Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Toward a Computationally-Informed, Personalized Treatment for Hallucinations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04366518
Recruitment Status : Recruiting
First Posted : April 29, 2020
Last Update Posted : March 4, 2022
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Yale University

Brief 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.

Condition or disease Intervention/treatment Phase
Hallucinations, Auditory Psychosis Drug: Rivastigmine Transdermal Product Drug: Scopolamine Drug: Placebo Early Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Rivastigmine vs Placebo
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Toward a Computationally-Informed, Personalized Treatment for Hallucinations
Actual Study Start Date : July 15, 2021
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Scopolamine

Arm Intervention/treatment
Experimental: Aim 2: Those with psychosis/hallucinations
Participants who have a psychosis spectrum diagnosis and frequent auditory hallucinations will be given Rivastigmine patch versus placebo patch
Drug: Rivastigmine Transdermal Product
Consistent with safety and efficacy demonstrated in prior studies, the authors propose two three-hour treatments with a transdermal rivastigmine patch vs. placebo separated by a 16-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 patch and a visit for the second patch. This will be a blinded study and no study team member except for the unblinded team member will know which patch 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: Placebo
Participants in Aim 2 will receive a placebo patch versus rivastigmine patch

Placebo Comparator: Aim 1: Healthy Controls
Healthy controls will be given scopolamine patches versus placebo patch.
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
Participants in Aim 1 will receive a placebo patch versus scopolamine patch.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Prior-Weighting Parameter of the Hierarchical Gaussian Filter [ Time Frame: During fMRI scans / task completion which will take approximately 90 minutes ]
    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.

  2. Functional correlation with model belief trajectories [ Time Frame: During fMRI scans / task completion which will take approximately 90 minutes ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-65
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04366518


Contacts
Layout table for location contacts
Contact: Albert Powers, MD, PhD 203-974-7329 albert.powers@yale.edu
Contact: Brittany Quagan brittany.quagan@yale.edu

Locations
Layout table for location information
United States, Connecticut
Connecticut Mental Health Center Recruiting
New Haven, Connecticut, United States, 06519
Contact: Albert Powers, M.D., Ph.D         
Sponsors and Collaborators
Yale University
National Institute of Mental Health (NIMH)
Layout table for additonal information
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT04366518    
Other Study ID Numbers: 2000024774
R21MH122940 ( U.S. NIH Grant/Contract )
First Posted: April 29, 2020    Key Record Dates
Last Update Posted: March 4, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Hallucinations
Perceptual Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Scopolamine
Rivastigmine
Butylscopolammonium Bromide
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents
Adjuvants, Anesthesia
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Mydriatics
Cholinergic Antagonists
Muscarinic Antagonists
Parasympatholytics