Schizophrenia DisordersVIPNCT06835556
Volatility in Paranoia (VIP) Trial: An RCT of Changes in Volatility With Psychotherapy
A study testing Cognitive Behavioral Therapy and TAU in people with Schizophrenia Disorders, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia Disorders
- What is being tested?
- Cognitive Behavioral Therapy and TAU
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2025to 1 Feb 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
Julia Sheffield, PhD, 615-343-3839, julia.sheffield@vumc.org
About this study
Official title: 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:
- do prior expectations about environmental volatility reduce following effective psychotherapeutic treatment of delusions?
- does corresponding brain activity related to volatility change with effective treatment of delusions?
Participants will:
- engage in CBTp or TAU + phone check-ins for 16 weeks
- complete assessments at 4 timepoints over the course of 6 months
- complete an MRI when possible
- Conditions
- Schizophrenia Disorders
- Being tested
- Cognitive Behavioral Therapy, TAU
- Keywords
- Schizophrenia, Delusion, Paranoia, Psychotherapy, Beliefs, Volatility, Cognitive Behavioral Therapy, CBTp, Psychosis
- Medical subject headings
- Schizophrenia, Delusions, Paranoid Disorders, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive Behavioral TherapyBehavioural
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.
TAUBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Behavioral: TAU |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline to 16 weeks
Volatility Expectations - During Stable3 Task
Measured: Change from baseline
Scale of Unpredictability Beliefs
Measured: Change from baseline
Secondary outcomes (25)
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
Measured: 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
Measured: 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.
Measured: Baseline to 16 weeks
BOLD activation changes during PRL task, pre/post treatment - whole brain analysis
Measured: Baseline to 16 weeks
PSYRATS Hallucinations
Measured: Change from baseline
Kamin Blocking
Measured: Change from baseline
Social Hallucinations - Chasing
Measured: Change from baseline
Minnesota Trust Game
Measured: Change from baseline
r-GPTS
Measured: Change from baseline
DWQ
Measured: Change from baseline
BDI-II
Measured: Change from baseline
O-AS
Measured: Change from baseline
Positive Thoughts Scale
Measured: Change from baseline
Guilt and Shame Experiences Scale
Measured: Change from baseline
O-CDQ
Measured: Change from baseline
Insomnia Severity Index
Measured: Change from baseline
PCL-5
Measured: Change from baseline
CEFSA
Measured: Change from baseline
DERS-16
Measured: Change from baseline
Intolerance of Uncertainty
Measured: Change from baseline
LSAS
Measured: Change from baseline
LSNS-6
Measured: Change from baseline
CHOICE
Measured: Change from baseline
WEMWBS
Measured: Change from baseline
MCQ-36
Measured: Change from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2025
- Study start15 Jan 2025
- Primary completion3 Sep 2029 (estimated)
- Study completion1 Feb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Schizophrenia DisordersStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Julia Sheffield, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06835556
- Sponsor's protocol ID
- 240788
- Other IDs
- R01MH137024
- Acronym
- VIP
- Status last verified
- Sep 2026
- First submitted
- 12 Feb 2025
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Testing the Role of Belief Updating in Persecutory Delusions
- ClinicalTrials.gov ID
- NCT06835556
- Acronym / sponsor ID
- VIP / 240788
- Conditions
- Schizophrenia Disorders
- Keywords
- Schizophrenia, Delusion, Paranoia, Psychotherapy, Beliefs, Volatility, Cognitive Behavioral Therapy, CBTp
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 15 Jan 2025 (actual)
- Primary completion
- 3 Sep 2029 (estimated)
- Study completion
- 1 Feb 2030 (estimated)
- First posted
- 19 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- do prior expectations about environmental volatility reduce following effective psychotherapeutic treatment of delusions?
- does corresponding brain activity related to volatility change with effective treatment of delusions?
Participants will:
- engage in CBTp or TAU + phone check-ins for 16 weeks
- complete assessments at 4 timepoints over the course of 6 months
- complete an MRI when possible
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CBTp | Experimental | Behavioral: Cognitive Behavioral TherapyWeekly individual psychotherapy targeting specific maintenance factors of paranoia (worry, anomalous experiences, self-confidence, and safety behaviors), tailored to the participant's experience |
| TAU + Phone Check-In | Active comparator | Behavioral: TAUParticipants 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive Behavioral TherapyIndividuals 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. | Behavioural | CBTp |
| TAUIndividuals 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. | Behavioural | TAU + Phone Check-In |
Primary outcome
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
Volatility Expectations - During Stable3 Task
Time frame: Change from baseline
Scale of Unpredictability Beliefs
Time frame: Change from baseline
25 secondary outcomes
Change in PANSS P1 Item
Time frame: Baseline to 16 weeks
Change in PANSS P6 Item
Time frame: Baseline to 16 weeks
Change in meta-volatility learning rate (omega3)
Time frame: Baseline to 16 weeks
BOLD activation changes during PRL task, pre/post treatment - whole brain analysis
Time frame: Baseline to 16 weeks
PSYRATS Hallucinations
Time frame: Change from baseline
Kamin Blocking
Time frame: Change from baseline
Social Hallucinations - Chasing
Time frame: Change from baseline
Minnesota Trust Game
Time frame: Change from baseline
r-GPTS
Time frame: Change from baseline
DWQ
Time frame: Change from baseline
BDI-II
Time frame: Change from baseline
O-AS
Time frame: Change from baseline
Positive Thoughts Scale
Time frame: Change from baseline
Guilt and Shame Experiences Scale
Time frame: Change from baseline
O-CDQ
Time frame: Change from baseline
Insomnia Severity Index
Time frame: Change from baseline
PCL-5
Time frame: Change from baseline
CEFSA
Time frame: Change from baseline
DERS-16
Time frame: Change from baseline
Intolerance of Uncertainty
Time frame: Change from baseline
LSAS
Time frame: Change from baseline
LSNS-6
Time frame: Change from baseline
CHOICE
Time frame: Change from baseline
WEMWBS
Time frame: Change from baseline
MCQ-36
Time frame: Change from baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive Behavioral Therapy and TAU in people with Schizophrenia Disorders, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Julia Sheffield, PhD (615-343-3839, julia.sheffield@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in prior expectations of volatility (mu3) (time frame: Baseline to 16 weeks). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026.