (g/cm2) of the hip using DEXA.
Timepoint [14] 386707 0
Baseline and 12 months after randomisation.
Secondary outcome [15] 386709 0
Blood pressure will be assessed using the SphygmoCor XCEL device.
Timepoint [15] 386709 0
Baseline then 1,6,12 months after randomisation.
Secondary outcome [16] 386710 0
Composite outcome of blood lipids (triglycerides, LDL-C, HDL-C) quantified by venous sampling. .
Timepoint [16] 386710 0
Baseline then 1,6,12 months after randomisation.
Secondary outcome [17] 386712 0
Fasting glucose (mmol/L) from blood sample.
Timepoint [17] 386712 0
Baseline then 1,6,12 months after randomisation.
Secondary outcome [18] 386713 0
Fasting insulin (pmol/L) from blood sample.
Timepoint [18] 386713 0
Baseline then 1,6,12 months after randomisation.
Secondary outcome [19] 386715 0
Composite metabolic control: Glucose and insulin response to oral glucose tolerance test (75g) at 0,30,60,120 minutes.
Timepoint [19] 386715 0
Baseline and 12 months after randomisation.
Secondary outcome [20] 386716 0
Inflammation, assessed by composite outcome of of high-sensitivity C-reactive protein (hs-CRP) and Tumour Necrosis Factor Alpha (TNF-a) from venous blood.
Timepoint [20] 386716 0
Baseline then 1,6,12 months after randomisation.
Secondary outcome [21] 386717 0
Urinary levels of F2-isoprostane levels.
Timepoint [21] 386717 0
Baseline and 12 months after randomisation.
Secondary outcome [22] 386718 0
Aerobic capacity using the 6-minute walk test (6-MWT).
Timepoint [22] 386718 0
Baseline and 12 months after randomisation.
Secondary outcome [23] 388271 0
HbA1c quantified by venous sampling. .
Timepoint [23] 388271 0
Baseline then 1,6,12 months after randomisation.
Secondary outcome [24] 388272 0
Body mass (kg) using digital scales.
Timepoint [24] 388272 0
Baseline then 1,6,12 months after randomisation.
Secondary outcome [25] 388273 0
Height (cm) using a wall-mounted stadiometer
Timepoint [25] 388273 0
Baseline

Eligibility
Key inclusion criteria
• Presence of LAP on coronary CTA
• 18-80 years of age
• BMI greater than or equal to 22.0 kg/m2
• Able to give full informed consent
• Able to undergo all study evaluations and adhere to the rigors of the ILP intervention
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History or clinical manifestation of any other significant metabolic, hematologic, pulmonary, cardio- vascular, gastrointestinal, neurologic, immune, hepatic, renal, urologic disorders, or cancer that, in opinion of the investigator, would make the candidate ineligible for the study
• Non-MRI-compatible implanted devices or implants
• Estimated glomerular filtration rate (eGFR) less than 30mL/kg/1.73m2
• Inability to exercise via supine ergometer
• Claustrophobia
• Contraindications for adenosine: Sinus node disease (e.g. sick sinus syndrome, symptomatic sinus bradycardia), second- or third- degree heart blocks, unstable angina, bronchospasm (e.g. asthma), heart transplant recipient, history of seizure disorder
• Contraindications for glyceryl trinitrate: Known nitrate hypersensitivity, severe anaemia, severe aortic or mitral stenosis, hypotension defined as resting systolic blood pressure equal to 89 mmHg.
• Not suitable for CT coronary angiography due to contraindications
• Psychiatric or behavioural problems (history of drug and alcohol abuse, eating disorder)
• Breast feeding or pregnant women, or those intending to become pregnant before the scheduled end of the intervention
• Unwilling to be assigned at random to the ILP+OMT or OMT group
• Unwilling or unable to adhere to the rigors of the ILP intervention or evaluation schedule over the entire one-year period
• Concurrent participation in any other interventional study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be randomised using computer generated random numbers, via a web-based randomisation system. The statistician will design the randomisation schedule and the research co-ordinator will hold the allocation in sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Web based randomiser validated by statistician
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
This is a randomised two-arm study design with 2 continuous co-primary endpoints repeatedly measured at baseline and after 12-month follow-up. A total of 150 patients (75 in each arm) will provide 90% power to demonstrate the efficacy of either outcome. The sample size is based on a 2-by-2 repeated measures design using each of the co-primary outcomes, with a predicted 20% lost to follow up. Efficacy analyses will be conducted on the basis of ’intention to treat’ principle. The primary analysis will be performed using Analysis of Covariance (ANCOVA), adjusted for baseline values.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2021
Actual
23/02/2022
Date of last participant enrolment
Anticipated
31/01/2024
Actual
Date of last data collection
Anticipated
31/01/2025
Actual
Sample size
Target
150
Accrual to date
21
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 16961 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 30621 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 306028 0
Charities/Societies/Foundations
Name [1] 306028 0
Australian Youth and Health Foundation
Country [1] 306028 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Camperdown NSW 2006
Country
Australia
Secondary sponsor category [1] 306491 0
None
Name [1] 306491 0
Address [1] 306491 0
Country [1] 306491 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306258 0
SLHD RPA ethics committee
Ethics committee address [1] 306258 0
Ethics committee country [1] 306258 0
Australia
Date submitted for ethics approval [1] 306258 0
18/05/2020
Approval date [1] 306258 0
22/07/2020
Ethics approval number [1] 306258 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103266 0
Prof Luigi Fontana
Address 103266 0
Level 5 West
D17 – Education and Research Hub
The Charles Perkins Centre
Camperdown
The University of Sydney
NSW
2006
Country 103266 0
Australia
Phone 103266 0
+61 2 8627 7499
Fax 103266 0
Email 103266 0
[email protected]
Contact person for public queries
Name 103267 0
Sophie Cassidy
Address 103267 0
Level 5 West
D17 – Education and Research Hub
The Charles Perkins Centre
Camperdown
The University of Sydney
NSW
2006
Country 103267 0
Australia
Phone 103267 0
+61 2 9114 4688
Fax 103267 0
Email 103267 0
[email protected]
Contact person for scientific queries
Name 103268 0
Sophie Cassidy
Address 103268 0
Level 5 West
D17 – Education and Research Hub
The Charles Perkins Centre
Camperdown
The University of Sydney
NSW
2006
Country 103268 0
Australia
Phone 103268 0
+61 2 9114 4688
Fax 103268 0
Email 103268 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Non-identifiable participant data will be shared based upon the research proposal and subsequent discretion of the Principal Investigator. This will include all data.
When will data be available (start and end dates)?
Data will be available after completion of the study (2025) and there will be no end date.
Available to whom?
Researchers can contact the PI if they have a research idea. The Principal Investigator will decide to release data based upon the proposal.
Available for what types of analyses?
This will depend on the research proposal and discretion of the Principal Investigator
How or where can data be obtained?
Contact the Principal Investigator by email ([email protected])


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.