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

NCT ID: NCT04004416

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 143 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-16
• Study Completion Date: 2025-02-28

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.

Detailed Description

• Please note the collaborator (NIMH) is requesting that an NCT number be obtained prior to receiving the award number.
• Initial assessment(s) may be done via videoconference due to Covid.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Healthy Controls

Group Type: PLACEBO_COMPARATOR

Placebo and fMRI

Intervention Type: 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.

Lorazepam and fMRI

Intervention Type: 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.

Early Psychosis patients

Group Type: EXPERIMENTAL

Placebo and fMRI

Intervention Type: 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.

Lorazepam and fMRI

Intervention Type: 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.

Schizophrenia or Schizoaffective disorder patients

Group Type: EXPERIMENTAL

Placebo and fMRI

Intervention Type: 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.

Lorazepam and fMRI

Intervention Type: 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.

Bipolar disorder patients

Group Type: EXPERIMENTAL

Placebo and fMRI

Intervention Type: 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.

Lorazepam and fMRI

Intervention Type: 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.

Interventions

Placebo and fMRI

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.

Intervention Type: OTHER

Lorazepam and fMRI

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.

Intervention Type: DRUG

Other Intervention Names

inactive medication; Ativan

Eligibility Criteria

Inclusion Criteria

• 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;
• 16-35 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.

Exclusion:

• 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;
• 16- 60 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
• Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 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.

Exclusion:

• 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

Healthy control subjects:

• Ability and willingness to give informed consent to participate
• Age 16 - 60
• No history of (h/o) past or current mental illness (except for simple phobias), but prior h/o substance abuse ok if in remission for greater than 5 years
• Not taking any medication, prescription or non-prescription, with psychotropic effects (birth control medications allowed)
• No first-degree family members with a history of a psychotic disorder (including bipolar disorder)
• 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
• Size compatible with scanner gantry, e. g. men over 6 feet tall that weigh more than 250 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.

Exclusion:

• 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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Stephan F. Taylor

Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephan Taylor, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

R01MH118634-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HUM00162597

Identifier Type: -

Identifier Source: org_study_id