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

Testing the Role of Belief Updating in Persecutory Delusions

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

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia Disorders
• Intervention / Treatment: Behavioral: Cognitive Behavioral Therapy; Behavioral: TAU

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julia Sheffield, PhD; Phone Number: 615-343-3839; Email: julia.sheffield@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Julia Sheffield, PhD; Phone Number: 615-343-3839; Email: julia.sheffield@vumc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CBTp; 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; 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.
Active Comparator: TAU + Phone Check-In; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD activation changes during PRL task, pre/post treatment - whole brain analysis		Baseline to 16 weeks
Change in PANSS P1 Item	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	Baseline to 16 weeks
Change in PANSS P6 Item	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	Baseline to 16 weeks
Change in meta-volatility learning rate (omega3)	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.	Baseline to 16 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Institute of Mental Health (NIMH)

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2025
• Primary Completion (Estimated): September 3, 2029
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: February 12, 2025
• First Submitted That Met QC Criteria: February 12, 2025
• First Posted (Actual): February 19, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Schizophrenia; Psychosis; Cognitive Behavioral Therapy; Psychotherapy; Beliefs; Paranoia; CBTp; Delusion; Volatility
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Schizophrenia; Psychotic Disorders; Delusions; Paranoid Disorders; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Cognitive Behavioral Therapy
• Other Study ID Numbers: 240788; R01MH137024 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No