Recruiting

Psychotherapy

Sponsor:

Vanderbilt University Medical Center

Code:

NCT06835556

Conditions

Schizophrenia Disorders

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Cognitive Behavioral Therapy

TAU

Study Details

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

Conditions

Schizophrenia Disorders

Study ID

NCT06835556

Start date

Jan 15, 2025

Status verified date

May, 2026

Completion date

Feb 1, 2030

Anticipated

Primary completion date

Sep 3, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

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

Enrollment

120 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

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

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

Interventions

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.

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 measure

  • Change in prior expectations of volatility (mu3) [ Time Frame: Baseline to 16 weeks ]
  • Change in unexpected uncertainty (kappa) [ Time Frame: Baseline to 16 weeks ]
  • Change in psychotic Symptom Rating Scale (PSYRATS)- Belief Subscale Total [ Time Frame: Baseline to 16 weeks ]
  • Change in PANSS Positive Symptoms - Total [ Time Frame: Baseline to 16 weeks ]
  • BOLD activation change during PRL task, pre/post treatment - prefrontal cortex [ Time Frame: Baseline to 16 weeks ]
  • BOLD activation change pre/post treatment - striatum [ Time Frame: Baseline to 16 weeks ]
  • BOLD activation change during PRL task, pre/post treatment - locus coeruleus [ Time Frame: Baseline to 16 weeks ]
  • Task-based functional connectivity changes during PRL task, pre/post treatment - prefrontal cortex to striatum [ Time Frame: Baseline to 16 weeks ]

Central Contacts and Locations

Central contacts

Julia Sheffield, PhD

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

Locations

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37212

Contacts

Julia Sheffield, PhD

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

More Information

Sponsor

Vanderbilt University Medical Center

Last update posted

May 6, 2026

Last verified

May, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Vanderbilt University Medical Center on 2026-05-06.