RecruitingEarly Phase 1NCT04366518

Toward a Computationally-Informed, Personalized Treatment for Hallucinations

Sponsor

Yale University

Enrollment

35 participants

Start Date

Jul 15, 2021

Study Type

INTERVENTIONAL

Conditions

Psychosis Hallucinations, Auditory

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 65 Years

Plain Language Summary

Simplified for easier understanding

This study is developing a personalized brain stimulation treatment (using a technique called TMS — transcranial magnetic stimulation) for people who hear voices as part of a psychotic disorder. By using MRI brain scans to precisely target the treatment, researchers hope to reduce the frequency and distress of auditory hallucinations. **You may be eligible if:** - You are 18 to 65 years old - You are right-handed - You speak English - You have a diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, schizotypal disorder, or brief psychotic disorder - You experience hearing voices (auditory verbal hallucinations) at least once a week **You may NOT be eligible if:** - You are currently dependent on substances or have active drug use detected on testing - You have a neurological condition or developmental disorder that significantly affects cognition - You have any metal implants, pacemakers, or claustrophobia (which prevent MRI) - You have a history of seizures, violence, or suicide attempts - You are pregnant Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGRivastigmine 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.

DRUGScopolamine

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.

DRUGPlacebo Patch

Participants in Aim 2 will receive a placebo patch versus rivastigmine patch.

DRUGPlacebo Patch

Participants in Aim 1 will receive a placebo patch versus scopolamine patch.