- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04004416
Multi-modal Assessment of Gamma-aminobutyric Acid (GABA) Function in Psychosis (GABAmech)
Multi-modal Assessment of 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). 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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Clara Steeby, BS
- Phone Number: 734-615-3645
- Email: GABAStudy@med.umich.edu
Study Contact Backup
- Name: Laura M Stchur, MSW
- Phone Number: 734-936-1323
- Email: lmarine@med.umich.edu
Study Locations
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48109
- Recruiting
- University of Michigan
-
Contact:
- Laura Stchur, MSW
- Phone Number: 734-936-1323
- Email: lmarine@med.umich.edu
-
Principal Investigator:
- Stephan Taylor, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Early psychosis (EP) patients:
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
Inclusion Criteria:
- 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:
Inclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Healthy Controls
|
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.
Other Names:
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.
Other Names:
|
Experimental: Early Psychosis patients
|
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.
Other Names:
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.
Other Names:
|
Experimental: Schizophrenia or Schizoaffective disorder patients
|
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.
Other Names:
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.
Other Names:
|
Experimental: Bipolar disorder patients
|
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.
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Blood Oxygen level dependent (BOLD) in medial frontal cortex while viewing affective pictures
Time Frame: 2 hours after ingestion of lorazepam/placebo
|
BOLD signal change in medial frontal cortex after lorazepam challenge during fMRI
|
2 hours after ingestion of lorazepam/placebo
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Stephan Taylor, MD, University of Michigan
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Schizophrenia Spectrum and Other Psychotic Disorders
- Bipolar and Related Disorders
- Schizophrenia
- Psychotic Disorders
- Mental Disorders
- Bipolar Disorder
- Mood Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiemetics
- Gastrointestinal Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Hypnotics and Sedatives
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Anticonvulsants
- Lorazepam
Other Study ID Numbers
- HUM00162597
- R01MH118634-01 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
The PI will share information about this/these trial(s) via timely registration, updates, and results reporting in ClinicalTrials.gov in accordance with NIH policy.
The PI will also upload data gathered in this proposal to an National Institute of Mental Health (NIMH)-designated central data, NIMH Data Archive (NDA), as prescribed by NOT-MH-15-012, working with NIMH program to determine the timing and extent of data sharing. This includes formulation of an enrollment strategy that will obtain the information necessary to generate a Global Unique Identifier (GUID) for each participant.
The consent form will include language indicating the intention to upload de-identified data into the central archive, and permission will be obtained from University of Michigan Institutional Review Board to do so. The budget includes a data manager to cover the costs of managing the data, building the data dictionary and harmonizing it with data structures.
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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