Health TrialsbyHealthPanel

Toward a Computationally-Informed, Personalized Treatment for Hallucinations

ConditionsHallucinations, AuditoryPsychosis
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-65
SponsorYale University

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

Age 18-65

English speaking

Right handedness

Diagnosed with schizophrenia schizoaffective, schizophreniform, schizotypal, or brief psychotic disorder

Disqualifiers

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

Trial design

Design model

Crossover

Treatments tested in this trial

  • Rivastigmine Transdermal System

    Drug

    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.

  • Scopolamine

    Drug

    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.

  • Placebo Patch

    Drug

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

  • Placebo Patch

    Drug

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

Treatment groups

35 Participants
are divided into 2 treatment groups
Group A: Aim 2: Those with psychosis/hallucinationsExperimental treatment 2 interventions
Group B: Aim 1: Healthy ControlsPlacebo comparator 2 interventions

Trial outcomes

Primary outcomes

1

Number of conditioned hallucinations exhibited during saline vs placebo administration

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.

Time frame
During fMRI scans / task completion which will take approximately 90 minutes

Secondary outcomes

1

Prior-Weighting Parameter of the Hierarchical Gaussian Filter

Behavioral responses will be used to fit a parameter of the Hierarchical Gaussian Filter model corresponding to the ratio of precision of priors to precision of incoming sensory evidence.

Time frame
During fMRI scans / task completion which will take approximately 90 minutes
2

Functional correlation with model belief trajectories

Behavioral responses will be used to fit belief trajectories across the course of the experiment, and whole-brain analyses will measure correlation of brain activity with these computed trajectories.

Time frame
During fMRI scans / task completion which will take approximately 90 minutes

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Yale University

Lead sponsor

National Institute of Mental Health (NIMH)

Collaborator

Source ClinicalTrials.gov
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