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Completed

NCT Number: NCT06475859

The Role of Epigenetic Mechanisms in Stress Intolerance in Patients With Chronic Widespread Pain

Patients with chronic widespread pain (CWP) frequently experience stress intolerance - an exacerbation of symptoms in response to stress. Although it severely affects their quality of life, stress intolerance remains a mystery. Hence, unravelling the mechanisms underlying stress intolerance is crucial to understand CWP pathophysiology and to develop novel treatments. Epigenetic mechanisms hold the potential to provide an answer as they have been found to be altered in patients with CWP at baseline, and in response to stress. However, research on epigenetic mechanisms in CWP is very scarce. Hence, this study aims to address this knowledge gap by assessing stress-induced epigenetic changes in patients with CWP and healthy controls aiming to unravel whether epigenetic mechanisms can help explain stress intolerance. The regulatory role of epigenetic mechanisms will be researched in relation to the activity of enzymes affected by the epigenetic mechanisms, neurophysiological measures, and stress-induced symptom changes in patients with CWP.

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Key information

Conditions

Chronic Widespread Pain Chronic Pain Neurologic Manifestations Pain Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–70 year

Sex eligibility

Female

Study type

Observational

Primary location

Vrije Universiteit Brussel - UZ Brussel

Brussels, Brussels Capital, 1050, Belgium

About this study

The objectives of this project will be tackled by a randomized cross-over study including 44 patients with CWP and 44 healthy controls. Participants are expected to come to the hospital twice and fill in questionnaires at several defined timepoints. Two days before their first visit, participants will complete baseline questionnaires at home via REDCap, which will take approximately one hour. Next, participants will be randomised into Group 1 (undergoing the mental stress test at their first visit and then relaxation breathing) or Group 2 (undergoing relaxation breathing at their first visit and then the mental stress test). During each hospital visit, the participants will be assessed before, during and after the intervention. The Pre-test assessment consists of a blood withdrawal, five short questionnaires, examination of pain thresholds, and neurophysiological measurements. The latter will continue during the intervention, which consists of a mental stress test or relaxation breathing. The Post-test assessment consists of a blood withdrawal, one short questionnaire, examination of pain thresholds, and neurophysiological measurements. Then there are again 2 home-based assessments via REDCap 24h and 7 days after the intervention during which the participants will in 1 or 5 short questionnaires, respectively.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • female
  • age between 18 and 70 years old
  • body mass index (BMI) below 30
  • inactive lifestyle
  • for patients only: received the diagnosis of fibromyalgia

Exclusion criteria

  • other neurological, endocrine, cardiac, or systemic syndromes
  • history of cancer or heart failure
  • women that are pregnant or within one year after pregnancy

Treatment and study plan

Montreal Imaging Stress Test

Other

A mental stress test that induces stress via a series of arithmetic tasks participants need to solve in a few seconds.

Relaxation breathing

Other

3 short sessions (4 minutes) of relaxation breathing

Primary outcomes

  1. DNA methylation of catecholamine-degrading enzymes

    Time frame: At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing

    DNA methylation status of catechol-O-methyltransferase (COMT), monoamine oxidase (MAO)-A and MAO-B

Secondary outcomes

  1. Genetic variations in catecholamine-degrading enzymes

    Time frame: At baseline

    COMT: rs4818; rs4680 MAO-A: rs6323; MAOA-uVNTR MAO-B: rs1799836 COMT: rs4818; rs4680 MAO-A: rs6323; MAOA-uVNTR MAO-B: rs1799836 COMT: rs4818; rs4680 MAO-A: rs6323; MAOA-uVNTR MAO-B: rs1799836 COMT: rs4818; rs4680; MAO-A: rs6323; MAOA-uVNTR; MAO-B: rs1799836

  2. Catecholamine levels

    Time frame: At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing

    Levels of adrenaline, noradrenaline and dopamine in plasma

  3. Heart rate variability

    Time frame: Continuously starting 10 minutes before until 10 minutes after the mental stress test and relaxation breathing

    Heart rate variability measured continuously using the Polar H10

  4. Blood pressure

    Time frame: At baseline (i.e. before the mental stress test or relaxation breathing), during (3 times with 4 minutes in between) and 10 minutes after the mental stress test and relaxation breathing

    Blood pressure, both systolic and diastolic, measured at specified moments using a digital device

  5. Activity of catecholamine-degrading enzymes

    Time frame: At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing

    Activity of the enzymes will be defined in plasma or PBMCs

  6. Symptom severity

    Time frame: At baseline (i.e. before the mental stress test or relaxation breathing), and 10 minutes, 24 hours and 7 days after the mental stress test and relaxation breathing

    Symptom severity which is assessed through the Chronic Fatigue Syndrome Symptom List

Other outcomes

  1. Temperature and pressure pain thresholds

    Time frame: At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing

    Pain thresholds for warmth and cold measured with the TSA-II, and pressure measured with a digital algometer on the hand and leg. Pain intensity is reported through a numeric rating scale ranging from 0 (no pain) to 10 (worst pain).

  2. Level of stress

    Time frame: At baseline (i.e. before the mental stress test or relaxation breathing), during (3 times with 4 minutes in between) and 10 minutes, 24 hours and 7 days after the mental stress test and relaxation breathing

    Numeric rating scale ranging from 0 (no stress) to 10 (worst stress) indicating the level of stress

Sponsors and collaborators

Lead sponsor

Vrije Universiteit Brussel

Other

Collaborators

  • KU Leuven
  • Research Foundation Flanders

Registry information

Acronym: EPISIP

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Jun 26, 2024
Registry last updated
Sep 19, 2025

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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