Lorazepam Effects on Neuroimaging Measures

NCT04671836 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: 20-0773
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lorazepam; Neuroimaging

Keywords

lorazepam; functional connectivity; spectroscopy; healthy volunteers

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• The goal is to study the impact of lorazepam on glutamate, glutamine and GABA in the striatum.

  2 weeks

Study Arms (2)

Lorazepam first

EXPERIMENTAL

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; Drug: Placebo

Placebo first

PLACEBO COMPARATOR

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; Drug: Placebo

Interventions

Lorazepam 1Mg Tablet DRUG

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.

Lorazepam first; Placebo first

Placebo DRUG

Placebo will be purchased and encapsulated by the pharmacy at the Zucker Hillside Hospital.

Lorazepam first; Placebo first

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

The Zucker Hillside Hospital

Glen Oaks, New York, 11004, United States

Location

Related Publications (2)

• 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.

  PMID: 26315980 RESULT

• 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.

  PMID: 25372846 RESULT

MeSH Terms

Interventions

Lorazepam; Tablets

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Juan A Gallego, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Investigator

Study Record Dates

• First Submitted: December 11, 2020
• First Posted: December 17, 2020
• Study Start: January 1, 2022
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: May 27, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)