Addressing Individual Variability in Response to Exercise

In this proposal, the investigators challenge the assumption that following the physical activity guidelines implies benefit for ALL adults, and that if benefit is not achieved in response to first line therapy, it will be by simply exercising more. Thus, for improving cardiorespiratory fitness and cardiometabolic risk factors, unanswered questions include: 1) To what extent, regardless of exercise amount or intensity, is exercise not associated with benefit? Demonstration of a resistance to benefit through exercise in a substantial number of adults would be a novel and important finding, would counter the assumptions of many if not most health care practitioners, and could have immediate and direct application in all health care settings. 2) To what extent will non-responders to first line therapy (150 min/wk) be required to increase exercise amount or intensity to achieve benefit? 3) To what extent will failure to improve CRF segregate (be associate with) with cardiometabolic risk factors? The investigators propose that adults who remain exercise resistant for improvement in CRF and cardiometabolic risk despite increasing amount or intensity are at high risk of metabolic disease and consequently, are candidates for alternative treatment strategies. 4) To what extent is biological sex and/or phenotype a determinant of response or non-response to exercise?

Study Overview

• Status: Withdrawn
• Conditions: Exercise; Cardiorespiratory Fitness
• Intervention / Treatment: Other: Exercise

Detailed Description

The trial has three objectives:

Primary objective: Determine whether alterations in exercise amount and intensity improves the rate of clinically meaningful improvements in aerobic exercise capacity as measured by cardiorespiratory fitness (CRF, VO2peak) among adults.

Secondary objective: Determine whether common cardiometabolic risk factors segregate with respect to variation in CRF to first line therapy in adults, and, whether clinically meaningful improvements in cardiometabolic risk factors segregate with associated improvement in CRF.

Tertiary objective: Identify whether biological sex and/or phenotype are determinants of variation in CRF and cardiometabolic risk factors in response to first line therapy, and, whether they predict variability in CRF response to alterations in exercise dose.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Sedentary lifestyle (planned physical activity for one day per week or less).
• Weight stable (± 2 kg) for 6 months prior to the beginning of the study.
• BMI between 20 and 40 kg/m2.

Exclusion Criteria:

• Physical impairment which would make the intervention very difficult or unsafe according to doctor's advice.
• Diabetes, current smokers.
• Plan to move from the area in next 8 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control
Experimental: Low amount, low intensity	Other: Exercise; Participants will exercise under supervision. Exercise dose will vary by amount and intensity
Experimental: Low amount, high intensity	Other: Exercise; Participants will exercise under supervision. Exercise dose will vary by amount and intensity
Experimental: High Amount, low intensity	Other: Exercise; Participants will exercise under supervision. Exercise dose will vary by amount and intensity
Experimental: High Amount, high intensity	Other: Exercise; Participants will exercise under supervision. Exercise dose will vary by amount and intensity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cardiorespiratory Fitness	Cardiorespiratory fitness will be determined using direct (open circuit spirometry) measures of oxygen consumption (expressed in L/min) obtained during a maximal treadmill test.	Measured at baseline and every 4 weeks for 32 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cardiometabolic risk factors	Fasting glucose (mmol/L)	Measured at baseline, 16 and 32 weeks.
Change in cardiometabolic risk factors	Fasting LDL- and HDL-cholesterol (mmol/L)	Measured at baseline, 16 and 32 weeks.
Change in cardiometabolic risk factors	fasting insulin (pmol/L)	Measured at baseline, 16 and 32 weeks.
Change in cardiometabolic risk factor	fasting triglycerides (mmol/L)	Measured at baseline, 16 and 32 weeks.

Collaborators and Investigators

• Sponsor: Dr. Robert Ross
• Collaborators: Canadian Institutes of Health Research (CIHR)

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): April 1, 2026
• Study Completion (Anticipated): April 1, 2026

Study Registration Dates

• First Submitted: February 28, 2020
• First Submitted That Met QC Criteria: March 7, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 22, 2022
• Last Update Submitted That Met QC Criteria: June 16, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: Ross2019

Drug and device information, study documents

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