NCT04366518 · Yale University
Toward a Computationally-Informed, Personalized Treatment for Hallucinations
What this study is about
Auditory hallucinations are among the most distressing aspects of psychotic illness, and between 10 and 30% of people with hallucinations do not respond to antipsychotic medications. The authors have used computational modeling of behavior to link brain activity to development of auditory hallucinations in the hope of guiding new treatment development.
View original scientific description
Auditory hallucinations are among the most distressing aspects of psychotic illness, and between 10 and 30% of people with hallucinations do not respond to antipsychotic medications. The authors have used computational modeling of behavior to link brain activity to development of auditory hallucinations in the hope of guiding new treatment development. The proposed studies take the first step toward individualized treatment approaches to hallucinations by attempting causal, pharmacological manipulation of relevant model parameters underlying these phenomena.
Interventions
DRUG
Rivastigmine Transdermal System
Rivastigmine doses will be administered transdermally using 9.5 mg/24 hr transdermal patches. Participants will be randomized to two treatments with oral rivastigmine vs. placebo separated by a 15-hour washout period (\>5 half-lives to eliminate any residual effects). This will require three separate visits: a baseline visit, a visit for the first transdermal treatment and a visit for the second transdermal treatment. All visits include fMRI scans. The first transdermal patch will be administered 8-14 hours before the scan. After the washout period, the second transdermal patch will be administered 8-14 hours before the scan. No study team member except for the unblinded team member will know which capsule the participant receives first. Because we are interested in rivastigmine as a probe for a pre-identified computational/physiological abnormality, we will median-split groups post-hoc for the purposes of analysis.
DRUG
Scopolamine
The authors have chosen to use scopolamine to determine the effects of cholinergic antagonism, as treatment with scopolamine demonstrates a dose-related increase in propensity toward conditioned hallucinations and in doses much higher than those proposed here, can cause spontaneous hallucinations. At the proposed dose, scopolamine has an excellent safety profile and has been used routinely for nearly 20 years for treatment of nausea due to surgery or motion sickness in adults and children. Scopolamine is available in the US only as a 1mg / 72 hours transdermal patch, and peak plasma levels are reached within 24 hours. This standard dosage level is very well tolerated in the general population.
DRUG
Placebo Patch
Participants in Aim 2 will receive a placebo patch versus rivastigmine patch.
DRUG
Placebo Patch
Participants in Aim 1 will receive a placebo patch versus scopolamine patch.
Primary outcome measures
Number of conditioned hallucinations exhibited during saline vs placebo administration
Time frame: During fMRI scans / task completion which will take approximately 90 minutes
Participants will perform the Conditioned Hallucinations task while in the scanner; the authors hypothesize that number of conditioned hallucinations exhibited during the task will be higher under placebo than physostigmine, but only in those who have high prior weighting on baseline assessment.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- English speaking
- Right handedness
- Diagnosed with schizophrenia schizoaffective, schizophreniform, schizotypal, or brief psychotic disorder
- History of auditory verbal hallucinations occurring at least weekly
Exclusion criteria
- Current substance dependence or active use as determined by drug test.
- Any neurological, medical or developmental problem that is known to impair cognition significantly
- Contraindications for MR scanning including metallic implants of any kind, pacemakers and history of accidents with metal, claustrophobia
- History of seizures
- History of violence
- History of suicide
- Pregnancy (determined by urine pregnancy test)
- Concurrent participation in any other intervention study
- History of urinary retention
- History of delirium
- Current use of any cholinergic or anticholinergic medication
- History of asthma, diabetes, and cardiovascular disease
- Evidence of cardiovascular disease on EKG
- Individuals who have been on dopamine-2 antagonists for less than 6 months (to limit risk of EPS)
Where
- New Haven, Connecticut
Collaborators
National Institute of Mental Health (NIMH)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 5, 2025 · Source of record for eligibility and locations