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Completed

NCT Number: NCT03670186

Effects of Genetic Variation on the Efficacy of Aerobic Exercise

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.

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Key information

Conditions

Age range

18 year–30 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

McMaster University, Ivor Wynne Centre (IWC) building

Hamilton, Ontario, L8S4K1, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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;
  • 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;
  • 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;
  • must be right-handed as per the handedness questionnaire;
  • must be between 18 and 30 years old.

Exclusion criteria

  • 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;
  • are not able to engage in physical activity and thus answer 'YES' to any of the GAQ questions;
  • 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;
  • are not right-handed as per the handedness questionnaire;
  • are younger than 18 years of age and older than 30 years of age.

Treatment and study plan

High-Intensity Interval Training (HIIT)

Behavioral

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.

Primary outcomes

  1. Corticospinal excitability

    Time frame: 8 weeks

    Corticospinal excitability as measured by single-pulse TMS-evoked responses in a hand and forearm muscles.

  2. Intracortical circuits

    Time frame: 8 weeks

    Intracortical circuits as measured by paired-pulse TMS-evoked responses in a hand muscle

  3. Spinal circuits

    Time frame: 8 weeks

    Spinal circuits as measured by spinal Hoffman reflexes from a forearm muscle

  4. Blood BDNF

    Time frame: 8 weeks

    Serum levels of BDNF as assessed by ELISA

Secondary outcomes

  1. Cathepsin B

    Time frame: 8 weeks

    Serum levels of cathepsin B as assessed by ELISA

  2. IGF-1

    Time frame: 8 weeks

    Serum levels of IGF-1 as assessed by ELISA

  3. VEGF

    Time frame: 8 weeks

    Serum levels of VEGF as assessed by ELISA

  4. Osteocalcin

    Time frame: 8 weeks

    Serum levels of osteocalcin as assessed by ELISA

  5. Working memory

    Time frame: 8 weeks

    Working memory as assessed by the Automated Operation Span (OSPAN) Task

  6. Cardiorespiratory fitness

    Time frame: 8 weeks

    Cardiorespiratory fitness as assessed by VO2 peak test

Sponsors and collaborators

Lead sponsor

McMaster University

Other

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2018
Study completion
2019
First posted
Sep 13, 2018
Registry last updated
Nov 20, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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