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Completed

NCT Number: NCT04004416

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

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 like bipolar disorder). The study will also enroll eligible participants between the ages of 18 and 60 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 be two separate functional magnetic resonance imaging (fMRI) sessions in which lorazepam or placebo will be given prior to the fMRI. During the fMRI, the participants will also be asked to answer questions. Additionally, the participants will have their blood drawn, vital signs will be taken, they will be asked to complete more qols, and women of childbearing potential will have a urine pregnancy test.

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Key information

Age range

16 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University of Michigan

Ann Arbor, Michigan, 48109, United States

About this study

  • 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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Early psychosis (EP) patients:

Inclusion criteria

  • Ability and willingness to give informed consent to participate;
  • 16-35 years old
  • 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).
  • 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 the EP sample, 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 fMRI session
  • Ability to tolerate small, enclosed spaces without anxiety
  • Vision equal to or better than 20/40 on a Snellen chart, with correction if necessary
  • 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 difficulty fitting into the fMRI scanner properly.

Exclusion criteria

  • If a woman of childbearing 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
  • Hypersensitivity to benzodiazepines or to components of the formulation, per judgment of the principal investigator (PI)
  • Disorders affected by benzodiazepines, such as compromised respiratory function, e.g., chronic obstructive pulmonary disease, or acute, narrow angle glaucoma, per judgment of the principal investigator (PI)

Schizophrenia/schizoaffective (SCZ) and bipolar affective disorder (BAD) patients:

Inclusion criteria

  • Ability and willingness to give informed consent to participate;
  • 16- 60 years old
  • Meets DSM5 criteria for schizophrenia, schizoaffective disorder, other specified/unspecified psychotic 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 Columbia-Suicide Severity Rating Scale (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 fMRI session
  • Ability to tolerate small, enclosed spaces without anxiety
  • Vision equal to or better than 20/40 on a Snellen chart, with correction if necessary
  • 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 difficulty fitting into the fMRI scanner properly.

Exclusion criteria

  • If a woman of childbearing 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
  • Hypersensitivity to benzodiazepines or to components of the formulation, per judgment of the principal investigator (PI)
  • Disorders affected by benzodiazepines, such as compromised respiratory function, e.g., chronic obstructive pulmonary disease, or acute, narrow angle glaucoma, per judgment of the principal investigator (PI)

Healthy control subjects:

Inclusion criteria

  • Ability and willingness to give informed consent to participate
  • 18- 60 years old
  • No history of (h/o) past or current mental illness (except for simple phobias), but prior h/o substance abuse okay 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
  • Vision equal to or better than 20/40 on a Snellen chart, with correction if necessary
  • 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 difficulty fitting into the fMRI scanner properly.

Exclusion criteria

  • If a woman of childbearing 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
  • Hypersensitivity to benzodiazepines or to components of the formulation, per judgment of the principal investigator (PI)
  • Disorders affected by benzodiazepines, such as compromised respiratory function, e.g., chronic obstructive pulmonary disease, or acute, narrow angle glaucoma, per judgment of the principal investigator (PI)

Treatment and study plan

Placebo and fMRI

Other

There will be two fMRIs done after the initial assessment and approximately 28 days apart. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. A dose of Placebo will be given approximately 80-90 minutes prior to entering the fMRI scanner. Participants will complete assessments (vitals, questionnaires) and an optional blood draw prior to having each fMRI. Participants will be asked to rate pleasant/unpleasant pictures during their initial assessment visit and to view them during the fMRI.

Other names: inactive medication

Lorazepam and fMRI

Drug

There will be two fMRIs done after the initial assessment and approximately 28 days apart. Females may need to have this scheduled to coincide with a certain phase of their menstrual cycle. 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 approximately 80-90 minutes prior to entering the fMRI scanner. Participants will complete assessments (vitals, questionnaires) and optional blood draw prior to having each fMRI. Participants will be asked to rate pleasant/unpleasant pictures during their initial assessment visit and to view them during the fMRI.

Other names: Ativan

Primary outcomes

  1. Blood Oxygen Level Dependent (BOLD) Change in Medial Frontal Cortex While Viewing Affective Pictures

    Time frame: Approximately 28 days

    Change in brain activity in the medial frontal cortex after being given lorazepam, a medication that changes the activity of GABAergic neurons. Results reflect the difference/change in brain signal between the lorazepam scan and the placebo scan. BOLD change in the dorsomedial prefrontal cortex (dmPFC) was summarized using MATLAB (MatrixLaboratory)'s SPM (Statistical Parametric Mapping) package for eigenvariate extraction, which extracts the first principal component of the voxel time series within an region of interest (ROI). The resulting values are in arbitrary units (AU) reflecting variance-normalized signal after temporal filtering and serial correlation correction, which removes absolute signal scaling. While AU values are not directly interpretable as percent signal change, they preserve relative differences in BOLD change across conditions and are appropriate for statistical comparison.

Other outcomes

  1. Levels of Negative Affect

    Time frame: Approximately 28 days

    Levels of negative affect were calculated from a PCA of self-report scales: Psychological Stress Index (PSI9; 9-item, Min=0, Max=36, higher=more stress), negative emotions from Modified Differential Emotions Scale (mDES; 8-item subscale, Min=0, Max=32, higher=more negative emotion), Beck Depression Inventory (BDI; 21-item, Min=0, Max=63, higher=more depression). Each measure was completed twice (pre-placebo and pre-drug). The PCA used the prcomp function in R (version 4.5.3), with variables from each scale centered and scaled to unit variance. The 1st principal component of PCA was used as index of general negative affect. This component explained 79% of the total variance across the 6 input measures. Individual component scores were extracted for each participant (Range Min=-3.352, Max=7.067, arbitrary units, higher values=more negative affect/worse outcome).

Sponsors and collaborators

Lead sponsor

University of Michigan

Other

Collaborators

  • National Institute of Mental Health (NIMH)

Registry information

Official study title

Multi-modal Assessment of GABA Function in Psychosis

Acronym: GABAmech

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
Jul 2, 2019
Registry last updated
Jun 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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