About this trial
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).
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Confirmed diagnosis of endometriosis via ultrasound, MRI or surgery*
NRS pain score > 4*
Age from 17 years
Premenopausal status
Disqualifiers
Recurrent miscarriages (> 2)
Eating disorder
Diagnosed with Crohn's disease, Ulcerative Colitis, short bowel syndrome or another chronic inflammatory disease
Self-reported celiac disease
Trial design
Parallel
Treatments tested in this trial
Anti-inflammatory diet (DI)
Behavioral12-week personalized dietary advice based on the Dutch Dietary Guidelines under the guidance of a dietician.
Cognitive behavioral therapy (CBT)
BehavioralSeven individual sessions led by a psychotherapist. The content of the CBT will be psycho-education regarding pain mechanisms and DI.
Treatment groups
Trial outcomes
Primary outcomes
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.
Secondary outcomes
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.
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.
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.
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.
Other outcomes
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.
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.
Change in subjective stress assessed by the PSS
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.
Changes in pain cognitions assessed by the PASS
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.
Sponsors and contacts
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Radboud University Medical Center
Lead sponsor
ZonMw: The Netherlands Organisation for Health Research and Development
Collaborator
Belgian Volition SRL
Collaborator
ASSOCIATION OF PEOPLE WITH ENDOMETRIOSIS I AM 1 IN 10
Collaborator
Wageningen University and Research
Collaborator
Endometriosis UK
Collaborator
University College Cork
Collaborator
SVEUCILISTE U ZAGREBU MEDICINSKI FAKULTET
Collaborator
UNIWERSYTET MEDYCZNY W LUBLINIE
Collaborator
University of Edinburgh
Collaborator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Collaborator
Université Catholique de Louvain
Collaborator
University of Bonn
Collaborator
Biopsychology
Collaborator
Horizon Europe
Collaborator