Pain in Endometriosis And the Relation to Lifestyle

Not Applicable

Recruiting

• Conditions: Endometriosis; Adenomyosis

• Registration Number: NCT06332560
• Lead Sponsor: Radboud University Medical Center

Brief 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 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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-03-13
• Study First Submitted QC: 2024-03-20
• Study First Posted: 2024-03-27
• Study Start: 2024-10-04
• Status Verified: 2024-12
• Last Update Submitted: 2025-08-05
• Last Update Posted: 2025-08-11
• Primary Completion: 2027-05
• Study Completion: 2027-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 250

Inclusion Criteria

• 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*
• 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.

Exclusion Criteria

• 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

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in Pain intensity assessed by the Numerical Rating Scale	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.

Secondary Outcome Measures

Name	Time	Method
Change in health related quality of life assessed by the Endometriosis Health Profile 30	3 months	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.
Change in inflammatory characteristics in menstruum	3 months	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.
Change in general quality of llife assessed by the Short Form 36	3 months	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.
Change in inflammatory charecteristics in peripheral blood	3 months	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.
Change in soluble factors in plasma	3 months	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.
Change in the composition of vaginal and intestinal microbiome	3 months	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.
Change in objective stress assessed by measuring scalp hair cortisol levels	3 months	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).
Adherence and anti-inflammatory status of the diet	3 months	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).

Trial Locations

Locations (5)

Jeroen Bosch Hospital (JBZ); 🇳🇱 's-Hertogenbosch, Netherlands

Rijnstate Hospital; 🇳🇱 Arnhem, Netherlands

Amphia; 🇳🇱 Breda, Netherlands

Catharina Hospital; 🇳🇱 Eindhoven, Netherlands

Radboud University Medical Center; 🇳🇱 Nijmegen, Netherlands