Effects of Genetic Variation on the Efficacy of Aerobic Exercise

November 19, 2024 updated by: McMaster University

Effects of BDNF Val66Met Polymorphism on the Efficacy of Aerobic Exercise in Sedentary, Healthy Males

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8S4K1
        • McMaster University, Ivor Wynne Centre (IWC) building

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 26 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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.

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: V66V-HIIT
Val/Val carriers who undergo high-intensity interval training (HIIT) for 6 weeks, 3 times per week
Behavioral: High-Intensity Interval Training (HIIT)
Participants perform high-intensity interval training (HIIT) on a cycle ergometer. The HIIT protocol consists of a 3-minute warm-up at 50W, ten 60-second high-intensity cycling intervals interspersed with 90 seconds of active recovery at 30% of their peak power output and a 2-minute cool-down at 50W for a total of 17.5 minutes.
Experimental: V66M-HIIT
Val/Met carriers who undergo high-intensity interval training (HIIT) for 6 weeks, 3 times per week
Behavioral: High-Intensity Interval Training (HIIT)
Participants perform high-intensity interval training (HIIT) on a cycle ergometer. The HIIT protocol consists of a 3-minute warm-up at 50W, ten 60-second high-intensity cycling intervals interspersed with 90 seconds of active recovery at 30% of their peak power output and a 2-minute cool-down at 50W for a total of 17.5 minutes.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

McMaster University

Investigators

  • Principal Investigator: Aimee Nelson, PhD, McMaster University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2018

Primary Completion (Actual)

December 3, 2018

Study Completion (Actual)

January 21, 2019

Study Registration Dates

First Submitted

September 5, 2018

First Submitted That Met QC Criteria

September 11, 2018

First Posted (Actual)

September 13, 2018

Study Record Updates

Last Update Posted (Actual)

November 20, 2024

Last Update Submitted That Met QC Criteria

November 19, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • BDNF V66M Exercise Study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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