Effects of Genetic Variation on the Efficacy of Aerobic Exercise

Not Applicable

Completed

• Conditions: Quality of Life
• Interventions: Behavioral: High-Intensity Interval Training (HIIT)

• Registration Number: NCT03670186
• Lead Sponsor: McMaster University

Brief Summary

This study investigates whether, after six weeks of exercise, a genetic variant (Val66Met) in the gene that makes a molecule (BDNF) important for brain health and function, influences the beneficial effects of a further session of exercise in sedentary, healthy males. The aim of this research is to determine whether not having this genetic variant (Val66Met) provides an advantage for achieving greater exercise-induced benefits. After six consecutive weeks of exercise (high-intensity interval training (HIIT), three times per week), the effects of a further session of exercise on brain activity are studied in healthy, sedentary males with and without the BDNF genetic variant. Further, whether the BDNF genetic variant impacts the effects of six weeks of aerobic exercise on blood BDNF levels, memory and cardiorespiratory fitness is examined. This data will help to understand whether genetic factors moderate the beneficial effects of exercise. Understanding what factors influence the effectiveness of exercise training programs is essential to individualize exercise programs and maximize their positive effects on the brain and during rehabilitation following brain injuries.

Detailed Description

Aerobic exercise promotes brain health and function. Indeed, exercise has been shown to improve learning and memory, delay cognitive decline and protect against brain atrophy in healthy aging individuals. Additionally, exercise programs reduce brain injury and delay onset and progression of neurodegenerative diseases such as Alzheimer's. However, individual variability in the efficacy of these programs limit their widespread application as a "therapeutic". Genetic variants may contribute to the large degree of individual variability in the effects of exercise on cognition and brain health.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in activity-dependent neuroplasticity. Rodent studies show that increases in BDNF mediate the effects of exercise on learning and memory. A single nucleotide polymorphism in the BDNF gene that causes a valine (Val) to methionine (Met) substitution at codon 66 reduces activity-dependent secretion of BDNF and is associated with altered hippocampal activation and poorer episodic memory. The objective of this research is to determine whether after six consecutive weeks of high-intensity interval training (HIIT), three times per week, BDNF Val66Met polymorphism impacts the effects of a further HIIT session on corticospinal excitability as well as intracortical and spinal circuitry. Additionally, this study aims to assess whether BDNF Val66Met polymorphism moderates the effects of six consecutive weeks of HIIT on BDNF, working memory and cardiorespiratory fitness levels. The findings will indicate whether the BDNF Val allele provides an advantage for achieving greater exercise-induced benefits and could thus help individualize exercise programs to maximize their beneficial effects. These data will also provide insights into the mechanisms by which aerobic exercise induces neuroplasticity.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2018-02-01
• Study First Submitted: 2018-09-05
• Study First Submitted QC: 2018-09-11
• Study First Posted: 2018-09-13
• Primary Completion: 2018-12-03
• Study Completion: 2019-01-21
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-19
• Last Update Posted: 2024-11-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 18

Inclusion Criteria

1. do not engage or engage in less than or equal to 60 minutes of structured exercise per week (or two exercise sessions of 30 min/week; Heisz et al., 2017; Little et al. 2011) as per their self-report;
2. must be able to engage in physical activity and thus must answer 'NO' to all questions on the Get Active Questionnaire (GAQ). If potential participants answer 'YES' to any of the GAQ questions, they are immediately deemed ineligible to partake in the research;
3. must not take street drugs and medications, including alpha blockers, antibiotics, antipsychotics, benzodiazepines, beta-blockers, calcium channel blockers, systemic corticosteroids, muscle relaxants, neuromuscular blocking agents, sedatives, and psychostimulants, and must have no stable or unstable medical conditions, history of neurological or psychological disorders, head injury and/or surgery, seizures or have a family history of seizures or epilepsy, experience frequent headaches, migraines and sleep deprivation as per the TMS screening form;
4. must be right-handed as per the handedness questionnaire;
5. must be between 18 and 30 years old.

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Exclusion Criteria

1. engage in more than 60 minutes of structured exercise per week (or two exercise sessions of 30 min/week; Heisz et al., 2017; Little et al. 2011) as per their self-report;
2. are not able to engage in physical activity and thus answer 'YES' to any of the GAQ questions;
3. take street drugs and medications, including alpha blockers, antibiotics, antipsychotics, benzodiazepines, beta-blockers, calcium channel blockers, systemic corticosteroids, muscle relaxants, neuromuscular blocking agents, sedatives, and psychostimulants, and must have no stable or unstable medical conditions, history of neurological or psychological disorders, head injury and/or surgery, seizures or have a family history of seizures or epilepsy, experience frequent headaches, migraines and sleep deprivation as per the TMS screening form;
4. are not right-handed as per the handedness questionnaire;
5. are younger than 18 years of age and older than 30 years of age.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
V66V-HIIT	High-Intensity Interval Training (HIIT)	Val/Val carriers who undergo high-intensity interval training (HIIT) for 6 weeks, 3 times per week
V66M-HIIT	High-Intensity Interval Training (HIIT)	Val/Met carriers who undergo high-intensity interval training (HIIT) for 6 weeks, 3 times per week

Primary Outcome Measures

Name	Time	Method
Spinal circuits	8 weeks	Spinal circuits as measured by spinal Hoffman reflexes from a forearm muscle
Corticospinal excitability	8 weeks	Corticospinal excitability as measured by single-pulse TMS-evoked responses in a hand and forearm muscles.
Intracortical circuits	8 weeks	Intracortical circuits as measured by paired-pulse TMS-evoked responses in a hand muscle
Blood BDNF	8 weeks	Serum levels of BDNF as assessed by ELISA

Secondary Outcome Measures

Name	Time	Method
Cathepsin B	8 weeks	Serum levels of cathepsin B as assessed by ELISA
Osteocalcin	8 weeks	Serum levels of osteocalcin as assessed by ELISA
Working memory	8 weeks	Working memory as assessed by the Automated Operation Span (OSPAN) Task
VEGF	8 weeks	Serum levels of VEGF as assessed by ELISA
IGF-1	8 weeks	Serum levels of IGF-1 as assessed by ELISA
Cardiorespiratory fitness	8 weeks	Cardiorespiratory fitness as assessed by VO2 peak test

Trial Locations

Locations (1)

McMaster University, Ivor Wynne Centre (IWC) building; 🇨🇦 Hamilton, Ontario, Canada