Clinical trial NCT03514355: MBSR in Rheumatoid Arthritis Patients With Controlled Disease But Persistent Depressive Symptoms
Official title: Pilot Study of Mindfulness-Based Stress Reduction (MBSR) in Patients With Rheumatoid Arthritis That Still Screen Depressed, Despite Adequate Control of Inflammation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rheumatoid Arthritis
Depressive Symptoms
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
Collaborators: name: Canadian Initiative for Outcomes in Rheumatology Care
First posted: 2018-05-02
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization of consenting eligible patients in intervention and control groups using separate permutated random blocks of 4
Primary purpose: SUPPORTIVE_CARE

Brief summary: Despite their efficacy at controlling joint inflammation, current treatments of rheumatoid arthritis (RA) leave up to 40% of patients into non-remission.

Non-remission is most frequently due to persistently negative self-reported global impact of RA, and not to remaining swollen joints or elevated levels of acute phase reactants. In a cohort of recent-onset RA patients diagnosed early and treated to remission (Sherbrooke Early Undifferentiated PolyArthritis (EUPA) cohort), treatment of active disease rapidly led to reduced depressive symptoms in most, but 20% still expressed elevated depressive symptoms (using the CES-D screening tool) after a mean of 7 months. Elevated CES-D scores at this early time strongly predicted never reaching remission over the following 4 years. Elevated CES-D scores were strongly correlated with increased levels of patient-related outcomes (PROs such as fatigue, pain, sleep quality, stiffness and functional limitation), but not with joint or systemic inflammation. In fact, 80% of patients expressing depressive symptoms had controlled joint disease at the same visit. The investigators propose that addressing depressive symptoms will improve RA patients' symptoms and quality of life. In clinical practice, the best indicator of depressive symptoms is the presence of a disconnect between the Patient's (Pt-VAS) and the Physician's (MD-VAS) evaluation of disease activity in patients without objective signs of inflammation.

This pilot study will explore the feasibility and acceptability of testing MBSR in these patients. It will assess over 6 months the changes in depressive symptoms and PROs both in controls and MBSR-treated patients. If positive, the investigators plan to complete a multicenter 6-month Randomized Clinical trial (RCT) (with a 2 year follow up) to formally address the risks/benefits of group MBSR interventions in RA patients with controlled inflammatory disease but positive disconnect between Pt-VAS and MD-VAS.

Detailed description: This is a pilot project for a pragmatic multisite, 6-month, two arm RCT of an MBSR intervention in RA patients expressing depressive symptoms despite controlled joint inflammation, on measures of depressive symptoms (Primary outcome). The investigators will also explore the impact of MBSR on significant PROs (e.g. fatigue, pain, Pt-VAS, anxiety) further translating into lower SDAI scores post-MBSR, and the feasibility of determining if improvement may be mediated though better adherence to treatment and/or through a modification of inflammation-related biomarkers.

During the present 1-year pilot study, the investigators propose to randomize 50 patients, and offer 2 MBSR groups of ≈13 patients each. Due to the bidirectional relationship between RA and depression, MBSR will be studied in patients receiving stable doses of arthritis medications during remission or low disease activity. To avoid recruitment based on thresholds of composite scores (e.g. SDAI) that are strongly impacted by depression-sensitive variables, such as Patient global evaluation of disease activity (PtVAS) and tender joint counts (TJC), the investigators will use a Swollen Joint Count (SJC) ≤2 out of 66 joints and C-Reactive Protein (CRP) ≤8 mg/L ('objective' measures) to define controlled disease. As SJC is the major determinant for RA treatment change in clinical practice, short-term RA treatment changes are unlikely in the recruited patients.

Controlled RA patients reporting Pt-VAS superior to MD-VAS by at least 20/100 units will be recruited. Blinded clinical assessors will determine the joint counts and the Examiner global evaluation of disease activity (EVAS) to determine SDAI scores at baseline and at 6 months. The French Canadian version of the CES-D and the Beck Depression Inventory to assess the importance of depressive symptoms, as well as 0-100 VAS scales (fatigue; sleep; pain; PtVAS) and Health Assessment Questionnaire (HAQ) will be obtained at both visits. Reporting will conform to the CONSORT recommendations for pilot studies.

This study reflects clinical practice, where there is heterogeneity in duration of disease, gender, age, type and dose of RA drugs used, as well as type and dose of antidepressants (when used). While the investigators suggest that RA drugs remain constant over the 6-month intervention period, treating physicians will be free to modify treatment if clinically indicated. Antidepressant use will not be an exclusion criterion.

For pragmatic reasons (e.g. uneven availability and expertise of primary care physician's (PCP), unknown effect size of the intervention), the investigators will not include a second active treatment arm with optimization of antidepressants. Instead, the investigators will inform in writing treating PCPs of their patient participation to the study and of the disconnect between Pt-VAS and MD-VAS. Changes to arthritis and depression drugs will be tracked and controlled for in analyses. For patients' safety, psychological contraindications to MBSR will be screened at baseline during a phone interview by Dr Françoise Gendron who will direct the MBSR sessions, and patients with contraindications excluded.

Eligibility criteria: Inclusion Criteria:

1. ≥18 years, with stable (3 months) disease modifying antirheumatic drugs (DMARDs) and/or biologic-treated RA (meeting classification criteria)
2. both ≤2/66 SJC plus CRP ≤8 mg/L
3. Patient Evaluation of disease activity (Pt-VAS) ≥20 higher than Physician Evaluation of Disease Activity (MD-VAS).

Exclusion Criteria:

1. Inability to consent (e.g. not fluent in French, dementia) or to participate in groups;
2. Active vasculitis, SJC ≥3, CRP ≥8, arthritis drug changes (i.e. addition or increase of DMARDs or biologics or oral corticosteroids) during the last 3 months

Primary outcomes:
measure: Spontaneous variation in Center for Evaluation Studies - Depression (CES-D) score in controls
timeFrame: 6 months
Secondary outcomes:
measure: Numbers of patients recruited using current recruitment strategy
timeFrame: 6 months
measure: Impact of Mindfulness-Based Stress Reduction (MBSR) on Patient evaluation of disease activity of Rheumatoid arthritis
timeFrame: 6 months
measure: Impact of Mindfulness-Based Stress Reduction (MBSR) on Center for Epidemiologic Studies Depression Scale Revised (CES-D) depressive symptoms)
timeFrame: 6 months
measure: Impact of MBSR on anxiety
timeFrame: 6 months
measure: Impact of MBSR on pain
timeFrame: 6 months
measure: Impact of MBSR on fatigue
timeFrame: 6 months
measure: Beck Depression Inventory (BDI)
timeFrame: 6 months
measure: Numbers of patients with complete Biomarker collection
timeFrame: 6 months
measure: Numbers of patients with adverse events linked to MBSR
timeFrame: 6 months
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Estrie - CHUS
state: Quebec
Study officials:
affiliation: Université de Sherbrooke
name: Gilles Boire, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: