Volatility in Paranoia (VIP) Trial: An RCT of Changes in Volatility With Psychotherapy

Not Applicable

Recruiting

• Conditions: Schizophrenia Disorders

• Registration Number: NCT06835556
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

The goal of this clinical trial is to learn whether learning and belief updating change in response to the treatment of persecutory delusions, in individuals with schizophrenia-spectrum disorders.

The main questions are:

1. do prior expectations about environmental volatility reduce following effective psychotherapeutic treatment of delusions?

2. does corresponding brain activity related to volatility change with effective treatment of delusions?

Participants will:

1. engage in CBTp or TAU + phone check-ins for 16 weeks

2. complete assessments at 4 timepoints over the course of 6 months

3. complete an MRI when possible

Detailed Description

Not available

Study Timeline

• Study Start: 2025-01-15
• Status Verified: 2025-02
• Study First Submitted: 2025-02-12
• Study First Submitted QC: 2025-02-12
• Study First Posted: 2025-02-19
• Last Update Submitted: 2025-05-05
• Last Update Posted: 2025-05-06
• Primary Completion: 2029-09-03
• Study Completion: 2030-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Men and women age 18 - 65.
• Communicative in English.
• Premorbid IQ >79 (WTAR)
• Provide voluntary, written informed consent.
• Stable medication regimen over at least the past two weeks, including the use of either an oral or intramuscular administration of an antipsychotic medication.
• Diagnosis of a non-affective psychotic disorder (e.g. schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder)
• A persecutory delusion scoring at least a 3 on the conviction scale of the Psychotic Symptoms Rating Scale (PSYRATS) that had persisted for at least two months and that was not considered the direct result of substance use.

Exclusion Criteria

• Serious medical or neurological illness known to interfere with cognitive functioning (uncontrolled/unstable diabetes, uncontrolled hypothyroidism, Cushing's disease, Lupus, any demyelinating disease such as Multiple Sclerosis, HIV infection, CNS infection, unstable heart disease, active hepatitis, other significant endocrine condition, any cancer involving the CNS/brain, any uncorrected vision problems, tardive dyskinesia).
• History of severe head trauma with loss of consciousness >30 minutes.
• Primary diagnosis of alcohol or substance use disorder or personality disorder

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in prior expectations of volatility (mu3)	Baseline to 16 weeks	Reversal learning data will be collected from a 3-option probabilistic reversal learning task. This data will be analyzed using a computational model that estimates the prior expectations of environmental volatility. That parameter, in many models, is Mu3.
Change in unexpected uncertainty (kappa)	Baseline to 16 weeks	Reversal learning data will be collected from a 3-option probabilistic reversal learning task. This data will be analyzed using a computational model that estimates the unexpected uncertainty, sometimes also referred to as sensitivity to volatility.
Change in psychotic Symptom Rating Scale (PSYRATS)- Belief Subscale Total	Baseline to 16 weeks	The PSYRATS is a interview-assisted assessment measuring the severity of a delusional belief. Total scores range from 0-24 with high scores indicating more severe delusion; 6 questions, 0-4 scale for each item
Change in PANSS Positive Symptoms - Total	Baseline to 16 weeks	The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The positive symptom total score is the sum of the Positive Symptom items
BOLD activation change during PRL task, pre/post treatment - prefrontal cortex	Baseline to 16 weeks	functional MRI will be used to collect BOLD activation data during the PRL reversal learning task. The investigators expect changes in activation following treatment, particularly in the CBTp group
BOLD activation change pre/post treatment - striatum	Baseline to 16 weeks	functional MRI will be used to collect BOLD activation data during the PRL reversal learning task. The investigators expect changes in activation following treatment, particularly in the CBTp group
BOLD activation change during PRL task, pre/post treatment - locus coeruleus	Baseline to 16 weeks	functional MRI will be used to collect BOLD activation data during the PRL reversal learning task. The investigators expect changes in activation following treatment, particularly in the CBTp group
Task-based functional connectivity changes during PRL task, pre/post treatment - prefrontal cortex to striatum	Baseline to 16 weeks	Functional connectivity during the PRL task will be quantified between the dlPFC and striatum

Secondary Outcome Measures

Name	Time	Method
Change in PANSS P1 Item	Baseline to 16 weeks	The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. P1 is the first item on the scale, representing delusion severity
Change in PANSS P6 Item	Baseline to 16 weeks	The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. P6 is the item on the scale assessing severity of paranoia/suspiciousness
Change in meta-volatility learning rate (omega3)	Baseline to 16 weeks	Reversal learning data will be collected from a 3-option probabilistic reversal learning task. This data will be analyzed using a computational model that estimates the meta-volatility.
BOLD activation changes during PRL task, pre/post treatment - whole brain analysis	Baseline to 16 weeks

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States