Clinical trial NCT02740361: Online Program to Reduce Depression in MS
Official title: International Deprexis Trial in Multiple Sclerosis (IDEMS) - a Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: National Multiple Sclerosis Society
name: Universitätsklinikum Hamburg-Eppendorf
name: Cedars-Sinai Medical Center
name: University of Missouri, Kansas City
name: Penn State University
name: King's College London
name: University Medical Center Goettingen
name: NeuroCure Clinical Research Center, Charite, Berlin
First posted: 2016-04-15
Enrollment: 279
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an international, multicenter, randomized controlled trial of an internet-based CBT intervention for depression (Deprexis) conducted in five MS centers in the US and Germany. The trial consists of a three-arm primary trial phase and an extension phase targeted at maintenance.

Detailed description: Depression is highly common in MS with a lifetime risk for major depressive disorder (MDD) as high as 25-50% and a 12-month prevalence of up to 25%, particularly in younger patients. Depression in MS has been linked to biological as well as psychological factors and substantially impacts psychosocial function. Importantly, depressive symptoms correlate with decreased quality of life, absence from work, and lower social support and are among the strongest predictors for suicidal ideation in MS patients.

Despite its immediate clinical relevance, depression in MS remains underdiagnosed and often untreated and evidence for the efficacy of pharmacological or non-pharmacological interventions for MS-associated depression is scarce. For example, guidelines recently published by the AAN concluded that evidence for pharmacotherapy and individual or group therapies for MS-depression was insufficient but recommended cognitive behavioral therapy (CBT) delivered by phone with weak level of evidence. Such approaches, however, still require availability of a trained psychotherapist.

Given the mobility problems, cognitive impairment, and fatigue typically associated with MS as well as the limited availability of psychotherapists, self-guided, automated, internet-based interventions may help to overcome treatment barriers often encountered by patients with MS. In a recent phase II randomized controlled trial (RCT) in Germany, the investigators found one such internet-based CBT program, Deprexis, to significantly reduce depressive symptoms in MS (Fischer et al., Lancet Psychiatry 2015). Despite these encouraging results, large, definitive trials of the most promising therapeutic approaches for MS-associated depression that could inform clinical practice are completely lacking.

Here, the investigators conduct a large, international, multicenter RCT of the Deprexis program to treat depression in MS patients. Patients will be recruited in five specialized MS centers in Germany (Charité Berlin and University Medical Center Hamburg) and the US (Cedars Sinai Los Angeles, University of Missouri - Kansas City, and Penn State University). The investigators plan to enroll n=400 patients who will be randomly assigned to two different versions of Deprexis (either Deprexis alone or Deprexis plus regular Email support, DeprexisPlus) for 3 months or a waitlist control group and undergo clinical assessments at baseline and month 3. In addition, the investigators will conduct long-term online follow up at month 6 and month 12.

The trial will address the following three main aims:

Aim 1: To definitively test the effectiveness of Deprexis for reducing depressive symptoms in MS at the end of treatment.

Aim 2: To determine the added value of email support for Deprexis (DeprexisPlus) in MS.

Aim 3: To explore the long-term stability of therapeutic effects (12 months) and the potential of a booster session to enhance maintenance.

Eligibility criteria: Inclusion criteria

* age \> 18
* neurologist-confirmed diagnosis of MS (all forms)
* self-reported depressive symptoms (BDI-Fastscreen \> 4)
* fluent in German or English (depending on study site),
* willingness to engage in self-administration of an iCBT intervention for 3 months and complete follow-up
* ability to travel to the outpatient center for two clinical assessments (baseline and month 3)
* internet access at home

Exclusion criteria:

* unwilling or unable to consent,
* diagnosis of bipolar or psychosis (as determined by M.I.N.I structured interview),
* substantial neurocognitive impairments such as dementia or autism
* moderate or high risk of suicide (according to MINI module C) or by clinical impression
* very severe depression that would interfere with the ability to participate in the study (based on clinical judgment by the physician at the recruitment site).
* current psychotherapy/behavioral treatments for depression
* started pharmacotherapy for depression within the last 2 months
* MS relapse or steroid treatment in the last 4 weeks
* concurrent participation in another clinical trial that includes an intervention
* refusal to saving, processing and forwarding of pseudonymized data

Primary outcomes:
measure: Beck Depression Inventory-II
timeFrame: Month 0 to Month 3
Secondary outcomes:
measure: WHO Quality of Life scale (WHO-QOL BREF)
timeFrame: Month 0 to Month 3
measure: Multiple Sclerosis Impact Scale (MSIS)
timeFrame: Month 0 to Month 3
measure: Fatigue Scale for Motor and Cognitive Functions (FSMC)
timeFrame: Month 0 to Month 3
measure: Chalder Fatigue Scale
timeFrame: Month 0 to Month 3
Other outcomes:
measure: Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)
timeFrame: Month 0 to Month 3
measure: Suicide Behaviors Questionnaire-Revised (SBQ-R)
timeFrame: Month 3
measure: Mini International Neuropsychiatric Interview, clinician rating, Version 5.0.0
timeFrame: Month 0 to Month 3
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Kansas City
country: United States
facility: University of Missouri, Kansas City
state: Kansas
city: State College
country: United States
facility: Penn State University
state: Pennsylvania
city: Berlin
country: Germany
facility: Charité University
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
Study officials:
affiliation: Charité University, Berlin
name: Stefan M Gold, PhD
role: STUDY_DIRECTOR
affiliation: Charité University, Berlin
name: Friedemann Paul, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Christoph Heesen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cedars-Sinai Medical Center
name: Nancy Sicotte, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Missouri, Kansas City
name: Jared Bruce, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Missouri, Kansas City
name: Sharon Lynch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Penn State University
name: Peter Arnett, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: King's College London
name: Rona Moss-Morris, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Goettingen
name: Tim Friede, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: GAIA Group
name: Björn Meyer, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gold SM, Friede T, Meyer B, Moss-Morris R, Hudson J, Asseyer S, Bellmann-Strobl J, Leisdon A, Issels L, Ritter K, Schymainski D, Pomeroy H, Lynch SG, Cozart JS, Thelen J, Roman CAF, Cadden M, Guty E, Lau S, Pottgen J, Ramien C, Seddiq-Zai S, Kloidt AM, Wieditz J, Penner IK, Paul F, Sicotte NL, Bruce JM, Arnett PA, Heesen C. Internet-delivered cognitive behavioural therapy programme to reduce depressive symptoms in patients with multiple sclerosis: a multicentre, randomised, controlled, phase 3 trial. Lancet Digit Health. 2023 Oct;5(10):e668-e678. doi: 10.1016/S2589-7500(23)00109-7.