Clinical trial NCT05075317: Time Restricted Eating and Cardiac Rehabilitation
Official title: Time Restricted Eating and Cardiac Rehabilitation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Coronary Artery Disease
Keywords: Time-Restricted Eating
Cardiac Rehabilitation
Cardiorespiratory Fitness
Caloric Restriction
Coronary Artery Disease
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: University Health Network, Toronto
First posted: 2021-10-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will use a form of intermittent fasting called time-restricted eating (TRE) where individuals consume ad libitum energy intake within a set window of time, commonly 8 hours, which induces a fasting window of 16 hours per day (i.e., 16:8 TRE). TRE could be an effective addition to cardiac rehabilitation as it has demonstrated cardiovascular health benefits and potential for synergy when combined with exercise training. This study will determine if TRE is a feasible and safe nutrition intervention during cardiac rehabilitation and if TRE improves the health benefits of cardiac rehabilitation compared to cardiac rehabilitation alone.

Detailed description: HYPOTHESIS

1. Cardiac rehabilitation and TRE will be feasible in terms of adherence to a 16-hour daily fast (≥70%, which would represent 5/7 days/week) and safe (no excess symptoms or adverse events)
2. Cardiac rehabilitation and TRE will provide added cardiovascular health benefits (improved VO2peak, reduced fat mass) compared to cardiac rehabilitation alone.

JUSTIFICATION: Past animal and human clinical trials have demonstrated TRE to be beneficial in realigning circadian rhythm, improve coronary artery disease (CAD) and peripheral artery disease (PAD) through the reduction in calorie intake, and promote cell signalling and repair pathways during the fasting period. TRE has not been tested in patients with CAD or other heart diseases but has shown to improve comorbid conditions (diabetes and hypertension) and improve metabolic profiles (blood pressure, hemoglobin A1c, fasting glucose, insulin sensitivity, and lipid profiles. Additionally, TRE when combined with exercise, such as in cardiac rehabilitation programs, improves VO2 peak and reduces fat mass compared to exercise alone. The proposed study will deliver a TRE intervention in combination with the cardiac rehabilitation program and is expected to be feasible, safe, and improve outcomes of cardiac rehabilitation.

OBJECTIVES: The primary aim of this study is to evaluate the feasibility (adherence) and safety (adverse events) of TRE in combination with cardiac rehabilitation.

The secondary aim is to assess the efficacy of the intervention on:

1. VO2peak, body composition, fasted glucose, hemoglobin A1c, blood pressure and waist circumference
2. Lifestyle behavioral change outcomes (dietary intake, dietary quality, physical activity, perceived stress)

4.Cardiac rehabilitation adherence

Exploratory aims of the study include identifying sex differences (equal recruitment of males and females) and participants' experience with TRE (including confidence in maintaining this eating pattern or modifications to increase adherence).

RESEARCH METHOD This study will be a two-site (Toronto Rehabilitation Institute and Toronto Western Hospital), 2-arm, parallel-group, randomized feasibility trial of cardiac rehabilitation alone or cardiac rehabilitation plus 16:8 TRE. Men and women who are referred through the standard clinical pathways for coronary artery disease and are willing to accept random assignment and complete the study assessments will be enrolled. Both groups will receive the standard, multi-dimensional cardiac rehabilitation program consisting of physician-directed risk factor management, an individualized exercise prescription, and virtual education. Participants randomized to the TRE group will be asked to eat only between 11 am and 7 pm for the duration of the cardiac rehabilitation program (\~16 weeks). Adherence will be collected via twice daily text messages asking participants to respond with the time they started and stopped eating. Safety will be collected by self-report and medical records. Efficacy outcomes will be assessed by cardiopulmonary exercise test, blood draw, dual x-ray absorptiometry, 3-day diet records, accelerometers, and questionnaires. Study outcomes will be measured at baseline and at the end of the cardiac rehabilitation program.

STATISTICAL ANALYSIS Participant characteristics will be summarized using descriptive statistics. For adherence, both the text message response rate and adherence rate to the 16-hour daily fast will be reported. The change in caloric intake, diet quality, physical activity and efficacy outcomes will be compared between groups by analysis of covariance with baseline values as covariates. Relative risk will be used to compare the incidence of safety outcomes between groups. The primary analysis will be intention to treat and performed with both sexes combined. Secondary analyses will be performed separately in each sex.

Eligibility criteria: Inclusion Criteria:

* Men and women who are referred and eligible for either the outpatient cardiac rehabilitation program for coronary artery disease or peripheral vascular disease
* willing to accept random assignment and complete the study assessments
* Equal numbers of men and women will be recruited

Exclusion Criteria:

* Inability to complete the consent form and communicate in English
* Self-reported history of an eating disorder
* Current or recent (1 year) pregnancy or breast feeding
* Body mass index \<18.5 kg/m\^2 or clinical signs of cachexia
* Contraindications or inability to perform cardiopulmonary exercise testing
* Type 1 diabetes
* Type 2 diabetes that requires exogenous insulin
* Working night or rotating shifts
* Eating window \<12 hours or consistently eating less than 3 meals/day in the past 3 months

Primary outcomes:
measure: Adherence to the daily ≥16-hour fast for the 16-weeks of the cardiac rehabilitation program.
timeFrame: Averaged over the 16 weeks of the intervention
measure: Cardiorespiratory fitness as measured by peak volume of oxygen consumption (VO2peak)
timeFrame: 16 weeks
measure: Fat mass
timeFrame: 16 weeks
Secondary outcomes:
measure: Symptoms from TRE
timeFrame: 16 weeks
measure: Seattle Angina Questionnaire score
timeFrame: 16 weeks
measure: Adverse events
timeFrame: 1-year
measure: Fat-free mass
timeFrame: 16 weeks
measure: Hemoglobin A1c
timeFrame: 16 weeks
measure: Blood pressure
timeFrame: 16 weeks
measure: Waist circumference
timeFrame: 16 weeks
measure: Fasted blood glucose
timeFrame: 16 weeks
measure: Metabolic syndrome
timeFrame: 16 weeks
measure: Lipid profile
timeFrame: 16 weeks
measure: Health-related quality of life measured by the RAND-36 Physical Component Summary
timeFrame: 16 weeks
Other outcomes:
measure: Macronutrient ratios
timeFrame: 16 weeks
measure: Caloric intake
timeFrame: 16 weeks
measure: Cardiac rehabilitation adherence
timeFrame: 16 weeks
measure: Time-restricted eating experience
timeFrame: 16 weeks
measure: Mediterranean Diet Score
timeFrame: 16 weeks
measure: Physical activity and sedentary time
timeFrame: 16 weeks
Locations:
city: Toronto
country: Canada
facility: Toronto Rehabilitation Institute, University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Paul Oh, MD
role: STUDY_DIRECTOR
affiliation: University of Toronto, KITE Research Institute
name: Amy Kirkham, PhD
role: PRINCIPAL_INVESTIGATOR
References: