Clinical trial NCT04902066: Face Your Fears: Cognitive Behavioural Virtual Reality Therapy for "Paranoia".
Official title: Face Your Fears: an Assessor-blinded, RCT Evaluating the Effectiveness of Cognitive Behavioural Virtual Reality Therapy Versus Cognitive Behavioural Therapy in Patients with Schizophrenia Spectrum Disorders.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Paranoid Schizophrenia
Schizophrenia and Related Disorders
Schizophrenia Prodromal
Schizotypal Disorder
Paranoid Ideation
Paranoid Delusion
Ideas of Reference
Psychosis Paranoid
Psychotic Disorders
Psychotic Paranoia
Psychotic; Disorder, Delusional
Lead sponsor: Mental Health Services in the Capital Region, Denmark
Sponsor class: OTHER
Collaborators: name: Central Denmark Region
name: Mental Health Services in the North Denmark Region
First posted: 2021-05-26
Enrollment: 254
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomised, assessor-blinded parallel-groups superiority clinical trial.
Primary purpose: TREATMENT

Brief summary: The study is a randomised, assessor-blinded parallel-groups superiority clinical trial fulfilling the CONSORT criteria for non-pharmacological treatment. A total of 256 patients will be allocated to either Cognitive Behavioural Virtual Reality Therapy plus treatment as usual, versus traditional CBT for psychosis plus treatment as usual. All participants will be assessed at baseline and 3- and 9 months post baseline. A stratified block-randomisation with concealed randomisation sequence will be conducted. Independent assessors blinded to the treatment will evaluate outcome. Analysis of outcome will be carried out with the intention to treat principles.

Detailed description: Ideas of reference and ideas of persecution are among the most frequent symptoms in psychotic disorders, and they hinder patients in conducting daily activities such as leaving the home or using public transportation - as well as inflicting immensely on their quality of life. The social avoidance caused by these symptoms does not improve with antipsychotic mediation. Cognitive behavioural therapy (CBT) for psychosis has demonstrated beneficial effect on psychotic symptoms, but the average effect sizes are in the small to moderate range, and training and resource requirements mean that, in practice, therapy is not delivered to all those who might benefit. Hence, there is considerable interest in the development of novel therapies that draw on the principles of cognitive behavioural therapy for psychosis, but which are shorter, more effective, and are capable of being delivered by a wider workforce. Augmenting CBT with virtual reality exposure has the possibility of creating artificial experiences in real time, that make the user feel immersed and able to interact as if it was the real world. Additionally, virtual reality therapy allows for personalization of the therapy to match the specific social challenges of each patient. Preliminary findings suggest virtual reality exposure to lead to faster symptom reduction than traditional therapy. While the potential beneficial effects of virtual reality exposure to psychotic, and sub-threshold psychotic symptoms, such as ideas of reference and ideas of persecution, are evident and virtual reality therapies are promising in general, the research field is in an urgent need of evidence on the effectiveness of virtual reality therapy in patients with schizophrenia spectrum disorders. The proposed trial is hitherto the largest trial in the world to evaluate the effectiveness of cognitive behavioural virtual reality therapy (CBT-VR) compared to traditional CBT. The investigators expect to find CBT-VR to be more beneficial in reducing ideas of reference and ideas of persecution in patients with schizophrenia spectrum disorders. Additionally, the investigators expect it to result in improved depressive, anxiety-, and negative symptoms, as well as improved social cognition and psychosocial functioning and quality of life in patients with schizophrenia spectrum disorders. The target group in the trial also encompass patients with schizotypal disorder (often young adults), showing subthreshold psychotic symptoms (e.g. ideas of reference), that are at increased risk of developing manifest psychosis. The CBT-VR may show efficacy in preventing progression to an overt psychotic state in these patients. Hence, there is a great potential for CBT-VR in the treatment of patients with psychosis and sub-threshold psychosis, but studies are needed to establish evidence for the treatment. If the results of the current trial are positive, the manualised treatment can easily be implemented in clinical practise.

Note:

When the trial was initiated, the original primary outcome was ideas of persecution, measured with part B in Green Paranoid Thought Scale (GPTS) while ideas of social reference, measured with part A in Green Paranoid Thought Scale, was listed as a secondary outcome in the trial protocol, here on Clinicaltrials.gov and in the approval from the Committee on Health Research Ethics of the Capital Region Denmark.

During our trial, our impressions in the clinical assessments were, that ideas of social reference seem to be a more appropriate primary outcome due to our population including people diagnosed with schizotypal disorders along with participants with manifest psychotic disorders.

We observed that participants with schizotypal disorders experiencing ideas of social reference, that are more attenuated paranoid ideations, would often receive a low score on the GPTS part B. Therefore, listing GPTS part B as primary outcome would hypothetically only reflect the symptom level of part of the study population (patients with manifest psychosis), while not fully comprising the symptom level, and potential for change, found in the population of patients with schizotypal disorder. ''

As of February, 23 2022, 10 months into the trial, where 79 participants out of 256 were included and had participated in baseline assessments, we decided after thorough consideration to exchange our primary outcome, GPTS part B, ideas of persecution, with our secondary outcome, GPTS part A, ideas of social reference, as this was intended to capture the symptom level in the total study population.

The exchange did not affect participation in our trial or the informed consent. Intervention in both groups and measurements were unchanged. The two outcomes constitute together GPTS and the unifying concept we attempt to treat, namely paranoid ideations. As this is a blinded, methodologically sound trial, we had not (and still have not throughout the study period) access to preliminary data and therefore no knowledge of the distribution of our two intervention groups nor the potential effect of the intervention.

The power calculation remains unchanged irrespective of the selection of primary outcome. (Ideas of persecution: relevant difference 6.0, SD 17.9, N=128\*2, power= 80%). Due to the notions mentioned above, we did not find any reasons for ethical implications of the change of primary outcome - as we also were fully transparent with this change of outcome here on Clinicaltrials.gov.

We therefore assumed that our ethical committee would approve of this change. However, on September 3 2022 we received a rejection from the Committee on Health Research Ethics of the Capital Region Denmark on changing outcomes, on the invariable grounds that the trial is commenced. This means that it is necessary to keep ideas of persecution, part B in Green Paranoid Thought Scale, as our primary outcome and keep ideas of social reference, part A in Green Paranoid Thought Scale as a secondary outcome.

A design paper was published while we had ideas of social reference, part A in Green Paranoid Thought Scale, as a primary outcome. An Update, informing about this significant change in the form of changing back to the originally, approved, primary outcome, has been published.

Eligibility criteria: Inclusion Criteria:

1. Age 18 - years
2. Ability to give informed consent
3. A schizophrenia spectrum disorder (ICD-10 code: F20 -F29)
4. Green Paranoid Thought Scale total score ≥ 40

Exclusion Criteria:

1. Rejecting informed consent
2. A diagnosis of organic brain disease
3. IQ of 70 or lower (known mental retardation as assessed by medical record)
4. A command of spoken Danish or English inadequate for engaging in therapy
5. Inability to tolerate the assessment process

Primary outcomes:
measure: (GPTS) Green Paranoid Thought Scale Part B: Ideas of persecution.
timeFrame: 3 months from inclusion
Secondary outcomes:
measure: SIAS (Social Interaction Anxiety Scale)
timeFrame: 3 and 9 months from inclusion
measure: SBQ (Safety Behaviour Questionnaire)
timeFrame: 3 and 9 months from inclusion
measure: PSP (Personal and Social Performance Scale)
timeFrame: 3 and 9 months from inclusion
measure: CANTAB ERT (Emotion Recognition Task)
timeFrame: 3 and 9 months from inclusion
measure: (GPTS) Green Paranoid Thought Scale Part A: Ideas of social reference
timeFrame: 3 and 9 months from inclusion
measure: (GPTS) Green Paranoid Thought Scale Part B: Ideas of persecution
timeFrame: 9 months from inclusion
Other outcomes:
measure: CDSS (Calgary Depression Scale for Schizophrenia)
timeFrame: 3 and 9 months from inclusion
measure: BNSS (Brief Negative Symptom Scale)
timeFrame: 3 and 9 months from inclusion
measure: COGDIS (Cognitive disturbances scale)
timeFrame: 3 and 9 months from inclusion
measure: SAPS (Scale for the Assesment of Positive symptoms)
timeFrame: 3 and 9 months from inclusion
measure: Trustworthiness Scale
timeFrame: 3 and 9 months from inclusion
measure: DACOBS (Davos Assessment of the Cognitive Biases Scale)
timeFrame: 3 and 9 months from inclusion
measure: SIDAS (Suicidal Ideation Attributes Scale)
timeFrame: 3 and 9 months from inclusion
measure: BCSS (The Brief Core Schema Scales: Beliefs about self and others)
timeFrame: 3 and 9 months from inclusion
measure: SSPA (Social Skills Performance Assessment)
timeFrame: 3 and 9 months from inclusion
measure: TALE (Trauma And Life Events checklist)
timeFrame: Baseline measure
measure: IBT (Intentionality Bias Task)
timeFrame: 3 and 9 months from inclusion
measure: (R-GPTS) Revised Green Paranoid Thought Scale
timeFrame: 3 and 9 months from inclusion
measure: GSE (General Self Efficacy Scale)
timeFrame: 3 and 9 months from inclusion
measure: Big-5 (personality traits)
timeFrame: 3 and 9 months from inclusion
measure: EQ-5D-5L (EuroQOL five dimensions questionnaire)
timeFrame: 3 and 9 months from inclusion
measure: WHO (World Health Organization 5)
timeFrame: 3 and 9 months from inclusion
measure: CSQ (Client Satisfaction Questionnaire)
timeFrame: 3 months follow-up
measure: SFS (The Social Functioning Scale)
timeFrame: 3 and 9 months from inclusion
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen Research Center for Mental Health - CORE
state: Hellerup
Study officials:
References:
citation: Jeppesen UN, Due AS, Mariegaard L, Pinkham A, Vos M, Veling W, Nordentoft M, Glenthoj LB. Face Your Fears: Virtual reality-based cognitive behavioral therapy (VR-CBT) versus standard CBT for paranoid ideations in patients with schizophrenia spectrum disorders: a randomized clinical trial. Trials. 2022 Aug 15;23(1):658. doi: 10.1186/s13063-022-06614-0.