5HT2CR Balance in Brain Connectivity in Cocaine Dependence

NCT03921151 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HM15289P20DA024157-04S1
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This project will evaluate the role of the 5-HT2CR:5-HT2AR balance in impulsive action and cue reactivity in cocaine-dependent subjects as compared to non-drug using controls.

Conditions

Cocaine Dependence

Outcome Measures

Primary Outcomes (1)

• Change in Interaction of the Serotonin Receptor (5-HTR) Type-2C Cys23Ser Single Nucleotide Polymorphism (SNP) and a 5-HT2AR Antagonist on the Functional Circuitry Underlying Impulsive Action.

  Change in fMRI activation during Go/NoGo (impulsivity) task with placebo dose vs Mirtazapine dose. Brain activation measured using blood-oxygen-level dependent (BOLD) contrast

  Baseline to 1 week

Secondary Outcomes (1)

• Change in Interaction of the 5-HT2CR Cys23Ser SNP and a 5-HT2AR Antagonist on the Functional Circuitry Underlying Cue Reactivity

  Baseline to 1 week

Other Outcomes (4)

• Change in Effective Connectivity Involved in the 5-HT2AR:5-HT2CR Homeostasis Impulsive Action

  Baseline to 1 week

• Change in Effective Connectivity Involved in the 5-HT2AR:5-HT2CR Homeostasis Cue Reactivity

  Baseline to 1 week

• Change in Explore Interactions Between Other 5-HT2CR SNPs and Brain Activation During Attentional Bias Task After a 5- HT2AR Antagonist

  Baseline to 1 week

Study Arms (2)

Cocaine-dependent

OTHER

Participants who use and are dependent on cocaine

Drug: Mirtazapine 15 MG Oral Tablet

Non-drug using Healthy Controls

OTHER

Participants who are not drug users

Drug: Mirtazapine 15 MG Oral Tablet

Interventions

Mirtazapine 15 MG Oral Tablet DRUG

The intervention will be a 15mg of mirtazapine oral tablet given to participants prior to their treatment scan and assessments. In order to ensure that biases or social desirability do not contaminate baseline assessments, all participants will also be given a tablet consisting of dextrose in gelatin prior to their baseline scan and assessment.

Also known as: Remeron

Cocaine-dependent; Non-drug using Healthy Controls

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Cocaine Dependent Subjects
• Be English-speaking volunteers
• Be aged between 18 and 60 years
• Meet DSM-5 criteria for cocaine dependence
• Have a self-reported history of using cocaine
• Have hematology and chemistry laboratory tests that are within reference limits ( 10%) with the following exceptions: hemoglobin and hematocrit within normal limits (for fMRI).
• Have a baseline EKG that demonstrates clinically normal sinus rhythm, clinically normal conduction, and no clinically significant abnormalities
• Have a medical history and physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician and the principal investigator.
• Have no metal fragments or other bodily metal (e.g., pacemaker) or significant claustrophobia that would put the subjects at risk for MRI scanning.
• Non-Drug Using Controls
• Be English-speaking volunteers
• Be aged between 18 and 60 years
• Have no past history of Psychiatric or non-Psychiatric medical disorders which could affect the central nervous system as assessed by SCID and physical examination.
• Have hematology and chemistry laboratory tests that are within reference limits ( 10%), with the following exceptions: hemoglobin and hematocrit within normal limits (for fMRI)
• Have a baseline EKG that demonstrates clinically normal sinus rhythm, clinically normal conduction, and no clinically significant abnormalities

You may not qualify if:

• Cocaine Dependent Subjects
• Have any history or evidence suggestive of seizure disorder or brain injury.
• Have any previous medically adverse reaction to mirtazapine or other antidepressants.
• Have neurological or psychiatric disorders, such as (a) psychosis, bipolar illness or major depression as assessed by SCID; (b) organic brain disease or dementia assessed by clinical interview; (c) history of any psychiatric disorder that would require ongoing treatment or that would make study compliance difficult; and (d) history of suicide attempts within the past 3 months and/or current suicidal ideation/plan.
• Have evidence of uncontrolled clinically significant heart disease or hypertension, as determined by the PI.
• Have evidence of non-psychiatric medical illness including neuroendocrine, autoimmune, renal, hepatic, or active infectious disease.
• Use of any medications or drugs that can affect the central nervous system other than cocaine, marijuana, alcohol caffeine and nicotine.
• Have a positive HIV test.
• Be pregnant or nursing. Other females must either be unable to conceive (i.e., surgically sterilized, sterile, or postmenopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device, condoms, or spermicide). All females must provide negative pregnancy urine tests before study entry, weekly during the study, and at the end of study participation.
• Have any other illness, condition, or use of psychotropic medications, which in the opinion of the PI and/or the admitting physician would preclude safe and/or successful completion of the study.
• Non-Drug Using Controls
• Meet DSM-5 criteria for any current or past Axis I disorder.
• Meet DSM-5 criteria for an Axis II diagnosis of Borderline or Antisocial Personality Disorder.
• Have any history or evidence suggestive of seizure disorder or brain injury.
• Have any previous medically adverse reaction to mirtazapine or other antidepressants.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• The University of Texas Medical Branch, Galveston: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Mirtazapine; Tablets

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Liangsuo Ma, PhD
• Organization: Virginia Commonwealth University

liangsuo.ma@vcuhealth.org

(804) 828-2871

Study Officials

• Frederick Moeller, M.D.

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: April 19, 2019
• Study Start: May 13, 2014
• Primary Completion: January 24, 2019
• Study Completion: January 24, 2019
• Last Updated: November 22, 2021
• Results First Posted: November 22, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)