Clinical trial NCT06804954: Transdiagnostic Online CBT Vs. Care As Usual for Primary Care Patients with Subsyndromal Mental Ill-health ( PRIMARITA-2 )
Official title: Internet-based Transdiagnostic Cognitive Behavior Therapy and Care As Usual for Primary Care Patients with Mental Ill-health (RCT-2: Subsyndromal Mental Ill-health)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mental Ill-health
Keywords: Primary Care
Transdiagnostic CBT
Online treatment
Subsyndromal mental ill-health
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Region Stockholm
First posted: 2025-02-03
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this randomized controlled trial is to investigate if online transdiagnostic cognitive behavior therapy (CBT) can be effective in the treatment of subsyndromal mental ill-health in adult primary care patients. The main aim is to investigate:

if online transdiagnostic CBT yields superior symptomatic improvement compared to care-as-usual when given in a primary care context to patients with mental ill-health.

Researchers will compare online transdiagnostic CBT to primary care as usual to see if psychiatric symptoms can be reduced.

Participants will be randomized to online transdiagnostic CBT or primary care as usual. Participants in online transdiagnostic CBT will receive a cognitive behavioral treatment provided through a secure web platform in which psychoeducation, worksheets, and exercises are presented in online modules similar to chapters in a book. Participants will receive weekly written feedback on their work and progress by a therapist who gives gradual access to the treatment modules. The lion's share of the contact between the therapist and the patient thus takes place through messages (similar to email) in the online treatment platform.

Participants randomized to care as usual will receive health care services as usual in primary care. As this comparator is intended to reflect real routine primary care, the interventions will not be controlled by the research project, but the investigators expect that participants will receive an active treatment.

Detailed description: Background: A large proportion of primary care patients with mental ill-health do not meet criteria for a manifest specific psychiatric disorder, but have subsyndromal mental ill-health that nonetheless requires treatment. The available research litterature regarding how to treat this patient group is scarce and the high demand for therapeutic services in primary care typically leads to low treatment accessibility. One possible and practical therapeutic solution is online transdiagnostic CBT, which draws on shared underlying mechanisms and is resource-efficient. There is still clear limitations in its evidence-base there is little data on how this method compares to primary care as usual for this patient group.

Purpose and aims: The overall purpose of the current trial is to build evidence for an accessible online transdiagnostic CBT for primary care patients with subsyndromal mental-ill health. A randomized controlled trial will be conducted where adult primary care patients with mental ill-health (but without manifest specific psychiatric disorder) will receive online transdiagnostic CBT or care as usual.

The main aim (I) of the study is to investigate if online transdiagnostic CBT yields superior symptomatic improvement compared to care-as-usual when given in a primary care context to patients with subsyndromal mental ill-health. Secondary aims are to investigate (II) if the treatment conditions are associated with improvement in quality of life, functional impairment, and neuroticism (III) moderators of treatment outcome, (IV) mediators of improvement, and (V) the cost-effectiveness (including effects on sickness absence) of online transdiagnostic CBT compared to primary care-as-usual. Should the trial fail to show a significant difference on the primary outcome, a secondary aim will also be to (VI) investigate if online transdiagnostic CBT is non-inferior to primary care as usual in reducing psychiatric symptoms.

Methods: This is a randomized controlled superiority trials where consecutively recruited adult primary care patients (N=500) are allocated in a 1:1 ratio to Internet-delivered transdiagnostic CBT or to primary care-as usual. This trial is part of larger project comprising two twin randomized controlled trials that are conducted in parallel where the difference between them is that the current trial will include patients with subsyndromal mental ill-health whereas the other (separately registered with clinicaltrials.gov) will include patients with a manifest psychiatric disorder.

Participants are consecutively recruited from the regular influx of primary care patients. Gustavsberg Primary Health Care Center in Region Stockholm, Sweden, is the basis, but additional primary care centers will be engaged to facilitate the recruitment and treatment of participants. The investigators expect that 10 to 20 primary care centers in Region Stockholm will be engaged for the recruitment and treatment of participants.

Patients who seek help for common mental health problems will be asked if they are interested in applying for the study. Those interested will undergo an assessment interview with a licensed clinician where all inclusion criteria are checked.

Measurements: See section Outcome Measures.

Treatment conditions: See section Arms and Interventions.

Data analysis: Change in the primary outcome measure will be analyzed using mixed effects linear regression. Fixed predictors in these analyses will be time, group and their interaction effect while taking individual variation in baseline symptom levels and change over time into account, i.e., random intercept and slope. Change from baseline to 10-week follow-up will be the primary endpoint. Power analyses show that to have 90% power to detect an effect size of d=0.25 (α=.05), given a correlation between measurements of 0.7, and an expected attrition of 15-20%, 250 participants will be needed in each arm (total sample size N=500). Should the main analysis show that there is a non-significant difference on the primary outcome, the investigators will conduct a secondary analysis of whether online transdiagnostic CBT is non-inferior to primary care-as-usual where the non-inferiority margin on the primary outcome is set to d=0.25, i.e., the bound of the one-sided 95% confidence interval must be within this margin for non-inferiority to be demonstrated. With 500 participants, 15-20% attrition, and a true null effect of zero, the study will have approximately 80% power to detect non-inferiority.

Eligibility criteria: Inclusion Criteria:

To be included patients have to:

1. To be included patients have to: (a) have a subsyndromal mental health problem concerning anxiety, depressive symptoms, or stress-related ill-health that warrants treatment,
2. be at least 18 years old,
3. have regular access to a device with an Internet connection,
4. be able to read and write in Swedish,
5. have no severe psychiatric disorder that requires specialized psychiatric care, such as psychosis, bipolar disorder, or anorexia nervosa,
6. if on medication with monoamine agonist, have stable dosage in the past month,
7. have no on-going psychological treatment, and
8. provide written informed consent for participation and complete baseline assessment

Exclusion criteria:

As the targeted population in this trial is primary care patients with subsyndromal mental ill-health that do not have a manifest specific common mental disorder, patients will be excluded if they meet diagnostic criteria for an anxiety disorder (social phobia, panic disorder, agoraphobia, general anxiety disorder, or specific phobia), a health anxiety disorder (hypochondriasis or illness anxiety disorder), obsessive-compulsive disorder, depression (depression or dysthymia), or a stress-related disorder (exhaustion disorder, adjustment disorder, or post-traumatic stress disorder). Note that meeting diagnostic criteria for not otherwise specified disorders (e.g., anxiety not otherwise specified), mixed anxiety and depressive disorder, or disorders subsumed under "other" categories is not a reason for exclusion.

Primary outcomes:
measure: Change from baseline in Depression Anxiety Stress Scales-21 (DASS-21) to 10-week, and 1-and 2- year follow-ups
timeFrame: Baseline, weeks 2, 4, 6, 8, 10 (primary endpoint), and 1-and 2-year follow-up
Secondary outcomes:
measure: Change in WHODAS from baseline to 10-week, and 1- and 2-year follow-ups
timeFrame: Baseline, week 10, 1- and 2-year follow-ups
measure: Change in Work Ability Index from baseline to 10-week, and 1- and 2-year follow-ups
timeFrame: Baseline, week 10, 1- and 2-year follow-ups
measure: Change in Brunnsviken Brief Quality of Life Index from baseline to 10-week, and 1- and 2-year follow-ups
timeFrame: Baseline, week 10, 1- and 2-year follow-ups
measure: Change in sickness absence from 1 year before baseline to 1- and 2-year follow-ups
timeFrame: The 1-year period preceding baseline, 1- and 2-year periods after baseline
measure: Change in EPQR-A Neuroticism scale from baseline to 10-week, and 1-and 2-year follow-ups
timeFrame: Baseline, week 10, 1- and 2-year follow-ups
Other outcomes:
measure: Client Satisfaction Questionnaire at 10-week follow-up
timeFrame: 10-week follow-up
measure: Negative Effects Questionnaire at 10-week follow-up
timeFrame: 10-week follow-up
measure: Credibility Scale (C-scale) 2 weeks after baseline
timeFrame: 2 weeks after baseline
measure: Change in EQ5D from baseline to 10-week, and 1- and 2-year follow-up
timeFrame: Baseline, week 10, 1- and 2-year follow-ups
measure: Change in Difficulties in Emotion Regulation Scale-16 from baseline to 10-week, and 1- and 2-year follow-up follow-up
timeFrame: Baseline, weeks 2, 4, 6, 8, 10, and 1-and 2-year follow-up
measure: Change in Brief Experiential Avoidance Questionnaire from baseline to 10-week, and 1- and 2-year follow-up
timeFrame: Baseline, weeks 2, 4, 6, 8, 10, and 1-and 2-year follow-up
measure: Change in TIPI scale Openness to experience from baseline to 10-week follow-up, and 1- and 2-year follow-up
timeFrame: Baseline, weeks 2, 4, 6, 8, 10, and 1-and 2-year follow-up
measure: Rate of healthcare consumption, by type
timeFrame: The 1-year period preceding baseline, 1- and 2-year periods after baseline
measure: Socioeconomic information regarding income type
timeFrame: The 1-year period preceding baseline, 1- and 2-year periods after baseline
measure: Number of participants with prescribed medication
timeFrame: The 1-year period preceding baseline, 1- and 2-year periods after baseline
measure: Clinical Global Impression Severity (CGI-S) at baseline
timeFrame: Baseline
Locations:
city: Gustavsberg
country: Sweden
facility: Region Stockholm, Gustavsberg Primary Care Center
state: Stockholm
Study officials:
affiliation: Region Stockholm and Karolinska Institutet
name: Erik Hedman-Lagerlöf, PhD, professor
role: PRINCIPAL_INVESTIGATOR
References: