MBSR in Rheumatoid Arthritis Patients With Controlled Disease But Persistent Depressive Symptoms

Rheumatoid Arthritis Clinical Trial

— PARIS-D  

Official title:

Pilot Study of Mindfulness-Based Stress Reduction (MBSR) in Patients With Rheumatoid Arthritis That Still Screen Depressed, Despite Adequate Control of Inflammation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03514355
• Other study ID #: MP-31-2017-1558
• Status: Completed
• Phase: N/A
• Start date: September 4, 2017
• Est. completion date: September 29, 2021

Study information

• Verified date: September 2021
• Source: Université de Sherbrooke
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: September 29, 2021
• Est. primary completion date: December 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Depression
• Depressive Symptoms
• Rheumatoid Arthritis

Intervention

Behavioral:
• Mindfulness-Based Stress Reduction
8 weekly 2.5 h sessions plus one day of practice

Locations

Country	Name	City	State
Canada	Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Estrie - CHUS	Sherbrooke	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Université de Sherbrooke	Canadian Initiative for Outcomes in Rheumatology Care

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Spontaneous variation in Center for Evaluation Studies - Depression (CES-D) score in controls	to estimate the variations in CES-D scores (range 0-60; depression suggested if at least 16) between baseline and 6 months (i.e. about 3 months after the end of MBSR) in the randomized controls	6 months
Secondary	Numbers of patients recruited using current recruitment strategy	adjust recruitment strategy to obtain an optimal one, that is being able to form randomized groups of 15 patients in the MBSR group and 15 controls, every 6 months over 12 months	6 months
Secondary	Impact of Mindfulness-Based Stress Reduction (MBSR) on Patient evaluation of disease activity of Rheumatoid arthritis	to estimate the impact of MBSR on Patient evaluation of disease activity of Rheumatoid arthritis (range 0-10, 0 meaning no disease activity and 10 the most active disease possible according to the patient) between baseline and 6 months following MBSR	6 months
Secondary	Impact of Mindfulness-Based Stress Reduction (MBSR) on Center for Epidemiologic Studies Depression Scale Revised (CES-D) depressive symptoms)	to estimate the impact of MBSR on Center for Epidemiologic Studies Depression Scale Revised between baseline and 6 months following MBSR. The scale goes from 0 to 60 (60 meaning the maximal depressive symptoms possible). An individual from the general population with a score above 16 is considered with possible depression and a clinical assessment for depression may be justified; the equivalent threshold in patients with rheumatoid arthritis is 19.	6 months
Secondary	Impact of MBSR on anxiety	estimate impact of MBSR (versus control) between baseline and 6 months on anxiety measured using the Generalized Anxiety Disorder-7 (GAD-7 scale from 0 to 21, 21 being the worst possible score)	6 months
Secondary	Impact of MBSR on pain	estimate impact of MBSR (versus control) between baseline and 6 months on pain (Visual Analog Scale goes from 0-100, with 100 indicating the most severe possible pain)	6 months
Secondary	Impact of MBSR on fatigue	estimate impact of MBSR (versus control) between baseline and 6 months on fatigue (Visual Analog Scale goes from 0 to100, with 100 indicating the most severe fatigue possible)	6 months
Secondary	Beck Depression Inventory (BDI)	Impact of MBSR (versus control) between baseline and 6 months on BDI scores (range 0-63, 63 being the worst possible score)	6 months
Secondary	Numbers of patients with complete Biomarker collection	validate our methods of biomarker collection to attain more than 90% of usable samples	6 months
Secondary	Numbers of patients with adverse events linked to MBSR	track adverse events associated with MBSR in RA patients according to CTCAE v4.03	6 months