Epigenetics of Post-exertional Malaise in Patients With ME/CFS

NCT04378634 | Completed

• 1 other identifier: EPIME
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

Exploring epigenetic mechanisms of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is crucial to understand the mechanisms underlying its pathophysiology. Three potential candidates have been selected (BDNF, COMT, and HDAC genes). DNA methylation in the promoter regions of those genes will be explored. The investigators designed a randomised controlled trial and will enrol 70 patients with ME/CFS and 35 age-, sex-, and BMI-matched healthy controls. Both groups will be randomised in 2 groups and receive either one session of aerobic exercise or a validated test designed to trigger mental stress and mental fatigue. The primary aim is to assess genetic and epigenetic mechanisms of BDNF, COMT and HDAC genes in response to exercise and the stress task.

Conditions

Fatigue Syndrome, Chronic

Keywords

Chronic Fatigue Syndrome; Exercise; Epigenetics; DNA methylation

Outcome Measures

Primary Outcomes (1)

• DNA methylation

  DNA methylation measured at several CpGs of the genes' promoter regions using pyrosequencing technology

  Baseline through 1 week post intervention

Secondary Outcomes (4)

• Clinical Symptoms

  Baseline through 1 week post intervention

• Pain sensitivity

  Baseline through 1 week post intervention

• Serum BDNF

  Baseline through 1 week post intervention

• Cortisol response

  Baseline through 1 week post intervention

Other Outcomes (2)

• General Health

  Baseline

• Gene's polymorphisms

  Baseline

Study Arms (4)

ME/CFS Exercise

EXPERIMENTAL

Patients undergoing the physical stress test (aerobic power index)

Behavioral: Exercise; Other: Mental Stress Test

Patients Stress

EXPERIMENTAL

Patients undergoing the mental stress task (MIST)

Behavioral: Exercise; Other: Mental Stress Test

Healthy Exercise

ACTIVE COMPARATOR

Healthy controls undergoing the physical stress test (aerobic power index)

Behavioral: Exercise; Other: Mental Stress Test

Healthy Stress

ACTIVE COMPARATOR

Healthy controls undergoing the mental stress task (MIST)

Behavioral: Exercise; Other: Mental Stress Test

Interventions

Exercise BEHAVIORAL

Sub-maximal exercise test

Also known as: Aerobic Power Index

Healthy Exercise; Healthy Stress; ME/CFS Exercise; Patients Stress

Mental Stress Test OTHER

Computerised mental arithmetic challenges and social evaluative threat tasks

Also known as: Montreal Imaging Stress Task

Healthy Exercise; Healthy Stress; ME/CFS Exercise; Patients Stress

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosis of ME/CFS established by a MD experienced in the field of internal medicine and ME/CFS - according to the published international criteria developed by the Canadian Consensus Criteria (CCC);
• age between 18 and 70 years old;
• body mass index (BMI) below 30 (no obesity).

You may not qualify if:

• presence of other neurological disorders (Parkinson's disease, Multiple Sclerosis, etc);
• presence of systemic disorders (lupus erythematosus, rheumatoid arthritis, etc.);
• presence or history of cardiac disorders (coronary heart disease, history of heart failure, etc);
• presence or history of cancer;
• presence or history of neuropathic pain (e.g. pain related to herpes zoster virus);
• pregnancy;

Sponsors & Collaborators

• Vrije Universiteit Brussel: lead

Study Sites (1)

UZ Brussel

Brussels, 1090, Belgium

Location

Related Publications (3)

• de Vega WC, Vernon SD, McGowan PO. DNA methylation modifications associated with chronic fatigue syndrome. PLoS One. 2014 Aug 11;9(8):e104757. doi: 10.1371/journal.pone.0104757. eCollection 2014.

  PMID: 25111603 BACKGROUND

• Vangeel EB, Kempke S, Bakusic J, Godderis L, Luyten P, Van Heddegem L, Compernolle V, Persoons P, Lambrechts D, Izzi B, Freson K, Claes S. Glucocorticoid receptor DNA methylation and childhood trauma in chronic fatigue syndrome patients. J Psychosom Res. 2018 Jan;104:55-60. doi: 10.1016/j.jpsychores.2017.11.011. Epub 2017 Nov 20.

  PMID: 29275786 BACKGROUND

• Trivedi MS, Oltra E, Sarria L, Rose N, Beljanski V, Fletcher MA, Klimas NG, Nathanson L. Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns. PLoS One. 2018 Jul 23;13(7):e0201066. doi: 10.1371/journal.pone.0201066. eCollection 2018.

  PMID: 30036399 BACKGROUND

MeSH Terms

Conditions

Fatigue Syndrome, Chronic; Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Jo Nijs, PhD

  Vrije Universiteit Brussel

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, principal investigator

Model Details: Randomised Controlled Trial

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: May 7, 2020
• Study Start: April 1, 2021
• Primary Completion: April 30, 2023
• Study Completion: April 30, 2023
• Last Updated: November 7, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)