Pain in Endometriosis And the Relation to Lifestyle (PEARL)

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 intervention on health related quality of life and pain symptoms in women with endometriosis. And whether the addition of CBT enhancing this effect. The secondary objective is to investigate the effect of an anti-inflammatory diet on inflammatory characteristics in serum and menstruum samples as well as the effect on the gut and vaginal microbiome.

Participants will be randomized between standard care (control group), standard care and an anti-inflammatory diet, or standard care, anti-inflammatory diet and cognitive behavioral therapy.

Participants will follow an anti-inflammatory diet based on the Dutch Dietary Guidelines 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 Overview

• Status: Not yet recruiting
• Conditions: Endometriosis
• Intervention / Treatment: Behavioral: Anti-inflammatory diet (DI); Behavioral: Cognitive behavioral therapy (CBT)

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emma Huijs; Phone Number: 06-29698762; Email: pearl-studie.verlgyn@radboudumc.nl

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboud University Medical Center
    • Contact: E Huijs, B
    • Principal Investigator: A.W. Nap, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard care (control group)
Experimental: Standard care and an anti-inflammatory diet (DI group)	Behavioral: Anti-inflammatory diet (DI); 12-week personalized dietary advice based on the Dutch Dietary Guidelines under the guidance of a dietician.; Other Names: DI
Experimental: Standard care, anti-inflammatory diet and cognitive behavioral therapy (DI + CBT group)	Behavioral: Anti-inflammatory diet (DI); 12-week personalized dietary advice based on the Dutch Dietary Guidelines under the guidance of a dietician.; Other Names: DI; Behavioral: Cognitive behavioral therapy (CBT); Seven individual sessions led by a psychotherapist. The content of the CBT will be psycho-education regarding pain mechanisms and DI.; Other Names: CBT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3 months
Change in general Quality of Life 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.	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.	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).	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).	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in sleep quality assessed by the PSQI	Sleep quality will be assessed by a self-rated questionnaire called (Pittsburgh sleep quality index) PSQI. This questionnaire contains 19 items, generating scores for seven different components. A general score can be obtained by adding up the scores of the seven components. Currently, PSQI is the most used tool in clinical and research practice assessing sleep quality. Minimum score: 0. Maximum score: 21. Higher scores indicate worse sleep quality.	3 months
Change in physical activity level assessed by the IPAQ-SF	Physical activity level will be assessed in this study to minimise confounding. Participants will fill in the (International Physical Activity Questionnaire Shor Form) IPAQ-SF, which is one of the most widely used self-report questionnaires assessing physical activity. This questionnaire assesses physical activity of the past seven days at four levels of intensity: vigorous, moderate, walking, and sitting. The IPAQ-SF sum score is expressed in PA Metabolic Equivalent of Task (MET)-minutes per day or week. A higher score corresponds to a physically more strenuous activity.	3 months
Change in Subjective stress assessed by the Perceived Stress Scale	Perceived stress will be measured using the Perceived Stress Scale (PSS), a 10-item validated psychological instrument for measuring nonspecific perceived stress. Items are designed to score how unpredictable, uncontrollable, and overloaded respondents find their lives. Minimum value: 10. Maximum value: 50. Higher score indicates a higher level of perceived stress.	3 months
Changes in pain cognitions assessed by the Pain anxiety symptom scale	The Pain anxiety symptom scale (PASS) measures anxiety caused by pain. Questions are asked about feelings of fear of pain, cognitive anxiety, avoidance behaviour, and physiological anxiety symptoms. Minimum value: 0. Maximum value: 200. Higher score indicates a higher pain anxiety.	3 months
Changes in pain cognitions assessed by the pain catastrophizing Scale	The pain catastrophizing Scale (PCS) measures the degree of pain catastrophizing of the participant by measuring elements of helplessness and pessimism in relation to the ability to cope with the pain experience. Minimum value: 0. Maximum value: 52. Higher score indicates a higher level of catastrophizing	3 months
Changes in Fatigue assessed by the checklist individual strength	The checklist Individual Strength (CIS) is a 20-item questionnaire addressing fatigue, concentration, motivation and activity over the past two weeks. The CIS is not a numerical scale.	3 months
Anti-inflammatory diet rating	At the end of the intervention period, participants will evaluate the anti-inflammatory diet with a rating on scale, and several general questions concerning the taste, cost, and feasibility. Minimum value: 1 Maximum value: 10. Higher scores indicates greater satisfaction with the diet.	At the end of the intervention (3 months), when completed the diet intervention

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometriosis; Anti-Inflammatory Agents
• Other Study ID Numbers: NL86247.091.24

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No