The Role of Epigenetic Mechanisms in Stress Intolerance in Patients With Chronic Widespread Pain
NCT Number: NCT06475859
Acronym: EPISIP
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: Chronic Widespread Pain
Interventions: OTHER: Montreal Imaging Stress Test|OTHER: Relaxation breathing
Sponsor: Vrije Universiteit Brussel
Collaborators: Research Foundation Flanders|KU Leuven
Sex: FEMALE
Age: ADULT, OLDER_ADULT
Enrollment: 88
Study Design: Observational Model: |Time Perspective: p
Start Date: 2023-04-19
Completion Date: 2024-12-31
Locations: Vrije Universiteit Brussel - UZ Brussel, Brussels, 1050, Belgium

Summary:
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.

Primary Outcome Measures: DNA methylation of catecholamine-degrading enzymes, DNA methylation status of catechol-O-methyltransferase (COMT), monoamine oxidase (MAO)-A and MAO-B, At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing
Secondary Outcome Measures: Genetic variations in catecholamine-degrading enzymes, 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, At baseline|Catecholamine levels, Levels of adrenaline, noradrenaline and dopamine in plasma, At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing|Heart rate variability, Heart rate variability measured continuously using the Polar H10, Continuously starting 10 minutes before until 10 minutes after the mental stress test and relaxation breathing|Blood pressure, Blood pressure, both systolic and diastolic, measured at specified moments using a digital device, 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|Activity of catecholamine-degrading enzymes, Activity of the enzymes will be defined in plasma or PBMCs, At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing|Symptom severity, Symptom severity which is assessed through the Chronic Fatigue Syndrome Symptom List, 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
Other Outcome Measures: Temperature and pressure pain thresholds, 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)., At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing|Level of stress, Numeric rating scale ranging from 0 (no stress) to 10 (worst stress) indicating the level of stress, 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