Trial Outcomes & Findings for 5HT2CR Balance in Brain Connectivity in Cocaine Dependence (NCT NCT03921151)

Last Updated: 2021-11-22

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

90 participants

Primary outcome timeframe

Baseline to 1 week

Results posted on

2021-11-22

Participant Flow

Participant milestones

Participant milestones
Measure	Cocaine-dependent Participants who use and are dependent on cocaine 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.	Non-drug Using Healthy Controls Participants who are not drug users 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.
Overall Study STARTED	46	44
Overall Study COMPLETED	35	28
Overall Study NOT COMPLETED	11	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Cocaine-dependent Participants who use and are dependent on cocaine 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.	Non-drug Using Healthy Controls Participants who are not drug users 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.
Overall Study Withdrawal by Subject	11	16

Baseline Characteristics

5HT2CR Balance in Brain Connectivity in Cocaine Dependence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cocaine-dependent n=35 Participants Participants who use and are dependent on cocaine 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.	Non-drug Using Healthy Controls n=28 Participants Participants who are not drug users 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.	Total n=63 Participants Total of all reporting groups
Age, Continuous	44.6 years STANDARD_DEVIATION 8.62 • n=5 Participants	34.29 years STANDARD_DEVIATION 12.5 • n=7 Participants	40.02 years STANDARD_DEVIATION 11.64 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	14 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	35 Participants n=5 Participants	28 Participants n=7 Participants	63 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	34 Participants n=5 Participants	24 Participants n=7 Participants	58 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants	28 participants n=7 Participants	63 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 1 week

Population: Change scores could not be calculated for 17 cocaine-dependent participants and 14 non-drug using participants due to a missing or unusable fMRI scan.

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

Outcome measures

Outcome measures
Measure	Cocaine-dependent n=18 Participants Participants who use and are dependent on cocaine 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.	Non-drug Using Healthy Controls n=14 Participants Participants who are not drug users 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.
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.	0.6889 percent of whole brain BOLD signal Interval 0.2164 to 1.1614	-1.1091 percent of whole brain BOLD signal Interval -1.9063 to -0.3119

SECONDARY outcome

Timeframe: Baseline to 1 week

Population: Change scores could not be calculated for 12 cocaine-dependent participants and 9 non-drug using participants due to a missing or unusable fMRI scan.

Change in fMRI activation during Attentional bias task with placebo dose vs Mirtazapine dose measured using whole brain blood oxygenation level dependent (BOLD) signal

Outcome measures

Outcome measures
Measure	Cocaine-dependent n=23 Participants Participants who use and are dependent on cocaine 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.	Non-drug Using Healthy Controls n=19 Participants Participants who are not drug users 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.
Change in Interaction of the 5-HT2CR Cys23Ser SNP and a 5-HT2AR Antagonist on the Functional Circuitry Underlying Cue Reactivity	-0.135 percent of BOLD signal Interval -0.2998 to 0.0298	0.2225 percent of BOLD signal Interval -0.0926 to 0.5377

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 1 week

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Cocaine-dependent n=35 participants at risk Participants who use and are dependent on cocaine 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.	Non-drug Using Healthy Controls n=28 participants at risk Participants who are not drug users 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.
Gastrointestinal disorders Nausea and dizziness	0.00% 0/35 • Adverse events were monitored during the first study visit (practice MRI) through the last study visit (Dose 2 MRI) approximately 1 week. During the practice MRI visit, adverse events (AEs) were recorded using the 24 hour questionnaire. During the Dose 1 and Dose 2 MRI visits, AEs were recorded using the 24 questionnaire (pre dose), Drug Effects Questionnaire (pre dose, 1.25 hr post dose, 3.75 hr post dose, 4.5 hr post dose), and neurological exam (5 hr post dose completed by physician). All AEs were entered into a secure REDCap database.	3.6% 1/28 • Number of events 1 • Adverse events were monitored during the first study visit (practice MRI) through the last study visit (Dose 2 MRI) approximately 1 week. During the practice MRI visit, adverse events (AEs) were recorded using the 24 hour questionnaire. During the Dose 1 and Dose 2 MRI visits, AEs were recorded using the 24 questionnaire (pre dose), Drug Effects Questionnaire (pre dose, 1.25 hr post dose, 3.75 hr post dose, 4.5 hr post dose), and neurological exam (5 hr post dose completed by physician). All AEs were entered into a secure REDCap database.

Additional Information

Liangsuo Ma, PhD

Virginia Commonwealth University

Phone: (804) 828-2871

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place