Effects of Genetic Variation on the Efficacy of Aerobic Exercise

Quality of Life Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03670186
• Other study ID #: BDNF V66M Exercise Study
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2018
• Est. completion date: March 1, 2019

Study information

• Verified date: September 2018
• Source: McMaster University
• Contact: Aimee Nelson, PhD
• Phone: 9055259140
• Email: nelsonaj[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 34
• Est. completion date: March 1, 2019
• Est. primary completion date: January 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 30 Years

Eligibility

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.

Related Conditions & MeSH terms

• Quality of Life

Intervention

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.

Locations

Country	Name	City	State
Canada	McMaster University, Ivor Wynne Centre (IWC) building	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
McMaster University

Country where clinical trial is conducted

Canada, 

References & Publications (19)

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Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003 Jan 24;112(2):257-69. — View Citation

Heisz JJ, Clark IB, Bonin K, Paolucci EM, Michalski B, Becker S, Fahnestock M. The Effects of Physical Exercise and Cognitive Training on Memory and Neurotrophic Factors. J Cogn Neurosci. 2017 Nov;29(11):1895-1907. doi: 10.1162/jocn_a_01164. Epub 2017 Jul 12. — View Citation

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Little JP, Gillen JB, Percival ME, Safdar A, Tarnopolsky MA, Punthakee Z, Jung ME, Gibala MJ. Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. J Appl Physiol (1985). 2011 Dec;111(6):1554-60. doi: 10.1152/japplphysiol.00921.2011. Epub 2011 Aug 25. — View Citation

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Lu B, Chow A. Neurotrophins and hippocampal synaptic transmission and plasticity. J Neurosci Res. 1999 Oct 1;58(1):76-87. Review. — View Citation

Lulic T, El-Sayes J, Fassett HJ, Nelson AJ. Physical activity levels determine exercise-induced changes in brain excitability. PLoS One. 2017 Mar 9;12(3):e0173672. doi: 10.1371/journal.pone.0173672. eCollection 2017. — View Citation

Neeper SA, Gómez-Pinilla F, Choi J, Cotman C. Exercise and brain neurotrophins. Nature. 1995 Jan 12;373(6510):109. — View Citation

Ozan E, Okur H, Eker C, Eker OD, Gönül AS, Akarsu N. The effect of depression, BDNF gene val66met polymorphism and gender on serum BDNF levels. Brain Res Bull. 2010 Jan 15;81(1):61-5. doi: 10.1016/j.brainresbull.2009.06.022. — View Citation

Phillips BE, Kelly BM, Lilja M, Ponce-González JG, Brogan RJ, Morris DL, Gustafsson T, Kraus WE, Atherton PJ, Vollaard NBJ, Rooyackers O, Timmons JA. A Practical and Time-Efficient High-Intensity Interval Training Program Modifies Cardio-Metabolic Risk Factors in Adults with Risk Factors for Type II Diabetes. Front Endocrinol (Lausanne). 2017 Sep 8;8:229. doi: 10.3389/fendo.2017.00229. eCollection 2017. — View Citation

Rovio S, Kåreholt I, Helkala EL, Viitanen M, Winblad B, Tuomilehto J, Soininen H, Nissinen A, Kivipelto M. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease. Lancet Neurol. 2005 Nov;4(11):705-11. — View Citation

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Teri L, Gibbons LE, McCurry SM, Logsdon RG, Buchner DM, Barlow WE, Kukull WA, LaCroix AZ, McCormick W, Larson EB. Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. JAMA. 2003 Oct 15;290(15):2015-22. — View Citation

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* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Corticospinal excitability	Corticospinal excitability as measured by single-pulse TMS-evoked responses in a hand and forearm muscles.	8 weeks
Primary	Intracortical circuits	Intracortical circuits as measured by paired-pulse TMS-evoked responses in a hand muscle	8 weeks
Primary	Spinal circuits	Spinal circuits as measured by spinal Hoffman reflexes from a forearm muscle	8 weeks
Primary	Blood BDNF	Serum levels of BDNF as assessed by ELISA	8 weeks
Secondary	Cathepsin B	Serum levels of cathepsin B as assessed by ELISA	8 weeks
Secondary	IGF-1	Serum levels of IGF-1 as assessed by ELISA	8 weeks
Secondary	VEGF	Serum levels of VEGF as assessed by ELISA	8 weeks
Secondary	Osteocalcin	Serum levels of osteocalcin as assessed by ELISA	8 weeks
Secondary	Working memory	Working memory as assessed by the Automated Operation Span (OSPAN) Task	8 weeks
Secondary	Cardiorespiratory fitness	Cardiorespiratory fitness as assessed by VO2 peak test	8 weeks