5HT2CR Balance in Brain Connectivity in Cocaine Dependence

NCT ID: NCT03921151

Last Updated: 2021-11-22

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-13

Study Completion Date

2019-01-24

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The overall goal of this project is to evaluate the role of molecular interactions between 5-HT2AR and 5-HT2CR in behavioral phenotypes that confer risk for cocaine dependence and relapse. Specifically, 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. Brain and behavioral responses to the 5-HT2AR blocking medication mirtazapine will be compared between subjects who have high and low functioning of the 5-HT2CR based on presence of a specific, functionally-relevant single nucleotide polymorphism (SNP) of the 5-HT2CR (Cys23Ser). The 5-HT2CR Cys23Ser SNP is thought to decrease the function of the protein and a preliminary observation indicates cocaine-dependent subjects carrying the CC genotype (Ser23 protein variant) display significantly higher cue reactivity. For Aims 1 and 2, two fMRI analysis methods will be used: 1) a voxelwise whole brain analysis; 2) a region of interest analysis based on proposed integrative circuitry shown in the model below. Because neuroimaging studies have shown that performance of impulsive action tasks and exposure to cocaine-associated cues (cue reactivity paradigms) activate brain regions in brain circuits in humans, impulsive action and cue reactivity may be engendered in related pathways. To explore this hypothesis, researchers will employ functional magnetic resonance imaging (fMRI)-based dynamic causal modeling (DCM) to ascertain the causal influences of one brain region over another. Employing DCM, researchers will uncover the effective connectivity within nodes of the neurocircuitry involved in impulsive action and cue reactivity. This project will parallel preclinical work studying the relationship between 5-HT2AR and 5-HT2CR on impulsive action and cue reactivity.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cocaine Dependence

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Cocaine-dependent

Participants who use and are dependent on cocaine

Group Type OTHER

Mirtazapine 15 MG Oral Tablet

Intervention Type 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.

Non-drug using Healthy Controls

Participants who are not drug users

Group Type OTHER

Mirtazapine 15 MG Oral Tablet

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Mirtazapine 15 MG Oral Tablet

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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Remeron

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Cocaine Dependent Subjects

1. Be English-speaking volunteers
2. Be aged between 18 and 60 years
3. Meet DSM-5 criteria for cocaine dependence
4. Have a self-reported history of using cocaine
5. Have hematology and chemistry laboratory tests that are within reference limits ( 10%) with the following exceptions: hemoglobin and hematocrit within normal limits (for fMRI).
6. Have a baseline EKG that demonstrates clinically normal sinus rhythm, clinically normal conduction, and no clinically significant abnormalities
7. 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.
8. 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

1. Be English-speaking volunteers
2. Be aged between 18 and 60 years
3. 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.
4. Have hematology and chemistry laboratory tests that are within reference limits ( 10%), with the following exceptions: hemoglobin and hematocrit within normal limits (for fMRI)
5. Have a baseline EKG that demonstrates clinically normal sinus rhythm, clinically normal conduction, and no clinically significant abnormalities
6. Have a medical history and brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician and the Principal investigator.
7. Have no metal fragments or other bodily metal (pacemaker) or significant claustrophobia that would put the subjects at risk for MRI scanning

Exclusion Criteria

Cocaine Dependent Subjects

1. Have any history or evidence suggestive of seizure disorder or brain injury.
2. Have any previous medically adverse reaction to mirtazapine or other antidepressants.
3. 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.
4. Have evidence of uncontrolled clinically significant heart disease or hypertension, as determined by the PI.
5. Have evidence of non-psychiatric medical illness including neuroendocrine, autoimmune, renal, hepatic, or active infectious disease.
6. Use of any medications or drugs that can affect the central nervous system other than cocaine, marijuana, alcohol caffeine and nicotine.
7. Have a positive HIV test.
8. 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.
9. 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

1. Meet DSM-5 criteria for any current or past Axis I disorder.
2. Meet DSM-5 criteria for an Axis II diagnosis of Borderline or Antisocial Personality Disorder.
3. Have any history or evidence suggestive of seizure disorder or brain injury.
4. Have any previous medically adverse reaction to mirtazapine or other antidepressants.
5. Have evidence of uncontrolled clinically significant heart disease or hypertension, as determined by the PI.
6. Have evidence of medical illness including neuroendocrine, autoimmune, renal, hepatic, or active infectious disease.
7. Use of any medications or drugs that can affect the central nervous system other than caffeine or nicotine.
8. Have a positive HIV test.
9. 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.
10. 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

The University of Texas Medical Branch, Galveston

OTHER

Sponsor Role collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

Virginia Commonwealth University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Frederick Moeller, M.D.

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

P20DA024157-04S1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HM15289

Identifier Type: -

Identifier Source: org_study_id