EndometriosisPEARLNCT06332560
Pain in Endometriosis And the Relation to Lifestyle
A study testing Anti-inflammatory diet (DI) and Cognitive behavioral therapy (CBT) in people with Endometriosis and Adenomyosis, run by Radboud University Medical Center at 5 sites in Netherlands.
Trial summary
The goal of this clinical trial is to investigate the effect of an anti-inflammatory diet and cognitive behavioral therapy (CBT) on pain symptoms, health related quality of life and the effect on inflammatory characteristics in serum and menstruum samples as well as the effect on the gut and vaginal microbiome in… Read more about this study
- Who is it for?
- Ages 17 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Endometriosis, Adenomyosis
- What is being tested?
- Anti-inflammatory diet (DI) and Cognitive behavioral therapy (CBT)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 5 sitesNetherlands
- Study dates
- 4 Oct 2024to May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 17 years and older
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Confirmed diagnosis of endometriosis via ultrasound, MRI or surgery*
- NRS pain score > 4*
- Age from 17 years
- Premenopausal status
- Body Mass Index (BMI) 18-30 kg/m2
- Ability to understand the explanation about the diet intervention (DI) and CBT*
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- Willing to follow the DI*
- Willing to continue their use of food supplements
- Willing to undergo CBT*
- Willing to collect menstrual effluent, and therefore willing to have two stop weeks from hormonal contraception (if applicable) during the study period.
Who cannot join
- Recurrent miscarriages (> 2)
- Eating disorder
- Diagnosed with Crohn's disease, Ulcerative Colitis, short bowel syndrome or another chronic inflammatory disease
- Self-reported celiac disease
- Vegan diet
- Smoking
Show all 17Show fewer
- Use of immunosuppressive or psychotropic medication
- Score on FFQ > 120
- Diagnosed with severe mental disorder currently requiring treatment by psychiatrist
- NRS average score below 4 during the last month
- Participation in another intervention study
- Unable to speak Dutch or to understand the intervention
- Need for surgery during the participation in the study
- Serious pain (NRS > 4) from other origin than endometriosis
- Pregnant
- Scalp hair shorter than 4 cm
- Only applicable to patients with endometriosis
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Netherlands5 sites, 5 recruiting
- Recruiting
Jeroen Bosch Hospital (JBZ)
's-Hertogenbosch
M.C. Herman, PhD
- Recruiting
Rijnstate Hospital
Arnhem
P Dijkhuizen, PhD
- Recruiting
Amphia
Breda
J.S. Hoogstad-van Evert, PhD
- Recruiting
Catharina Hospital
Eindhoven
H.A.A.M van Vliet, PhD, MD
- Recruiting
Radboud University Medical Center
Nijmegen
E Huijs, B
A.W. Nap, MD PhD
About this study
Official title: Pain in Endometriosis And the Relation to Lifestyle: Effectiveness of a Dietary Intervention and Cognitive Behavioral Therapy in Endometriosis-associated Pain
The goal of this clinical trial is to investigate the effect of an anti-inflammatory diet and cognitive behavioral therapy (CBT) on pain symptoms, health related quality of life and the effect on inflammatory characteristics in serum and menstruum samples as well as the effect on the gut and vaginal microbiome in women with endometriosis. In addition, we want to investigate the differences in stress (measured by hair cortisol levels), inflammatory markers in peripheral blood, menstrual effluent, and the vaginal and intestinal microbiome between persons without and with endometriosis. Participants will be randomized between standard care (control group), standard care and an anti-inflammatory diet intervention, or standard care, an anti-inflammatory diet intervention and CBT or CBT alone. Participants will follow an anti-inflammatory diet based on the Dutch Dietary Guidelines or CBT or a combination of both interventions for 12 weeks. They will receive personalized dietary advice from a dietician and recipes will be available. cognitive behavioral therapy will be administered in a total of seven individual sessions led by a psychotherapist. The content of these sessions will be psycho-education regarding pain mechanisms (and diet).
- Conditions
- Endometriosis, Adenomyosis
- Being tested
- Anti-inflammatory diet (DI), Cognitive behavioral therapy (CBT)
- Keywords
- endometriosis, pain, quality of life, immunology, anti-inflammatory diet, cognitive behavioral therapy, adenomyosis, diet, microbiome
- Medical subject headings
- Endometriosis, Adenomyosis, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-inflammatory diet (DI)Behavioural
Also called DI
12-week personalized dietary advice based on the Dutch Dietary Guidelines under the guidance of a dietician.
Cognitive behavioral therapy (CBT)Behavioural
Also called CBT
Seven individual sessions led by a psychotherapist. The content of the CBT will be psycho-education regarding pain mechanisms and DI.
| Study group | Role | What they receive |
|---|---|---|
| Standard care (control group) | No intervention | Not described |
| Standard care and an anti-inflammatory diet (DI group) | Experimental | Not described Receives: Behavioral: Anti-inflammatory diet (DI) |
| Standard care, anti-inflammatory diet and cognitive behavioral therapy (DI + CBT group) | Experimental | Not described Receives: Behavioral: Anti-inflammatory diet (DI); Behavioral: Cognitive behavioral therapy (CBT) |
| Standard care and cognitive behavioral therapy (CBT group) | Experimental | Not described Receives: Behavioral: Cognitive behavioral therapy (CBT) |
| Healthy controls | No intervention | Healthy controls without endometriosis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pain intensity assessed by the Numerical Rating Scale
The Numerical Rating Scale (NRS) ranges from 0 (no pain) to 10 (unbearable pain), and is the most commonly used subjective measure to assess pain intensity. Patients will score there estimated average pain intensity and there highest pain intensity of the previous 7 days.
Minimum value: 0 Maximum value: 10 Higher score indicates a higher level of pain intensity.
Measured: 3 months
Secondary outcomes (8)
Change in health related quality of life assessed by the Endometriosis Health Profile 30
The Endometriosis Health Profile 30 (EHP-30) is a disease-specific QoL questionnaire which is validated for use in endometriosis patients and measures the impact of the disease on physical, mental and social aspects of life.
The EHP-30 is not a numerical scale.
Measured: 3 months
Change in general quality of llife assessed by the Short Form 36
The Short Form 36 (SF-36) is a multipurpose, general health survey which is applied to measure QoL on nine different domains: physical functioning, social functioning, role limitations due to physical health, role limitations due to emotional problems, emotional well-being, vitality, pain, general health, and health change.
The SF-36 is not a numerical scale.
Measured: 3 months
Change in inflammatory characteristics in menstruum
High-dimensional flow cytometry will be done to analyse immune cells such as T cells, B cells, monocytes, and macrophages. Also Naturel Killer (NK) cells will be analysed. Also in the menstruum, markers for (cluster of differentiation 56) CD56, (cluster of differentiation antigen 16) CD16, (killer immunoglobulin receptors)) KIR and (natural cytotoxicity receptors) NCR, and activation markers such as CD69 will be characterised.
Measured: 3 months
Change in inflammatory charecteristics in peripheral blood
High-dimensional flow cytometry will be done to analyse immune cells such as T cells, B cells, monocytes, and macrophages. Also NK cells will be analysed. Previous studies have described a key role for NK cells in endometriosis. A decreased percentage of NK cells was observed in peritoneal fluid of endometriosis patients compared to HC (Hoogstad-vanEvert et al., 2018 ). For in depth NK cell characterisation we will include markers for CD56, CD16, KIR (killer immunoglobulin receptors) and NCR (natural cytotoxicity receptors), and activation markers such as CD69.
Measured: 3 months
Change in soluble factors in plasma
Analysed with the Olink Proteomics 96 inflammatory panel and Luminex multiplex assay for important soluble factors in endometriosis, i.e. IFNy, TNFα, TNFβ, IL1, IL2, IL6, IL8, IL12 and IL15, VEGF, Granzyme B, and perforin.
Measured: 3 months
Change in the composition of vaginal and intestinal microbiome
Through 16S sRNA gene profiling the microbiome composition of faecal samples and vaginal swabs will be determined. Vaginal and faecal samples will be stored for later microbiome analysis if the the investigators see clear differences in inflammatory profiles after the dietary intervention.
Measured: 3 months
Change in objective stress assessed by measuring scalp hair cortisol levels
Cortisol will be extracted from hair. The researcher will carefully collect a scalp hair sample of at least 0,5 cm thickness and sent these to the laboratory to analyze. The most proximal part represents the most recently grown piece of hair. Hair samples will be cut into a segment corresponding to the 4 cm closest to the scalp, reflecting cortisol secretion over the four months prior to sample collection. Cortisol extraction from hair will be carried out using an enzyme-linked immunoassay (ELISA).
Measured: 3 months
Adherence and anti-inflammatory status of the diet
Diet quality will be assessed by the Eetscore. The Eetscore is a short (Food Frequency Questionnaire) FFQ, developed to assess the Dutch Healthy Diet 2015 (DHD2015) index. The questionnaire is composed of 40 questions assessing the frequency of consumption of food items. From the Eetscore FFQ, a DHD2015-index score can be calculated, indicating the diet quality of an individual.
Ranges from 0 (unhealthy diet) - 160 (healthy diet).
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2024
- Study start4 Oct 2024
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for EndometriosisStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development, Belgian Volition SRL, ASSOCIATION OF PEOPLE WITH ENDOMETRIOSIS I AM 1 IN 10, Wageningen University and Research, Endometriosis UK, University College Cork, SVEUCILISTE U ZAGREBU MEDICINSKI FAKULTET, UNIWERSYTET MEDYCZNY W LUBLINIE, University of Edinburgh, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, Université Catholique de Louvain, University of Bonn, Biopsychology, Horizon Europe
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06332560
- Sponsor's protocol ID
- NL86247.091.24
- Acronym
- PEARL
- Status last verified
- Dec 2024
- First submitted
- 13 Mar 2024
- Last updated
- 11 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Huijs E, van der Sman L, Wirken L, Delcliseur HS, Winter EG, de Roos NM, van der Molen RG, Oosterman JM, Vigano P, Horne AW, Dolmans MM, Hoogstad-van Evert JS, Nap AW; EUmetriosis Working Group. Effectiveness of an anti-inflammatory diet intervention and cognitive behavioural therapy in endometriosis: protocol for a randomised controlled clinical trial. BMJ Open. 2026 May 26;16(5):e116964. doi: 10.1136/bmjopen-2026-116964.
PubMed 42191188
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pain in Endometriosis And the Relation to Lifestyle: Effectiveness of a Dietary Intervention and Cognitive Behavioral Therapy in Endometriosis-associated Pain
- ClinicalTrials.gov ID
- NCT06332560
- Acronym / sponsor ID
- PEARL / NL86247.091.24
- Conditions
- Endometriosis, Adenomyosis
- Keywords
- endometriosis, pain, quality of life, immunology, anti-inflammatory diet, cognitive behavioral therapy, adenomyosis, diet
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development, Belgian Volition SRL, ASSOCIATION OF PEOPLE WITH ENDOMETRIOSIS I AM 1 IN 10, Wageningen University and Research, Endometriosis UK, University College Cork, SVEUCILISTE U ZAGREBU MEDICINSKI FAKULTET, UNIWERSYTET MEDYCZNY W LUBLINIE, University of Edinburgh, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, Université Catholique de Louvain, University of Bonn, Biopsychology, Horizon Europe
- Study start
- 4 Oct 2024 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 27 Mar 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.
The goal of this clinical trial is to investigate the effect of an anti-inflammatory diet and cognitive behavioral therapy (CBT) on pain symptoms, health related quality of life and the effect on inflammatory characteristics in serum and menstruum samples as well as the effect on the gut and vaginal microbiome in women with endometriosis. In addition, we want to investigate the differences in stress (measured by hair cortisol levels), inflammatory markers in peripheral blood, menstrual effluent, and the vaginal and intestinal microbiome between persons without and with endometriosis. Participants will be randomized between standard care (control group), standard care and an anti-inflammatory diet intervention, or standard care, an anti-inflammatory diet intervention and CBT or CBT alone. Participants will follow an anti-inflammatory diet based on the Dutch Dietary Guidelines or CBT or a combination of both interventions for 12 weeks. They will receive personalized dietary advice from a dietician and recipes will be available. cognitive behavioral therapy will be administered in a total of seven individual sessions led by a psychotherapist. The content of these sessions will be psycho-education regarding pain mechanisms (and diet).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Standard care (control group) | No intervention | – |
| Standard care and an anti-inflammatory diet (DI group) | Experimental | Behavioral: Anti-inflammatory diet (DI) |
| Standard care, anti-inflammatory diet and cognitive behavioral therapy (DI + CBT group) | Experimental | Behavioral: Anti-inflammatory diet (DI), Behavioral: Cognitive behavioral therapy (CBT) |
| Standard care and cognitive behavioral therapy (CBT group) | Experimental | Behavioral: Cognitive behavioral therapy (CBT) |
| Healthy controls | No intervention | –Healthy controls without endometriosis |
Who may qualify
- Ages
- 17 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Confirmed diagnosis of endometriosis via ultrasound, MRI or surgery*
- NRS pain score > 4*
- Age from 17 years
- Premenopausal status
- Body Mass Index (BMI) 18-30 kg/m2
Key exclusion criteria (17 listed)
- Recurrent miscarriages (> 2)
- Eating disorder
- Diagnosed with Crohn's disease, Ulcerative Colitis, short bowel syndrome or another chronic inflammatory disease
- Self-reported celiac disease
- Vegan diet
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 |
|---|---|---|
| Anti-inflammatory diet (DI)Also: DI12-week personalized dietary advice based on the Dutch Dietary Guidelines under the guidance of a dietician. | Behavioural | Standard care and an anti-inflammatory diet (DI group), Standard care, anti-inflammatory diet and cognitive behavioral therapy (DI + CBT group) |
| Cognitive behavioral therapy (CBT)Also: CBTSeven individual sessions led by a psychotherapist. The content of the CBT will be psycho-education regarding pain mechanisms and DI. | Behavioural | Standard care and cognitive behavioral therapy (CBT group), Standard care, anti-inflammatory diet and cognitive behavioral therapy (DI + CBT group) |
Primary outcome
Change in Pain intensity assessed by the Numerical Rating Scale
Time frame: 3 months
The Numerical Rating Scale (NRS) ranges from 0 (no pain) to 10 (unbearable pain), and is the most commonly used subjective measure to assess pain intensity. Patients will score there estimated average pain intensity and there highest pain intensity of the previous 7 days. Minimum value: 0 Maximum value: 10 Higher score indicates a higher level of pain intensity.
8 secondary outcomes
Change in health related quality of life assessed by the Endometriosis Health Profile 30
Time frame: 3 months
Change in general quality of llife assessed by the Short Form 36
Time frame: 3 months
Change in inflammatory characteristics in menstruum
Time frame: 3 months
Change in inflammatory charecteristics in peripheral blood
Time frame: 3 months
Change in soluble factors in plasma
Time frame: 3 months
Change in the composition of vaginal and intestinal microbiome
Time frame: 3 months
Change in objective stress assessed by measuring scalp hair cortisol levels
Time frame: 3 months
Adherence and anti-inflammatory status of the diet
Time frame: 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2025.
- Derived from this study: PubMed 42191188Huijs E, van der Sman L, Wirken L, Delcliseur HS, Winter EG, de Roos NM, van der Molen RG, Oosterman JM, Vigano P, Horne AW, Dolmans MM, Hoogstad-van Evert JS, Nap AW; EUmetriosis Working Group. Effectiveness of an anti-inflammatory diet intervention and cognitive behavioural therapy in endometriosis: protocol for a randomised controlled clinical trial. BMJ Open. 2026 May 26;16(5):e116964. doi: 10.1136/bmjopen-2026-116964.
- Individual participant dataSharing planned: No
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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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Anti-inflammatory diet (DI) and Cognitive behavioral therapy (CBT) in people with Endometriosis and Adenomyosis, run by Radboud University Medical Center at 5 sites in Netherlands.
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 10 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Emma Huijs (06-29698762, pearl-studie.verlgyn@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pain intensity assessed by the Numerical Rating Scale (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06332560, which also lists 1 linked publication.
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 11 Aug 2025.