Multi-modal Assessment of Gamma-aminobutyric Acid (GABA) Function in Psychosis

NCT04004416 | Completed Phase 4 FDA Drug

• 2 other identifiers: HUM00162597R01MH118634-01
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to better understand mental illness and will test the hypotheses that while viewing affective stimuli, patient groups will show increased blood oxygenation level dependent (BOLD) signal by fMRI after lorazepam. This study will enroll participants between the ages of 16 and 60, who have a psychotic illness (such as psychosis which includes conditions like schizophrenia, schizoaffective disorder, and mood disorders). The study will also enroll eligible participants without any psychiatric illness, to compare their brains. The study will require participants to have 3-4 sessions over a few weeks. The initial assessments (may be over two visits) will include a diagnostic interview and several questionnaires (qols) to assess eligibility. Subsequently, there will will be two separate functional magnetic resonance imaging (fMRI) sessions in which lorazepam or placebo will be given prior to the MRI. During the fMRI the participants will also be asked to answer questions. Additionally, the participants will have their blood drawn, women of child bearing potential will have a urine pregnancy test, vital signs taken, and asked to complete more qols.

Conditions

Schizophrenia; Bipolar Disorder; Healthy; Psychosis; Schizophreniform Disorders; Schizo Affective Disorder; Major Depression With Psychotic Features

Outcome Measures

Primary Outcomes (1)

• Blood Oxygen level dependent (BOLD) in medial frontal cortex while viewing affective pictures

  BOLD signal change in medial frontal cortex after lorazepam challenge during fMRI

  2 hours after ingestion of lorazepam/placebo

Study Arms (4)

Healthy Controls

PLACEBO COMPARATOR

Other: Placebo and fMRI; Drug: Lorazepam and fMRI

Early Psychosis patients

EXPERIMENTAL

Other: Placebo and fMRI; Drug: Lorazepam and fMRI

Schizophrenia or Schizoaffective disorder patients

EXPERIMENTAL

Other: Placebo and fMRI; Drug: Lorazepam and fMRI

Bipolar disorder patients

EXPERIMENTAL

Other: Placebo and fMRI; Drug: Lorazepam and fMRI

Interventions

Placebo and fMRI OTHER

A dose of Placebo will be given 90 minutes prior to entering the fMRI scanner. At each visit volunteers will complete assessments (vitals, qols) and optional blood draw prior to having an fMRI. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. During the fMRI participants will be asked to view pleasant/unpleasant pictures and rate them while you are inside the scanner.

Also known as: inactive medication

Bipolar disorder patients; Early Psychosis patients; Healthy Controls; Schizophrenia or Schizoaffective disorder patients

Lorazepam and fMRI DRUG

A dose of Lorazepam (assigned to one of two dose levels between subjects: 0.01 mg/kg or 0.02 mg/kg) will be given 90 minutes prior to entering the fMRI scanner. At each visit volunteers will complete assessments (vitals, qols) and optional blood draw prior to having an fMRI. There will be two fMRIs done approximately 1 week apart and after the assessment visit. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. During the fMRI participants will be asked to view pleasant/unpleasant pictures and rate them while you are inside the scanner.

Also known as: Ativan

Bipolar disorder patients; Early Psychosis patients; Healthy Controls; Schizophrenia or Schizoaffective disorder patients

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Meets DSM5 criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, bipolar disorder type 1, with history of psychosis, major depressive disorder, with history of psychosis, brief psychotic disorder, or other specified/unspecified psychotic disorder; or, meets SIPS criteria for Presence of Psychotic Symptoms or Brief Intermittent Psychotic Syndrome (BIPS).
• Ability and willingness to give informed consent to participate;
• years old
• Positive symptom onset ≤ 2 years
• No history of active substance use disorder in the past 2 months
• Not currently on an involuntary treatment order
• Not taking chronic narcotics, barbiturates, benzodiazepines
• Absence of suicidal thoughts with plans or intentions, as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
• No increases in psychotropic medication within the prior 4 weeks reflecting clinical instability and for half of EP sample, or not taking antipsychotic medication within the prior 4 weeks. Patients may take as needed doses of benzodiazepines as clinically prescribed, as long as those doses are not required within 5 half-lives of an MRI session
• Ability to tolerate small, enclosed spaces without anxiety
• No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (metal workers excluded), neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, cerebral spinal fluid (CSF)shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, automatic implantable defibrillators
• Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 pounds (lbs), men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficult fitting into the fMRI scanner properly.

You may not qualify if:

• If a woman of child bearing age, not pregnant or trying to become pregnant
• History of serious neurological illness or current medical condition that could compromise brain function, such as liver failure
• History of closed head injury, for example (e.g.) loss of consciousness \> \~5 min, hospitalization, neurological sequela
• Schizophrenia/schizoaffective (SCZ) and bipolar affective disorder (BAD) patients
• Ability and willingness to give informed consent to participate;
• years old
• Meets DSM- 5 criteria for schizophrenia, or schizoaffective disorder, or bipolar disorder type 1, with history of psychosis bipolar affective disorder
• Duration of positive symptom onset \> 2 years
• No history of active substance use disorder in the past 2 months
• Not currently on an involuntary treatment order
• Not taking chronic narcotics, barbiturates, benzodiazepines
• Absence of suicidal thoughts with plans or intentions, as assessed by C-SSRS
• No increases in psychotropic medication within the prior 4 weeks reflecting clinical instability. Patients may take as needed doses of benzodiazepines as clinically prescribed, as long as those doses are not required within 5 half-lives of an MRI session
• Ability to tolerate small, enclosed spaces without anxiety
• No metals, implants or metallic substances within or on the body that might cause adverse effects to the subject in a strong magnetic field, or interfere with image acquisition, e. g. aneurysm clips, retained particles (metal workers excluded), neurostimulators, foil-backed transdermal patches, carotid or cerebral stents, CSF shunts; magnetic dental implants, ferromagnetic ocular implants, pacemakers, automatic implantable defibrillators

Sponsors & Collaborators

• University of Michigan: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Schizophrenia; Bipolar Disorder; Psychotic Disorders

Interventions

Lorazepam

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Bipolar and Related Disorders; Mood Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Stephan Taylor, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Study coordinator and participant are blinded to medication administration.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Model Details: The two MRI sessions will will be scheduled about 1 week apart. If you are a woman, we may need to schedule the scanning session to coincide with a certain phase of your menstrual cycle.

Study Record Dates

• First Submitted: June 28, 2019
• First Posted: July 2, 2019
• Study Start: January 16, 2020
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: March 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: De-identified data will be entered into the NDA within 1 year of the conclusion of the study.
• Access Criteria: No additional access restrictions will be placed on the de-identified data beyond those that are standard for the NDA.

Locations

US (1)