Face Your Fears: Cognitive Behavioural Virtual Reality Therapy for "Paranoia".

Psychotic Disorders Clinical Trial

— FYF  

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04902066
• Other study ID #: 0134-00066B and ID 148727
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 9, 2021
• Est. completion date: August 2024

Study information

• Verified date: June 2024
• Source: Mental Health Services in the Capital Region, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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, is in progress.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 258
• Est. completion date: August 2024
• Est. primary completion date: March 21, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Delusions
• Mental Disorders
• Paranoid Schizophrenia
• Psychotic Disorders
• Schizophrenia
• Schizophrenia and Related Disorders
• Schizophrenia Prodromal
• Schizophrenia, Paranoid
• Schizotypal Disorder

Intervention

Other:
• Cognitive Behavioural Virtual Reality Therapy.
Cognitive Behavioural Therapy augmented with Virtual Reality.
• Traditional Cognitive Behavioural Therapy
Traditional Cognitive Behavioural Therapy for psychosis.

Locations

Country	Name	City	State
Denmark	Copenhagen Research Center for Mental Health - CORE	Copenhagen	Hellerup

Sponsors (3)

Lead Sponsor	Collaborator
Mental Health Services in the Capital Region, Denmark	Central Denmark Region, Mental Health Services in the North Denmark Region

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CDSS (Calgary Depression Scale for Schizophrenia)	Minimum score: 0 Maximum score: 9*3 = 27. Higher score means worse outcome.	3 and 9 months from inclusion
Other	BNSS (Brief Negative Symptom Scale)	13 items with a score from minimum 0 to maximum 6 for each item. Higher score means worse outcome.	3 and 9 months from inclusion
Other	COGDIS (Cognitive disturbances scale)	Score of 0-6 indicate a range. Minimum score: 0 Maximum score: 9*6 = 54. Higher score means worse outcome. Trait phenomenons are coded with a "7", unknown degree of severly is coded with a "8" and uncertainty whether the symptom is present is coded with a "9".	3 and 9 months from inclusion
Other	SAPS (Scale for the Assesment of Positive symptoms)	Composite total score: Minimum score: 0 Maximum score: 30*5 = 150. Higher score means worse outcome.; Global score: Minimum score: 0 Maximum score: 4*5 = 20. Higher score means worse outcome.	3 and 9 months from inclusion
Other	Trustworthiness Scale	Minimum score: -3*42=-126 Maximun score: +3*42=126. Higher positive score means better outcome. Higher negative score means worse outcome.	3 and 9 months from inclusion
Other	DACOBS (Davos Assessment of the Cognitive Biases Scale)	Total score: Minimum score: 1*42=42. Maximum score:7*42=294. Higher score means worse outcome.; Subscales of: Jumping to conclusions bias: Item 3+8+16+18+25+30 Belief Inflexibility bias: Item 13+15+26+34+38+41 Attention for Threat bias: Item 1+2+6+10+20+37 External Attribution bias: Item 7+12+17+22+24+29; Social Cognition problems: Item 4+9+11+14+19+39 Subjective Cognitive problems: Item 5+21+28+32+36+40; Safety behaviors: Item 23+27+31+33+35+42	3 and 9 months from inclusion
Other	SIDAS (Suicidal Ideation Attributes Scale)	Minimum score: 0. Maximum score: 50. Item 2 has a reverse score. Higher score means worse outcome.	3 and 9 months from inclusion
Other	BCSS (The Brief Core Schema Scales: Beliefs about self and others)	Items with negative belief of self and others: Minimum score: 0. Maximum score: 2*6*4= 48. Higher score means worse outcome.; Items with Positive belief of self and others: Minimum score: 0. Maximum score: 2*6*4= 48. Higher score means better outcome.	3 and 9 months from inclusion
Other	SSPA (Social Skills Performance Assessment)	Scene I: Minimum score: 1*8=8. Maximum score: 5*8:40. Higher score means better outcome.; Scene II: Minimum score: 1*9=9. Maximum score: 5*9:45. Higher score means better outcome.	3 and 9 months from inclusion
Other	TALE (Trauma And Life Events checklist)		Baseline measure
Other	IBT (Intentionality Bias Task)		3 and 9 months from inclusion
Other	(R-GPTS) Revised Green Paranoid Thought Scale	Minimum total score: 0. Maximum total score: 4*18=72. Part A (Ideas of social reference) minimum score: 0 and maximum score: 4*8=32. Part B (Ideas of persecution) minimum score 0 and maximum score: 4*10=40. Part B score = or > 18 are assumed to be threshold for development of delusion. Higher score means worse outcome.	3 and 9 months from inclusion
Other	GSE (General Self Efficacy Scale)	Minimum score: 1*10=10. Maximum score: 4*10=40. Higher score means better outcome.	3 and 9 months from inclusion
Other	Big-5 (personality traits)	5 spectrums of personality traits assessed with 5 items each.; Minimum score for each personality trait: Minimum score: 1*5=5. Maximum score: 5*5=25; Certain items have reverse scores.	3 and 9 months from inclusion
Other	EQ-5D-5L (EuroQOL five dimensions questionnaire)	Scoring the descriptive system: Minimum score: 1-1-1-1-1. Maximum score: 5-5-5-5-5. Higher score means worse outcome.; Scoring the VAS: Minimum score: 0. Maximum score: 100. Higher score means better outcome.	3 and 9 months from inclusion
Other	WHO (World Health Organization 5)	Minimum score: 0. Maximum score: 5*5*4=100. Higher score means better outcome.	3 and 9 months from inclusion
Other	CSQ (Client Satisfaction Questionnaire)		3 months follow-up
Other	SFS (The Social Functioning Scale)	Minimum raw score: 0. Maximum raw score: 15+9+39+45+66+39+19=223. Higher score means better outcome.	3 and 9 months from inclusion
Primary	(GPTS) Green Paranoid Thought Scale Part B: Ideas of persecution.	The primary outcome is level of ideas of persecution measured with Green Paranoid Thought Scale at cessation of treatment at 3-months. The Green Paranoid Thought Scale has displayed good reliability and validity in patients with psychosis, displaying paranoid, persecutory delusions, and has also been used in patients at-risk for psychosis showing subthreshold psychotic symptoms.; Minimum total score: 32. Maximum total score: 160. Part A (Ideas of social reference) minimum score: 16 and maximum score: 80. Part B (ideas of persecution) minimum score 16 and maximum score: 80. Part B score = or > 45 are assumed to be threshold for development of persecutory delusion.; Higher score means worse outcome.	3 months from inclusion
Secondary	SIAS (Social Interaction Anxiety Scale)	Minimum score: 0 Maximum score: 20*4=80. Item 5,9 and 11 have reverse score. Higher score means worse outcome.	3 and 9 months from inclusion
Secondary	SBQ (Safety Behaviour Questionnaire)	Minimum score: 0. Maximum score is in theory unlimited depending on the number of identified, specific safety behaviours.	3 and 9 months from inclusion
Secondary	PSP (Personal and Social Performance Scale)	Minimum score: 1 Maximum score: 100. Higher score means better outcome.	3 and 9 months from inclusion
Secondary	CANTAB ERT (Emotion Recognition Task)		3 and 9 months from inclusion
Secondary	(GPTS) Green Paranoid Thought Scale Part A: Ideas of social reference	Minimum total score: 32. Maximum total score: 160. Part A (Ideas of social reference) minimum score: 16 and maximum score: 80. Part B (Ideas of persecution) minimum score 16 and maximum score: 80. Part B score = or > 45 are assumed to be threshold for development of delusion. Higher score means worse outcome.	3 and 9 months from inclusion
Secondary	(GPTS) Green Paranoid Thought Scale Part B: Ideas of persecution	Minimum total score: 32. Maximum total score: 160. Part A (Ideas of social reference) minimum score: 16 and maximum score: 80. Part B (Ideas of persecution) minimum score 16 and maximum score: 80. Part B score = or > 45 are assumed to be threshold for development of delusion. Higher score means worse outcome.	9 months from inclusion