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

NCT06835556 | Recruiting

• 2 other identifiers: 240788R01MH137024
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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. 1.do prior expectations about environmental volatility reduce following effective psychotherapeutic treatment of delusions?
2. 2.does corresponding brain activity related to volatility change with effective treatment of delusions?
3. 3.engage in CBTp or TAU + phone check-ins for 16 weeks
4. 4.complete assessments at 4 timepoints over the course of 6 months
5. 5.complete an MRI when possible

Conditions

Schizophrenia Disorders

Keywords

Schizophrenia; Delusion; Paranoia; Psychotherapy; Beliefs; Volatility; Cognitive Behavioral Therapy; CBTp; Psychosis

Outcome Measures

Primary Outcomes (8)

• Change in prior expectations of volatility (mu3)

  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.

  Baseline to 16 weeks

• Change in unexpected uncertainty (kappa)

  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.

  Baseline to 16 weeks

• Change in psychotic Symptom Rating Scale (PSYRATS)- Belief Subscale Total

  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

  Baseline to 16 weeks

• Change in PANSS Positive Symptoms - Total

  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

  Baseline to 16 weeks

• BOLD activation change during PRL task, pre/post treatment - prefrontal cortex

  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

  Baseline to 16 weeks

• BOLD activation change pre/post treatment - striatum

  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

  Baseline to 16 weeks

• BOLD activation change during PRL task, pre/post treatment - locus coeruleus

  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

  Baseline to 16 weeks

• Task-based functional connectivity changes during PRL task, pre/post treatment - prefrontal cortex to striatum

  Functional connectivity during the PRL task will be quantified between the dlPFC and striatum

  Baseline to 16 weeks

Secondary Outcomes (4)

• Change in PANSS P1 Item

  Baseline to 16 weeks

• Change in PANSS P6 Item

  Baseline to 16 weeks

• Change in meta-volatility learning rate (omega3)

  Baseline to 16 weeks

• BOLD activation changes during PRL task, pre/post treatment - whole brain analysis

  Baseline to 16 weeks

Study Arms (2)

CBTp

EXPERIMENTAL

Weekly individual psychotherapy targeting specific maintenance factors of paranoia (worry, anomalous experiences, self-confidence, and safety behaviors), tailored to the participant's experience

Behavioral: Cognitive Behavioral Therapy

TAU + Phone Check-In

ACTIVE COMPARATOR

Participants will continue with their regular care (treatment as usual (TAU)) without interference from the study team. In addition to TAU, a study therapist will call them weekly to review what treatment the participants have engaged in. Phone calls will last approximately 5-10 minutes

Behavioral: TAU

Interventions

Cognitive Behavioral Therapy BEHAVIORAL

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.

CBTp

TAU BEHAVIORAL

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.

TAU + Phone Check-In

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Delusions; Paranoid Disorders; Psychotic Disorders

Interventions

Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Central Study Contacts

Julia Sheffield, PhD

CONTACT

615-343-3839; julia.sheffield@vumc.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 12, 2025
• First Posted: February 19, 2025
• Study Start: January 15, 2025
• Primary Completion (Estimated): September 3, 2029
• Study Completion (Estimated): February 1, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

US (1)