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

Recruiting
Conditions
Chronic Widespread Pain
Interventions
Other: Montreal Imaging Stress Test
Other: Relaxation breathing
Registration Number
NCT06475859
Lead Sponsor
Vrije Universiteit Brussel
Brief 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.

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
88
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Healthy womenMontreal Imaging Stress TestHealthy women without any chronic diseases or pain in daily life.
Women with chronic widespread painMontreal Imaging Stress TestWomen who received the diagnosis of fibromyalgia from a doctor.
Women with chronic widespread painRelaxation breathingWomen who received the diagnosis of fibromyalgia from a doctor.
Healthy womenRelaxation breathingHealthy women without any chronic diseases or pain in daily life.
Primary Outcome Measures
NameTimeMethod
DNA methylation of catecholamine-degrading enzymesAt 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 Outcome Measures
NameTimeMethod
Heart rate variabilityContinuously starting 10 minutes before until 10 minutes after the mental stress test and relaxation breathing

Heart rate variability measured continuously using the Polar H10

Catecholamine levelsAt 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

Blood pressureAt 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

Genetic variations in catecholamine-degrading enzymesAt 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

Activity of catecholamine-degrading enzymesAt 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

Symptom severityAt 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

Trial Locations

Locations (1)

Vrije Universiteit Brussel - UZ Brussel

🇧🇪

Brussels, Belgium

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