Chronic Widespread PainEPISIPNCT06475859
The Role of Epigenetic Mechanisms in Stress Intolerance in Patients With Chronic Widespread Pain
An observational study of Chronic Widespread Pain, run by Vrije Universiteit Brussel at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Chronic Widespread Pain
- What is being tested?
- Montreal Imaging Stress Test and Relaxation breathing
- How many people
- 84 participants
- Where
- 1 siteBelgium
- Study dates
- 19 Apr 2023to 18 Apr 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Potential study participants will be recruited mainly through online advertisements, but also in hospitals.
Who may be able to join
- female
- age between 18 and 70 years old
- body mass index (BMI) below 30
- inactive lifestyle
- for patients only: received the diagnosis of fibromyalgia
Who cannot join
- other neurological, endocrine, cardiac, or systemic syndromes
- history of cancer or heart failure
- women that are pregnant or within one year after pregnancy
Trial locations and contacts
1 site in 1 country.
Belgium1 site
Vrije Universiteit Brussel - UZ Brussel
Brussels, Brussels Capital, 1050
About this study
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.
Read the 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.
- Conditions
- Chronic Widespread Pain
- Being tested
- Montreal Imaging Stress Test, Relaxation breathing
- Keywords
- Chronic Widespread Pain, Epigenetics, Autonomic Nervous System, Stress Intolerance
- Medical subject headings
- Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Montreal Imaging Stress TestOther
A mental stress test that induces stress via a series of arithmetic tasks participants need to solve in a few seconds.
Relaxation breathingOther
3 short sessions (4 minutes) of relaxation breathing
| Study group | Role | What they receive |
|---|---|---|
| Women with chronic widespread pain | Women who received the diagnosis of fibromyalgia from a doctor. Receives: Other: Montreal Imaging Stress Test; Other: Relaxation breathing | |
| Healthy women | Healthy women without any chronic diseases or pain in daily life. Receives: Other: Montreal Imaging Stress Test; Other: Relaxation breathing |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA methylation of catecholamine-degrading enzymes
DNA methylation status of catechol-O-methyltransferase (COMT), monoamine oxidase (MAO)-A and MAO-B
Measured: At baseline (i.e. before the mental stress test or relaxation breathing), and 20 minutes after the mental stress test and relaxation breathing
Secondary outcomes (6)
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
Measured: At baseline
Catecholamine levels
Levels of adrenaline, noradrenaline and dopamine in plasma
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2024
- Study start19 Apr 2023
- Primary completion18 Apr 2025
- Study completion18 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Widespread PainStudies of the same condition, open and under way.
- More trials run by Vrije Universiteit BrusselThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vrije Universiteit Brussel
- Sponsor type
- University, hospital or other
- Collaborators
- Research Foundation Flanders, KU Leuven
- Responsible party
- Principal investigator, Jo Nijs, Vrije Universiteit Brussel
- Investigators
- Jo Nijs, PhD, Principal investigator, Vrije Universiteit Brussel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06475859
- Sponsor's protocol ID
- EC-2022-118
- Acronym
- EPISIP
- Status last verified
- Sep 2025
- First submitted
- 16 May 2024
- Last updated
- 19 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Epigenetic Mechanisms in Stress Intolerance in Patients With Chronic Widespread Pain
- ClinicalTrials.gov ID
- NCT06475859
- Acronym / sponsor ID
- EPISIP / EC-2022-118
- Conditions
- Chronic Widespread Pain
- Keywords
- Chronic Widespread Pain, Epigenetics, Autonomic Nervous System, Stress Intolerance
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Vrije Universiteit BrusselUniversity, hospital or other
- Collaborators
- Research Foundation Flanders, KU Leuven
- Study start
- 19 Apr 2023 (actual)
- Primary completion
- 18 Apr 2025 (actual)
- Study completion
- 18 Apr 2025 (actual)
- First posted
- 26 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Women with chronic widespread pain | – | Other: Montreal Imaging Stress Test, Other: Relaxation breathingWomen who received the diagnosis of fibromyalgia from a doctor. |
| Healthy women | – | Other: Montreal Imaging Stress Test, Other: Relaxation breathingHealthy women without any chronic diseases or pain in daily life. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Potential study participants will be recruited mainly through online advertisements, but also in hospitals.
Key inclusion criteria (5 listed)
- female
- age between 18 and 70 years old
- body mass index (BMI) below 30
- inactive lifestyle
- for patients only: received the diagnosis of fibromyalgia
Key exclusion criteria (3 listed)
- other neurological, endocrine, cardiac, or systemic syndromes
- history of cancer or heart failure
- women that are pregnant or within one year after pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Montreal Imaging Stress TestA mental stress test that induces stress via a series of arithmetic tasks participants need to solve in a few seconds. | Other | Healthy women, Women with chronic widespread pain |
| Relaxation breathing3 short sessions (4 minutes) of relaxation breathing | Other | Healthy women, Women with chronic widespread pain |
Primary outcome
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
6 secondary outcomes
Genetic variations in catecholamine-degrading enzymes
Time frame: At baseline
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
Heart rate variability
Time frame: Continuously starting 10 minutes before until 10 minutes after the mental stress test and relaxation breathing
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jo Nijs, PhD principal investigator
Vrije Universiteit Brussel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Widespread Pain, run by Vrije Universiteit Brussel at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2025.