NCT06835556 · Vanderbilt University Medical Center
Volatility in Paranoia (VIP) Trial: An RCT of Changes in Volatility With Psychotherapy
(VIP)
What this study is about
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.
View original scientific description
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.
Interventions
BEHAVIORAL
Cognitive Behavioral Therapy
Individuals will be assessed for which psychological factors are maintaining paranoia in their daily lives. They will collaboratively identify one maintenance factor to focus on (e.g. worry, anomalous experience, self-confidence, PTSD) for 8 weeks of individual therapy. Then, all participants will transition to 8 weeks of individual therapy focused on dropping safety behaviors and re-engaging in everyday life.
BEHAVIORAL
TAU
Individuals will continue treatment as usual (TAU). In addition they will have contact with a study therapist weekly via phone to provide information on what treatment they received. Phone check-ins will last approximately 5-10 minutes.
Primary outcome measures
Change in prior expectations of volatility (mu3)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline to 16 weeks
Functional connectivity during the PRL task will be quantified between the dlPFC and striatum
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
Where
- Nashville, Tennessee
Collaborators
National Institute of Mental Health (NIMH)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 6, 2026 · Source of record for eligibility and locations