Lorazepam Effects on Neuroimaging Measures

Lorazepam Effects on Neuroimaging Measures: A Pilot Study

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.

Study Overview

• Status: Withdrawn
• Conditions: Neuroimaging; Lorazepam
• Intervention / Treatment: Drug: Lorazepam 1Mg Tablet; Drug: Placebo

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Glen Oaks, New York, United States, 11004
      • The Zucker Hillside Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged 18-40
4. In general good health as evidenced by medical history
5. Ability to take oral medication and be willing to adhere to the study medication regimen
6. 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:

1. Pregnancy or lactation
2. Contraindications to MR imaging (i.e. pacemaker)
3. Known allergic reactions to components of the lorazepam
4. Current smoker or tobacco use
5. Concurrent use of any psychotropic medications, anticonvulsants, opioids or any other medication with effects on the CNS.
6. Acute narrow-angle glaucoma
7. Current or past history of a substance use disorder and/or a positive urine toxicology test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lorazepam first; 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; 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.; Drug: Placebo; Placebo will be purchased and encapsulated by the pharmacy at the Zucker Hillside Hospital.
Placebo Comparator: Placebo first; 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; 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.; Drug: Placebo; Placebo will be purchased and encapsulated by the pharmacy at the Zucker Hillside Hospital.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Northwell Health
• Investigators: Principal Investigator: Juan A Gallego, MD, Northwell Health

Publications and helpful links

General Publications

• Sarpal DK, Argyelan M, Robinson DG, Szeszko PR, Karlsgodt KH, John M, Weissman N, Gallego JA, Kane JM, Lencz T, Malhotra AK. Baseline Striatal Functional Connectivity as a Predictor of Response to Antipsychotic Drug Treatment. Am J Psychiatry. 2016 Jan;173(1):69-77. doi: 10.1176/appi.ajp.2015.14121571. Epub 2015 Aug 28.
• Sarpal DK, Robinson DG, Lencz T, Argyelan M, Ikuta T, Karlsgodt K, Gallego JA, Kane JM, Szeszko PR, Malhotra AK. Antipsychotic treatment and functional connectivity of the striatum in first-episode schizophrenia. JAMA Psychiatry. 2015 Jan;72(1):5-13. doi: 10.1001/jamapsychiatry.2014.1734.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: December 11, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): May 27, 2022
• Last Update Submitted That Met QC Criteria: May 23, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: healthy volunteers; spectroscopy; functional connectivity; lorazepam
• Additional Relevant MeSH Terms: 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: 20-0773

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes