Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of Genetic Variation on the Efficacy of Aerobic Exercise

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03670186
Recruitment Status : Recruiting
First Posted : September 13, 2018
Last Update Posted : September 13, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Quality of Life Behavioral: High-Intensity Interval Training (HIIT) Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effects of BDNF Val66Met Polymorphism on the Efficacy of Aerobic Exercise in Sedentary, Healthy Males
Actual Study Start Date : February 1, 2018
Estimated Primary Completion Date : January 1, 2019
Estimated Study Completion Date : March 1, 2019

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  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 Outcome Measures :
  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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 30 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03670186


Contacts
Layout table for location contacts
Contact: Aimee Nelson, PhD 9055259140 ext 28053 nelsonaj@mcmaster.ca
Contact: Chiara Nicolini, PhD nicolc@mcmaster.ca

Locations
Layout table for location information
Canada, Ontario
McMaster University, Ivor Wynne Centre (IWC) building Recruiting
Hamilton, Ontario, Canada, L8S4K1
Contact: Aimee Nelson, PhD    9055259140 ext 28053    nelsonaj@mcmaster.ca   
Sponsors and Collaborators
McMaster University
Investigators
Layout table for investigator information
Principal Investigator: Aimee Nelson, PhD McMaster University
Publications:

Layout table for additonal information
Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT03670186    
Other Study ID Numbers: BDNF V66M Exercise Study
First Posted: September 13, 2018    Key Record Dates
Last Update Posted: September 13, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No