TreVar: Predicting Cognitive Behavioral Therapy Outcome Using Moment-to-moment Brain Signal Variability

Sponsor

Karolinska Institutet (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04191811

Collaborator

(none)

150

Enrollment

Location

35.6

Anticipated Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Many psychiatric patients are not sufficiently improved by current interventions. Functional magnetic imaging brain imaging (fMRI) has proven to be a promising method for predicting treatment outcomes in psychiatric treatment. Individuals moment-to-moment variability have not yet been evaluated as a predictor of treatment of three common forms of mental illness: depression, insomnia and health anxiety. The goal is to investigate whether objective measurements of brain function contribute to a better prediction of a patient's success in treatment than experiences and self-reports, e.g., treatment credibility and patients expectations about the treatment. The prediction model will be tested on internet-delivered CBT (iCBT) for depression, insomnia and health anxiety. 50 patients in each diagnostic group are asked for participation before treatment.

Being able to better predict how well a psychiatric treatment will work for an individual has great value from both an economic and a treatment perspective. The findings from this study may contribute to increased knowledge about neurobiological complications in mental illness. In the longer term, it can lead to improved routines and help in clinical decision-making when patients should be recommended treatment.

Condition or Disease	Intervention/Treatment	Phase
Psychiatric Disorder Depression Anxiety Disorders Insomnia	Behavioral: Internet-delivered cognitive behavioral therapy for major depressive disorder Behavioral: Internet-delivered cognitive behavioral therapy for insomnia Behavioral: Internet-delivered cognitive behavioral therapy for health anxiety disorder

Detailed Description

Background: There is extensive evidence that cognitive behavioral therapy (CBT) is an effective method of treating common psychiatric disorders such as depression, health anxiety and insomnia. However, access to CBT is very limited. Furthermore, evidence suggest that internet-delivered CBT (iCBT) is as effective as traditional CBT. However, many psychiatric patients are not sufficiently improved by current interventions. Functional brain imaging has proven to be a promising method for predicting treatment outcomes in psychiatric treatment. Calculations on brain signal variability based on the blood-oxygen-level-dependent, BOLD signal (BOLD-fMRI) is a relatively new technique, shown to accurately predict chronological age and cognitive performance. Preliminary data from the investigators' lab suggest that pre-treatment BOLD-fMRI variability is predictive of CBT outcome in patients with social anxiety disorder.

Objectives: The objective of the study is to investigate whether objective measurements of brain function, in comparison with subjective experiences and self-reports (e.g., rating on treatment credibility and patients expectations about the treatment), contribute to better prediction of treatment outcome. The prediction model will be tested on iCBT for three common forms of mental disorders (depression, insomnia and health anxiety). Furthermore, participants will be compared with healthy controls to better understand neurobiological factors that may contribute to mental illness. Preliminary data from the investigators' lab suggest that BOLD-fMRI variability differs between social anxiety disorder participants and healthy individuals.

Method: A sample of outpatients scheduled for iCBT treatment for depression, insomnia or health anxiety at the Internet Psychiatry Unit will be invited to participate in the study. In addition to clinical participants, a healthy control group will be recruited via advertisement in social media.The length of the iCBT intervention is 12 weeks, during which participants engage in web-based treatment modules in a sequential manner, guided though a digital messaging system by a licensed psychologist who provides support and feedback on progress and assignments.

Measuring instruments: Brain imaging is performed before the patients initiate psychiatric treatment. The brain will be examined with structural and functional magnetic resonance imaging (MRI) using an EPI sequence to capture the BOLD signal (Philips 3-Tesla, 32 channel head-coil).

During the online self-referral process and during clinical intake interview, data on a number of potential predictor variables are collected:

Within the social-demographic domain: age; gender; relationship status (dichotomized as being single or not); level of education rated on a 7-point scale (1 = less than 7-9 years in school; 2 = 7-9 years in school; 3 = incomplete vocational or secondary school; 4 = vocational school; 5 = secondary school; 6 = university, started but not completed studies; 7 = completed university studies); employment status dichotomized as working full-time or not; and having children.
Within the clinical characteristics domain: duration of illness (years since onset), history of psychotropic medication, history of inpatient psychiatric care, history of depression, attempted suicide, currently on medication, and currently on psychotropic medication.
Presence (yes/no) of any comorbid illness is assessed using the the Mini-International Neuropsychiatric Interview (MINI), including panic disorder, agoraphobia, social anxiety disorder, insomnia, health anxiety, mild depressive episode, moderate depressive episode, severe depressive episode, recurrent mild depressive episode, recurrent moderate depressive episode, recurrent severe depressive episode, recurrent depression without current symptoms and dysthymia.
Having a family history of mental illness is assessed prior to treatment, screening for having a family history of dependence / substance abuse, bipolar disorder, depression, minor depression, neuropsychiatric condition, anxiety, panic disorder, psychosis, social anxiety disorder, social anxiety disorder-like symptoms, suicide attempts or suicide completed.
Treatment process factors including perceived treatment credibility measured during the second week in treatment, measured with the Treatment Credibility Scale (TCS) where patients' attitudes to the credibility of the treatment and expectancy regarding treatment effectiveness are rated on a 10-point scale (0 = not at all to 10 = very much). Second, treatment adherence is measured at post-treatment, reflecting the degree of use of the ICBT program operationalised as the total number of activated treatment modules.

Measurements only administered at screening/pre-treatment:

Panic Disorder Severity Scale - Self rated (PDSS-SR; all participants)
Liebowitz Social Anxiety Scale, Self-report (LSAS-SR; all participants)
Social Phobia Inventory (SPIN; all patients)
The Alcohol Use Disorders Identification Test (AUDIT; all participants)
The Drug Use Disorders Identification Test (DUDIT; all participants)
The Adult Self Report Scale (ASRS-V1; all patients)
WHO Disability Assessment Schedule (WHODAS 2.0; all participants)
Metacognitive Beliefs in Health Anxiety (MCQ-HA: health anxiety participants)
Working Alliance Inventory (WAI; health anxiety participants)
General Self-Efficacy scale (S-GSE; insomnia participants)

Behavioural measurements before/while undergoing MRI (all participants):

Positive and Negative Affect Schedule (PANAS)
Affect (valence and arousal). "How much pleasure or discomfort are you feeling right now? (1-9)" and "How calm or upset do you feel right now? (1-9)"
Karolinska Sleepiness Scale (KSS)
Subjective unit of discomfort (SUD): fear and distress (0-100)
Self-rated health (SRH-5)
Short Grit Scale (Grit-S)

Predictors of treatment outcome

Behavioral predictor(s) of treatment outcome:

Questions about desired and expected treatment improvement. These include a) treatment credibility and b) modified PHQ-9, SHAI and ISI questionnaires where the participants' expectation after completed treatment is self-rated for each item as well as participants' desire of improvement on a 0-100 scale for each item.
Ecological momentary assessments (EMA) with repeated sampling of participants' current behaviors and experiences in real time (4 times/day, during approximately 5 days prior to MRI procedure), including sleep problems, sleepiness, depressive symptoms, fear and discomfort. The purpose is to measure different and varied experiences / feelings over time. Variability in experiences will be compared to the participant's variability in brain function to answer the question of whether emotion variability can predict treatment outcomes. The specific EMA questions include the following: PHQ-2, Karolinska Sleepiness Scale (KSS), Item 1 from ISI, Item 1 from SHAI, and subjective units of discomfort (fear and distress).
Social Network Index (SNI)
Emotion categorical ambiguity task

Brain-signal variability predictor(s), as derived from the following BOLD-fMRI experiments (all participants):

Face localizer task
Repetition suppression: faces (neutral, sad, angry, fear), scenes, verbal condition (á 60-90 seconds)
Faces
Scenes
Mooney faces
Retinotopy, i.e., traveling-wave method

Study Design

Study Type:

Observational

Anticipated Enrollment :

150 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Moment-to-moment Neural Variability as a Predictor of Treatment Outcome in Patients With Common Psychiatric Disorders: Major Depressive Disorder, Insomnia and Health Anxiety Disorder

Actual Study Start Date :

Dec 12, 2019

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Depression Internet-delivered CBT 12 weeks of guided internet-delivered CBT for depression.	Behavioral: Internet-delivered cognitive behavioral therapy for major depressive disorder Cognitive behavioral therapy delivered over a period of 12 weeks, guided by a psychologist who provides written feedback on home assignments and questions.
Insomnia Internet-delivered CBT 12 weeks of guided internet-delivered CBT for insomnia.	Behavioral: Internet-delivered cognitive behavioral therapy for insomnia Cognitive behavioral therapy delivered over a period of 12 weeks, guided by a psychologist who provides written feedback on home assignments and questions.
Health Anxiety Internet-delivered CBT 12 weeks of guided internet-delivered CBT for health anxiety.	Behavioral: Internet-delivered cognitive behavioral therapy for health anxiety disorder Cognitive behavioral therapy delivered over a period of 12 weeks, guided by a psychologist who provides written feedback on home assignments and questions.

Arm

Intervention/Treatment

Depression Internet-delivered CBT

12 weeks of guided internet-delivered CBT for depression.

Behavioral: Internet-delivered cognitive behavioral therapy for major depressive disorder

Cognitive behavioral therapy delivered over a period of 12 weeks, guided by a psychologist who provides written feedback on home assignments and questions.

Insomnia Internet-delivered CBT

12 weeks of guided internet-delivered CBT for insomnia.

Behavioral: Internet-delivered cognitive behavioral therapy for insomnia

Cognitive behavioral therapy delivered over a period of 12 weeks, guided by a psychologist who provides written feedback on home assignments and questions.

Health Anxiety Internet-delivered CBT

12 weeks of guided internet-delivered CBT for health anxiety.

Behavioral: Internet-delivered cognitive behavioral therapy for health anxiety disorder

Cognitive behavioral therapy delivered over a period of 12 weeks, guided by a psychologist who provides written feedback on home assignments and questions.

Outcome Measures

Primary Outcome Measures

Change from Baseline Montgomery-Åsberg Depression Rating Scale - Self Assessment (MADRS-S) to Post-treatment [Up to 6 months]
The questionnaire has nine items. Overall score ranges from 0 to 54. Lower scores indicates a better outcome.
Change from Baseline Insomnia Severity Index (ISI) to Post-treatment [Up to 6 months]
The questionnaire has seven items. The overall score ranges from 0 to 28. Lower scores indicates a better outcome.
Change from Baseline Short Health Anxiety Inventory (SHAI) to Post-treatment [Up to 6 months]
The questionnaire has 18 items. The overall score ranges from 0 to 54. Lower scores indicates a better outcome.

Secondary Outcome Measures

Change from Baseline EuroQol 5-dimensions (EQ5D) to Post-treatment [Up to 6 months]
A standardized instrument for measuring generic health status.The questionnaire has five items. The maximum overall score is 1 for the index version and 100 on the VAS scale. Higher scores indicates a better outcome.
Consultation Satisfaction Questionnaire (CSQ-8) to Post-treatment [3 months]
The questionnaire has 8 items. The overall score ranges from 8 to 32. Higher scores indicates a better outcome.
Change from Baseline The Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS) to Post-treatment (insomnia patients) [Up to 3 months]
The questionnaire has 30 items. The overall score ranges from 0 to 300. Lower scores indicates a better outcome.
Change from Baseline Generalized Anxiety Disorder Scale (GAD-7) to Post-treatment (health anxiety patients) [Up to 6 months]
The questionnaire has seven items. The overall score ranges from 0 to 21. Lower scores indicates a better outcome.
Change from Baseline Patient Health Questionnaire-9 (PHQ-9) to Post-treatment (depression and insomnia patients) [Up to 6 months]
The questionnaire has nine items. The overall score ranges from 0 to 27. Lower scores indicates a better outcome.
Change from Baseline The Sleep Problem Acceptance Questionnaire (SPAQ) to Post-treatment (insomnia patients) [Up to 3 months]
The questionnaire has eight items, with scores from 0-6. The overall score ranges from 0-48. A high total score indicates a better outcome, i.e. a high level of acceptance.
Change from Baseline Sleep-Related Behaviours Questionnaire (SRBQ) to Post-treatment (insomnia patients) [Up to 3 months]
The questionnaire has 32 items. The overall score ranges from 32-160. Lower scores indicates a better outcome.
Change from Baseline Trimbos and Institute of Medical Technology Assessment Cost Questionnaire for Psychiatry (TIC-P) to 6 months (all patients) [Up to 6 months]
Measures medical consumption and productivity losses. There is no preset range of minimum-maximum score, since the instrument evaluates productivity losses and reported use of medication. However, estimated costs due to productivity losses and medication consumption suggest that lower values indicates a better outcome.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Meeting DSM-5 criteria for depression, health anxiety or insomnia. Diagnosis and measures of symptom burden and functional level are made through a structured interview, the Mini-International Neuropsychiatric Interview (M.I.N.I.) and self-assessments of symptoms. Healthy controls should not be relevant to psychiatric treatment nor meet criteria for any psychiatric condition according to the M.I.N.I.
Being able to read, write and speak Swedish in order to be able to read the treatment texts and be able to make phone calls.
Having basic computer skills to be able to complete surveys via the Internet and access the treatment platform.

Exclusion Criteria:

Physical or mental illnesses who are either contraindicated for treatment (for example, bipolar disorder that can be exacerbated by treatment) or for other reasons need other treatments (for example, people with severe depression and / or suicide risk).
High alcohol consumption or other ongoing drug use
Answering "yes" to any of the following questions will be excluded for participation:

"Have you or have you had any electrical / battery operated implants in your body? For example, a pacemaker, medication pump, neurostimulator, hearing implant, or other electrical / battery controlled implant?" 2) "Have you done any surgery on the abdomen, chest, heart or brain, eyes, ears? For example, vessel clips, or objects such as screws, heart valve, shunt or prosthesis?" 3) "Do you have or have you had any metallic object in your body?" 4) "If a woman, are you pregnant or breastfeeding?" 5) "Do you undergo dialysis or have kidney dysfunction?" Participants who answer yes to these follow-up questions will be interviewed more closely to determine if MRI security can be guaranteed and whether the MRI signal will have significant disruptions, for example due to dental scaffolding. 1) "If you have any abdominal, thoracic, heart or brain, eyes, ears? Do you have any inoperable object that has ferromagnetic properties?" The patient will be asked to consult his doctor about this.
"If you have a dental rack, what type of dental rack (fixed or removable, metal plates / rails or wire)"?