Clinical trial NCT04646785: Mindfulness-based Cognitive Therapy for Patients With Inflammatory Bowel Disease
Official title: Mindfulness-based Cognitive Therapy to Improve Stress and Sleep in Patients With Inflammatory Bowel Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Inflammatory Bowel Diseases
Keywords: randomized controlled trial
mindfulness-based cognitive therapy
effectiveness
psychological distress
sleep
fatigue
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Jeroen Bosch Ziekenhuis
name: Rijnstate Hospital
name: Canisius-Wilhelmina Hospital
name: Donders Institute for Brain, Cognition and Behaviour
First posted: 2020-11-30
Enrollment: 142
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, multicenter, clinical trial with assessments at baseline, post treatment (3 months later) and follow-ups at 6, 9 and 12 months after baseline.
Primary purpose: SUPPORTIVE_CARE

Brief summary: Considering the limited availability of psychosocial interventions for IBD, this study aims to investigate MBCT as an adjunctive treatment to treatment as usual to reduce psychological stress and improve sleep quality/regularity in patients with IBD who report elevated stress levels. The study will have a follow-up duration of 12 months from baseline.

Detailed description: Introduction:

Inflammatory bowel diseases (IBD) are chronic inflammatory diseases of the intestinal tract, consisting of crohn's disease (CD) and ulcerative colitis (UC). In The Netherlands, there are about 90,000 IBD patients, mainly young adults who are in a turbulent part of their life with starting a family and career. The prevalence of IBD seems to be rising. The peak incidence is between 15 and 30 years. The disease is characterized by periods of disease activity (flares) alternating with periods of (clinical) remission. Physical symptoms include abdominal pain, diarrhea, rectal bleeding and fatigue. Although the arsenal of drugs has increased in recent decades, there is no cure for the disease and patients are usually long-term treated with different (immunosuppressive) medications. Nevertheless, at this moment, we are only partially able to keep our IBD patients in remission.

Even in those in remission, IBD is associated with increased levels of psychological stress, with estimated prevalence rates of 21% for depressive symptoms and 35% for anxiety symptoms. In periods of disease activity, prevalence of elevated anxiety levels was even found to be as high as 75.6%. Besides psychological stress, IBD patients in remission report lower quality of life compared to the general population. This is due to the physical symptoms but also to fatigue, worries, anxiety, depression, impaired satisfaction with social role and sleep disturbances. More than 40 % of the IBD patients experience fatigue. This may contribute to the higher sick leave days and higher work impairment rates in quiescent IBD, causing high societal costs. In addition, poor sleep seems common in individuals with IBD and has been linked to disease activity and shown as a predictor for subclinical inflammation and a risk factor for relapse and poorer outcomes.

Mindfulness training, typically in the form of mindfulness-based stress reduction (MBSR) or mindfulness-based cognitive therapy (MBCT), is a psychosocial group-based intervention that has been shown to reduce psychological distress and improving quality of life, both in patients with mental health problems and those with chronic diseases such as diabetes, cancer, cardiovascular disease, rheumatoid arthritis and fibromyalgia. Mindfulness training focuses on the progressive acquisition of mindful awareness to better cope with negative repetitive thoughts and feelings, and for that reason may be a good option to reduce psychological stress and fatigue, and improve quality of life in patients with chronic conditions including IBD.

Although the available literature on the effectiveness of mindfulness-based interventions for IBD is still relatively scarce, a recent meta-analysis showed significant benefits in terms of stress, depression, and quality of life. However, the variety in types of interventions was rather high, and individual studies typically suffered from methodological limitations, including small sample size, poor blinding of the outcome assessors, incomplete data reporting and a relative lack of fidelity measures. Therefore, it seems warranted to conduct a high-quality, multicenter randomized controlled trial investigating the effectiveness of MBCT to improve stress, sleep quality, and quality of life.

Aims:

Considering the limited availability of psychosocial interventions for IBD, this study aims to investigate MBCT as an adjunctive treatment to TAU to reduce psychological stress in patients with IBD who report elevated stress levels. In addition, we aim to improve sleep quality/regularity and fatigue, IBD-related quality of life, perceived control over IBD, clinical indicators (fecal calprotectin, c-reactive protein levels, Harvey Brashaw Index for CD, Simple Clinical Colitis Activity Index for UC), IBD-related flare. We also aim to improve repetitive negative thinking, mindfulness skills, self-compassion skills, and positive mental health. We will investigate whether improving sleep quality may be one of the pathways through which mindfulness may help reduce psychological distress and improve quality of life in IBD (working mechanism).

Method:

A two-armed randomized, multicenter, parallel group pragmatic trial comparing Mindfulness-Based Cognitive Therapy (MBCT) vs. Treatment As Usual (TAU) for reducing psychological distress in distressed patients with Inflammatory Bowel Disease (IBD). Assessments will be conducted at baseline, post treatment (3 months) and follow-ups at 6, 9, and 12 months. Objective sleep measures will be taken at baseline, post treatment and 12 months.

The control group will receive treatment as usual (TAU) according to Dutch and European IBD treatment guidelines. The intervention group will receive Mindfulness-Based Cognitive Therapy (MBCT) in addition to TAU. The MBCT protocol that will be used is based on the protocol published by Segal, Williams and Teasdale. MBCT consists of eight weekly 2.5h group sessions, a six-hour silent day and daily home practice assignments guided by audio files. Mindfulness is characterized by deliberate, non-judging and sustained moment-to-moment awareness. Health related benefits include enhanced emotional processing and coping regarding the effects of chronic illness and stress, improved self-efficacy and control, and a more accepting attitude towards difficult emotions, thought and bodily sensations. Psycho-education and interactive dialogue typically focus on stress management, balancing activities, lifestyle factors, and strategies to stay well in the future (relapse prevention). Each group will be comprising 8-12 participants. MBCT courses will be taught on site by qualified mindfulness teachers. Teacher competency will be assessed with the Mindfulness-Based Interventions - Teaching Assessment Criteria, using a random selection of videotaped sessions, assessed by expert teachers who have been trained to use these assessment criteria.

Eligibility criteria: Inclusion Criteria:

* Confirmed IBD diagnosis of Crohn's disease (CD), Ulcerative colitis (UC) or Indeterminate colitis (IC)
* Current IBD remission (Calprotectin \< 250 mg/kg) since at least three months
* Hospital Anxiety and Depression Scale-score of \>=11, indicating at least mild levels of psychological distress (Vodermaier 2011).
* Age of 16 or older
* Taking no IBD medication or on a stable dose of 5-ASA products, immunosuppressive medication, or biologics for at least three months prior to enrollment.

Exclusion Criteria:

* Severe psychiatric disorders (e.g. acute suicidality, psychosis)
* Current alcohol or drug dependency
* Untreated anemia
* Prior participation in an 8-week MBSR or MBCT-programme

Primary outcomes:
measure: Psychological distress
timeFrame: Change between baseline and 3 months
measure: Psychological distress
timeFrame: Change between 3 and 12 months
Secondary outcomes:
measure: Objective sleep quality
timeFrame: Change between baseline and 3 months
measure: Objective sleep quality
timeFrame: Change between 3 and 12 months
measure: Subjective sleep quality
timeFrame: Change between baseline and 3 months
measure: Subjective sleep quality
timeFrame: Change between 3 and 12 months
measure: Fatigue
timeFrame: Change between baseline and 3 months
measure: Fatigue
timeFrame: Change between 3 and 12 months
measure: IBD-related quality of life
timeFrame: Change between baseline and 3 months
measure: IBD-related quality of life
timeFrame: Change between 3 and 12 months
measure: Perceived control over IBD
timeFrame: Change between baseline and 3 months
measure: Perceived control over IBD
timeFrame: Change between 3 and 12 months
measure: Calprotectin
timeFrame: Change between baseline and 3 months
measure: Calprotectin
timeFrame: Change between 3 and 12 months
measure: C-reactive protein levels
timeFrame: Change between baseline and 3 months
measure: C-reactive protein levels
timeFrame: Change between 3 and 12 months
measure: Clinical disease activity
timeFrame: change between baseline and 3 months
measure: Clinical disease activity
timeFrame: change between 3 and 12 months
measure: Repetitive negative thinking
timeFrame: Change between baseline and 3 months
measure: Repetitive negative thinking
timeFrame: Change between 3 and 12 months
measure: Mindfulness skills
timeFrame: Change between baseline and 3 months
measure: Mindfulness skills
timeFrame: Change between 3 and 12 months
measure: Positive mental health
timeFrame: Change between baseline and 3 months
measure: Positive mental health
timeFrame: Change between 3 and 12 months
measure: Self-compassion
timeFrame: Change between baseline and 3 months
measure: Self-compassion
timeFrame: Change between 3 and 12 months
measure: Costs
timeFrame: 12 months
measure: Health-related quality of life
timeFrame: 12 months
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Center
state: Gelderland
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
Study officials:
affiliation: Radboud University Medical Center
name: Anne Speckens, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Jeroen Bosch Ziekenhuis
name: Loes Nissen, Dr.
role: STUDY_CHAIR
affiliation: Radboud University Medical Center
name: Marloes Huijbers, Dr.
role: STUDY_CHAIR
References:
citation: Ewais T, Begun J, Kenny M, Rickett K, Hay K, Ajilchi B, Kisely S. A systematic review and meta-analysis of mindfulness based interventions and yoga in inflammatory bowel disease. J Psychosom Res. 2019 Jan;116:44-53. doi: 10.1016/j.jpsychores.2018.11.010. Epub 2018 Nov 14.
citation: Neuendorf R, Harding A, Stello N, Hanes D, Wahbeh H. Depression and anxiety in patients with Inflammatory Bowel Disease: A systematic review. J Psychosom Res. 2016 Aug;87:70-80. doi: 10.1016/j.jpsychores.2016.06.001. Epub 2016 Jun 6.
citation: Knowles SR, Graff LA, Wilding H, Hewitt C, Keefer L, Mikocka-Walus A. Quality of Life in Inflammatory Bowel Disease: A Systematic Review and Meta-analyses-Part I. Inflamm Bowel Dis. 2018 Mar 19;24(4):742-751. doi: 10.1093/ibd/izx100.
citation: IsHak WW, Pan D, Steiner AJ, Feldman E, Mann A, Mirocha J, Danovitch I, Melmed GY. Patient-Reported Outcomes of Quality of Life, Functioning, and GI/Psychiatric Symptom Severity in Patients with Inflammatory Bowel Disease (IBD). Inflamm Bowel Dis. 2017 May;23(5):798-803. doi: 10.1097/MIB.0000000000001060.
citation: Chavarria C, Casanova MJ, Chaparro M, Barreiro-de Acosta M, Ezquiaga E, Bujanda L, Rivero M, Arguelles-Arias F, Martin-Arranz MD, Martinez-Montiel MP, Valls M, Ferreiro-Iglesias R, Llao J, Moraleja-Yudego I, Casellas F, Antolin-Melero B, Cortes X, Plaza R, Pineda JR, Navarro-Llavat M, Garcia-Lopez S, Robledo-Andres P, Marin-Jimenez I, Garcia-Sanchez V, Merino O, Algaba A, Arribas-Lopez MR, Banales JM, Castro B, Castro-Laria L, Honrubia R, Almela P, Gisbert JP. Prevalence and Factors Associated With Fatigue in Patients With Inflammatory Bowel Disease: A Multicentre Study. J Crohns Colitis. 2019 Aug 14;13(8):996-1002. doi: 10.1093/ecco-jcc/jjz024.
citation: van der Valk ME, Mangen MJ, Leenders M, Dijkstra G, van Bodegraven AA, Fidder HH, de Jong DJ, Pierik M, van der Woude CJ, Romberg-Camps MJ, Clemens CH, Jansen JM, Mahmmod N, van de Meeberg PC, van der Meulen-de Jong AE, Ponsioen CY, Bolwerk CJ, Vermeijden JR, Siersema PD, van Oijen MG, Oldenburg B; COIN study group and the Dutch Initiative on Crohn and Colitis. Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFalpha therapy: results from the COIN study. Gut. 2014 Jan;63(1):72-9. doi: 10.1136/gutjnl-2012-303376. Epub 2012 Nov 7.
citation: Burisch J, Jess T, Martinato M, Lakatos PL; ECCO -EpiCom. The burden of inflammatory bowel disease in Europe. J Crohns Colitis. 2013 May;7(4):322-37. doi: 10.1016/j.crohns.2013.01.010. Epub 2013 Feb 8.
citation: Qazi T, Farraye FA. Sleep and Inflammatory Bowel Disease: An Important Bi-Directional Relationship. Inflamm Bowel Dis. 2019 Apr 11;25(5):843-852. doi: 10.1093/ibd/izy334.
citation: Segal, Z. V., Williams, J. M. G., & Teasdale, J. D. (2013). Mindfulness-based cognitive therapy for depression (second).
citation: Guo J, Wang H, Luo J, Guo Y, Xie Y, Lei B, Wiley J, Whittemore R. Factors influencing the effect of mindfulness-based interventions on diabetes distress: a meta-analysis. BMJ Open Diabetes Res Care. 2019 Dec 11;7(1):e000757. doi: 10.1136/bmjdrc-2019-000757. eCollection 2019.
citation: Cillessen L, Johannsen M, Speckens AEM, Zachariae R. Mindfulness-based interventions for psychological and physical health outcomes in cancer patients and survivors: A systematic review and meta-analysis of randomized controlled trials. Psychooncology. 2019 Dec;28(12):2257-2269. doi: 10.1002/pon.5214. Epub 2019 Sep 11.
citation: Scott-Sheldon LAJ, Gathright EC, Donahue ML, Balletto B, Feulner MM, DeCosta J, Cruess DG, Wing RR, Carey MP, Salmoirago-Blotcher E. Mindfulness-Based Interventions for Adults with Cardiovascular Disease: A Systematic Review and Meta-Analysis. Ann Behav Med. 2020 Jan 1;54(1):67-73. doi: 10.1093/abm/kaz020.
citation: Zhou B, Wang G, Hong Y, Xu S, Wang J, Yu H, Liu Y, Yu L. Mindfulness interventions for rheumatoid arthritis: A systematic review and meta-analysis. Complement Ther Clin Pract. 2020 May;39:101088. doi: 10.1016/j.ctcp.2020.101088. Epub 2020 Jan 11.
citation: Haugmark T, Hagen KB, Smedslund G, Zangi HA. Mindfulness- and acceptance-based interventions for patients with fibromyalgia - A systematic review and meta-analyses. PLoS One. 2019 Sep 3;14(9):e0221897. doi: 10.1371/journal.pone.0221897. eCollection 2019.
citation: Crane RS, Eames C, Kuyken W, Hastings RP, Williams JM, Bartley T, Evans A, Silverton S, Soulsby JG, Surawy C. Development and validation of the mindfulness-based interventions - teaching assessment criteria (MBI:TAC). Assessment. 2013 Dec;20(6):681-8. doi: 10.1177/1073191113490790. Epub 2013 Jun 21.