Lorazepam Effects on Neuroimaging Measures

Study Overview
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Brief Summary
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This within-subject, double blind, randomized controlled study will investigate the effects of a widely used benzodiazepine (BZD), lorazepam, on various neuroimaging measures. The investigators will be assessing the relationship of lorazepam to resting state functional connectivity and other neuroimaging measures. Specifically, the investigators will be using a pre-identified metric, the striatal connectivity index (SCI), (Sarpal et al. 2015, 2016), a prognostic biomarker of treatment response assessing the connectivity between regions of the striatum and the cortex. The investigators hypothesize that lorazepam administration will be associated with greater SCI values compared with placebo administration; consistent with previous work suggesting short-acting benzodiazepines increase functional connectivity across brain networks.

Official Title
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Lorazepam Effects on Neuroimaging Measures: A Pilot Study

Conditions
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Lorazepam, Neuroimaging

Intervention / Treatment
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* Drug: Lorazepam 1Mg Tablet
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet all of the following criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged 18-40 In general good health as evidenced by medical history Ability to take oral medication and be willing to adhere to the study medication regimen For women of reproductive potential, negative pregnancy test and agreement to use a medically accepted birth control method. Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: Pregnancy or lactation Contraindications to MR imaging (i.e. pacemaker) Known allergic reactions to components of the lorazepam Current smoker or tobacco use Concurrent use of any psychotropic medications, anticonvulsants, opioids or any other medication with effects on the CNS. Acute narrow-angle glaucoma Current or past history of a substance use disorder and/or a positive urine toxicology test.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lorazepam first<br>This arm comprises of participants who were randomized to receive lorazepam 1 mg prior to the first MRI scan and then placebo on the second MRI scan a week later. | Drug: Lorazepam 1Mg Tablet<br>* 1 mg, white, five-sided (shield shape) tablet with a raised A on one side and BPI and 64 impressed on scored reverse side. NDC 0187-0064-01 - Bottles of 100 tablets; NDC 0187-0064-50 - Bottles of 500 tablets; NDC 0187-0064-10 - Bottles of 1000 tablets. The pharmacy at the Zucker Hillside Hospital will encapsulate both lorazepam 1 mg and placebo pills to make them look the same. On the day of the scan, the research coordinator or the PI will pick up the blinded study medication (lorazepam or placebo) and will administer it to the participant. One hour later, the participant will be placed in the scanner to complete the MRI.<br>Drug: Placebo<br>* Placebo will be purchased and encapsulated by the pharmacy at the Zucker Hillside Hospital.<br>|
| Placebo Comparator: Placebo first<br>This arm comprises of participants who were randomized to receive placebo prior to the first MRI scan and then lorazepam 1 mg orally prior to the second MRI scan a week later. | Drug: Lorazepam 1Mg Tablet<br>* 1 mg, white, five-sided (shield shape) tablet with a raised A on one side and BPI and 64 impressed on scored reverse side. NDC 0187-0064-01 - Bottles of 100 tablets; NDC 0187-0064-50 - Bottles of 500 tablets; NDC 0187-0064-10 - Bottles of 1000 tablets. The pharmacy at the Zucker Hillside Hospital will encapsulate both lorazepam 1 mg and placebo pills to make them look the same. On the day of the scan, the research coordinator or the PI will pick up the blinded study medication (lorazepam or placebo) and will administer it to the participant. One hour later, the participant will be placed in the scanner to complete the MRI.<br>Drug: Placebo<br>* Placebo will be purchased and encapsulated by the pharmacy at the Zucker Hillside Hospital.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To understand the impact of lorazepam on functional connectivity measures collected using resting state functional magnetic imaging (rs-fMRI). | SCI, a parameter that captures the connectivity between the stratum and the cortex, is a primary candidate for a prognostic biomarker that may guide individual treatment. Exploratory functional connectivity analyses between other brain regions will be conducted as well. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The goal is to study the impact of lorazepam on glutamate, glutamine and GABA in the striatum. | Metabolite concentrations measured in parts per million (ppm) for Glutamate, glutamine and GABA; obtained with Magnetic Resonance Spectroscopy (MRS). | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lorazepam, functional connectivity, spectroscopy, healthy volunteers