Improvements in Aerobic Fitness With Exercise Training: the Role of Myokines

NCT ID: NCT06141512

Last Updated: 2024-12-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-23
• Study Completion Date: 2025-06-01

Brief Summary

For both healthy adults and patients with cardiovascular disease (CVD), aerobic fitness (V̇O2max) is a stronger predictor of the risk of future chronic disease and premature death than other established risk factors such as hypertension, smoking, or Type 2 diabetes. It is important to improve the understanding of the regulation of V̇O2max to enable optimisation of interventions aimed at increasing V̇O2max in the current predominantly sedentary population. Currently, only exercise training is a viable method for increasing V̇O2max. However, ~10-20% of people who follow fully supervised, standardised training interventions do not demonstrate a measurable increase in V̇O2max. Low response to training is a clinically relevant concern, but the large variability in response to exercise training also provides an opportunity to dissect out the molecular mechanisms responsible for adaptations to V̇O2max by contrasting low vs. high responders to training. It has been previously demonstrated that low responders for VO2max fail to up regulate a number of genes that encode putative 'myokines', while the high responders demonstrated a significant increase in the expression of these genes, suggesting these myokines may play an important mechanistic role in modulating VO2max. The aim of the present study is to examine whether low responders for VO2max have an attenuated increase in the plasma levels of the previously identified myokines.

Detailed Description

For both healthy adults and patients with cardiovascular disease (CVD), aerobic fitness (V̇O2max) is a stronger predictor of the risk of future chronic disease and premature death than other established risk factors such as hypertension, smoking, or Type 2 diabetes. Considering the large medical and economic burden of physical inactivity-related chronic disease it is important to improve the understanding of the regulation of V̇O2max to enable optimisation of interventions aimed at increasing V̇O2max in the current predominantly sedentary population. Furthermore, there is a need to identify novel drug targets to aid pharmacological intervention in those individuals who are unwilling or unable to improve V̇O2max through exercise.

Currently, only exercise training is a viable method for increasing V̇O2max. However, although exercise training on average improves V̇O2max, ~10-20% of people who follow fully supervised, standardised training interventions do not demonstrate a measurable increase in V̇O2max. Low response to training is a clinically relevant concern, but the large variability in response to exercise training also provides an opportunity to dissect out the molecular mechanisms responsible for adaptations to V̇O2max by contrasting low vs. high responders to training.

Using this approach it has previously been shown that in skeletal muscle samples obtained pre- and post- training, 86 genes are differentially regulated in high compared to low responders for V̇O2max. Strikingly, out of these 86 genes, 13 genes encode proteins that have been reported to be released by muscle during or after exercise (i.e., 'messenger proteins' termed myokines). This strongly suggests low responders to exercise training fail to sufficiently upregulate the production and release of these myokines, and that this is (at least partly) the reason why these people do not manage to improve their V̇O2max as much as high responders. However, in order to confirm a mechanistic role of these myokines in increasing V̇O2max, it needs to be demonstrated that beside the change in gene expression, the change in the plasma levels of these myokines is also impaired in low responders for V̇O2max.

Conditions

General Health

Keywords

VO2max; Myokine; Cardiorespiratory Fitness

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Reduced-exertion high-intensity interval training (REHIT)

All participants complete 6 weeks (3 sessions/week) of an exercise intervention labelled 'REHIT'.

Exercise sessions involve 10 minutes of unloaded cycling interspersed with 2 x 20 sec 'all-out' sprints against a resistance of 7.5% of participant's body weight. Sprints begin at 1:40 min and 5:40 min.

Group Type: EXPERIMENTAL

Reduced-exertion high-intensity interval training (REHIT)

Intervention Type: BEHAVIORAL

Description same as Arm description.

Interventions

Reduced-exertion high-intensity interval training (REHIT)

Description same as Arm description.

Intervention Type: BEHAVIORAL

Other Intervention Names

Sprint interval training (SIT)

Eligibility Criteria

Inclusion Criteria

• Male
• Age ≥ 18 y or <40 y
• BMI < 35 kg/m2
• otherwise healthy, untrained individuals

Exclusion Criteria

• Age <18 y or >40 y
• BMI > 35 kg/m2
• classification of 'highly physically active' according to the International Physical Activity Questionnaire (IPAQ)
• answering 'yes' to one or more questions on a standard Physical Activity Readiness Questionnaire (PAR-Q)
• resting heart rate ≥100bpm, clinically significant hypertension (140/90 mmHg)
• a personal history of metabolic or cardiovascular disease
• Female participants because of unknown effects of the menstrual cycle on the levels of the measured myokines.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Stirling

OTHER

Sponsor Role: lead

Responsible Party

Niels Vollaard

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Niels Vollaard, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Stirling

Locations

University of Stirling

Stirling, , United Kingdom

Countries

United Kingdom

Other Identifiers

UStirling

Identifier Type: -

Identifier Source: org_study_id