Clinical trial NCT06835556: Volatility in Paranoia (VIP) Trial: An RCT of Changes in Volatility With Psychotherapy
Official title: Testing the Role of Belief Updating in Persecutory Delusions
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Schizophrenia Disorders
Keywords: Schizophrenia
Delusion
Paranoia
Psychotherapy
Beliefs
Volatility
Cognitive Behavioral Therapy
CBTp
Psychosis
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2025-02-19
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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

Primary outcomes:
measure: Change in prior expectations of volatility (mu3)
timeFrame: Baseline to 16 weeks
measure: Change in unexpected uncertainty (kappa)
timeFrame: Baseline to 16 weeks
measure: Change in psychotic Symptom Rating Scale (PSYRATS)- Belief Subscale Total
timeFrame: Baseline to 16 weeks
measure: Change in PANSS Positive Symptoms - Total
timeFrame: Baseline to 16 weeks
measure: BOLD activation change during PRL task, pre/post treatment - prefrontal cortex
timeFrame: Baseline to 16 weeks
measure: BOLD activation change pre/post treatment - striatum
timeFrame: Baseline to 16 weeks
measure: BOLD activation change during PRL task, pre/post treatment - locus coeruleus
timeFrame: Baseline to 16 weeks
measure: Task-based functional connectivity changes during PRL task, pre/post treatment - prefrontal cortex to striatum
timeFrame: Baseline to 16 weeks
Secondary outcomes:
measure: Change in PANSS P1 Item
timeFrame: Baseline to 16 weeks
measure: Change in PANSS P6 Item
timeFrame: Baseline to 16 weeks
measure: Change in meta-volatility learning rate (omega3)
timeFrame: Baseline to 16 weeks
measure: BOLD activation changes during PRL task, pre/post treatment - whole brain analysis
timeFrame: Baseline to 16 weeks
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
References: