Randomized Intervention Study of Mindfulness-Based Stress-Reduction to Improve the Quality of Life and Immune Regulation in Patients With Crohn's Disease

1. Overall objectives:

2. Primary outcome: To determine whether mindfulness-based stress reduction will lead to a better health-related quality-of-life by use of three questionnaires:

• the Crohn's disease specific SIBDQ (Short Inflammatory Bowel Disease Questionnaire, with mean score and 4 subscales: bowel, systemic, social, emotional)

• SF-12 (MOS Short-Form-12) which is derived from the generic SF-36 used in our previous research (SF-36 measures a Physical Health Summary Score comprised of physical functioning, role-physical, bodily pain and general health, and a Mental Health Summary Score comprised of vitality, role-emotional, social functioning and mental health).
• EQ-5D (EuroQol questionnaire, for calculation of utility weights)

2. Secondary outcomes: improvement in mindfulness (FMI, Freiburg Mindfulness Inventory); reduction of stress, anxiety and depression (BSI - Brief Symptom Inventory, GSI - General Severity Index stress measure, MSPSS- Multidimensional Scale of Perceived Social Support, PSS-4 Perceived Stress Scale, LEQ- life events questionnaire); better satisfaction with life (SWLS, Satisfaction with Life Scale); improved family function (FAD, Family Assessment Device); pain reduction (HBI, Harvey-Bradshaw Index of activity of Crohn's disease); less fatigue (FACIT Fatigue Scale); better coping with disease (COPE: Brief Cope Inventory - Brief Coping Operations Preference Enquiry); better performance at work (WPAI, Work Productivity and Activity Impairment) and cost estimation. Significant changes in the scores of these questionnaires, based on our current work comparing P-HBI remission versus active disease, are the following (all are given in points, except WPAI is percent): SIBDQ 6, SWLS 5, FAD 0.15, COPE dysfunctional 2.5, COPE emotion-focused 0.7, COPE problem-focused 0.6, WPAI time missed 14, WPAI percent impairment 29, WPAI work impairment 28, WPAI activity impairment 30, GSI 0.6, BSI anxiety 0.6, BSI depression 0.6. We did not use the SF-12, EQ-5D, MSPSS, PSS-4 and the FACIT Fatigue Scale in our previous research and will look at reports in the literature and our newly acquired data to determine what are significant improvements.

3. Before and at the end of each intervention session a short assessment of patient's subjective units of distress (SUDS) will be done, as per Wolpe, Joseph (1969), The Practice of Behavior Therapy, New York: Pergamon Press, and the 4 question Short-Form Perceived Stress Scale, as per Warttig et al, J Health Psychology 2013;18:1617-28.

4. Correlations of psychological measures with demography, economic status, HBI, immune regulation, telomere shortening, fMRI data, changes in composition of microbiota. Change in biophysical parameters as sleep physical activity & pulse rate.

5. To determine whether the intervention is cost-saving or cost-effective, by prospective monitoring of resource use and indirect costs.

6. To determine whether the intervention can be given effectively using telemedicine with Skype or alternative software.

7. To study patient acceptability of the intervention, including recruitment and drop-out rate, and the adherence rate to home practice of the stress reduction measure taught.

8. Expected outcomes

9. Reduced HBI, improvement of all the psychological measures including both quality-of-life and satisfaction with life, less stress, less fatigue, more use of adaptive coping strategies, with no clear improvements in the control group. Improvement in biophysical parameters as sleep physical activity & pulse rate.

10. The research will identify the best form of delivering the interventional therapy and if it is cost-saving or cost-effective.

11. Confirmation of the reliability of measurements of modification of immune regulation mechanisms and telomere length, grey matter thickness and composition of the microbiota.

12. Glucocorticoid resistance and related laboratory determinations on patients' leukocytes will add to understanding the biological mechanisms associated with stress-induced pathogenic autoimmunity in the patients in a sex-dependent manner. This will add to our understanding the biological mechanisms associated with stress in Crohn's disease.

13. Work plan and methodology

a. Patient recruitment i. Patients: 200 patients being treated at all the participating hospitals (Soroka Medical Center, Rambam Health Campus, Sheba Medical Center, Rabin Medical Center, Shaare Zedek Medical Center), which all have electronic records of large cohorts of patients with Crohn's disease and by advertising through patient support groups and institutions upon approval. The recruitment of patients will be offered in all the hospitals. Preference will be given to patients who have participated in the previous IIRN study and are now participating in the new IIRN studies proposed by the other hospitals, and those patients in higher risk groups (poorer men, female gender, etc.).