n-Acetylcysteine and Cocaine

Motivation for Cocaine and Non-Drug Reinforcers: Targeting Glutamate Homeostasis

Status

Completed

Phases

Early Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02141620

Enrollment

Registered

2014-05-19

Start date

2014-05-31

Completion date

2016-04-30

Last updated

2017-01-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cocaine Abuse, Cocaine Dependence

Brief summary

This study will determine the initial efficacy, safety and tolerability of n-acetylcysteine as a pharmacotherapy for cocaine dependence. A rigorous, inpatient human laboratory study will be conducted in which the subjective, physiological and reinforcing effects of cocaine are evaluated during maintenance on placebo and n-acetylcysteine.

Interventions

DRUGCocaine

The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and n-acetylcysteine.

DRUGn-Acetylcysteine

DRUGPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

TRIPLE (Subject, Caregiver, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

* Current cocaine use * Current cigarette smoker

Exclusion criteria

* Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant * Current or past histories of substance abuse or dependence that are deemed by the study physicians to interfere with study completion * History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation * Females not currently using effective birth control * Contraindications to cocaine or n-acetylcysteine * History of schizophrenia in first degree relative

Design outcomes

Primary

Measure	Time frame	Description
Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	One test per cocaine dose level per intervention for each participant over his/her approximate 2 week inpatient admission.	The reinforcing effects of cocaine were determined using a modified progressive ratio procedure (Stoops et al., 2010) in which subjects made 6 choices between available each available cocaine dose and money (US$0.25). Reinforcing effects are measured for each cocaine dose during both buspirone and placebo maintenance.

Secondary

Measure	Time frame	Description
Peak Score on Sedative Subscale of the Adjective Rating Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects completed 16 items that loaded into the Sedative Subscale of the Adjective Rating Scale. The items were rated 0-4 on a Likert-type scale and the sum for the 16 sedative items was summed to yield the Sedative Subscale score. The maximum score for this scale was 64, the minimum was 0. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Score on Stimulant Subscale of the Adjective Rating Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects completed 16 items that loaded into the Stimulant Subscale of the Adjective Rating Scale. The items were rated 0-4 on a Likert-type scale and the sum for the 16 sedative items was summed to yield the Stimulant Subscale score. The maximum score for this scale was 64, the minimum was 0. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Active, Alert, Energetic on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Active, Alert, Energetic on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Any Effect on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Any Effect on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Bad Effects on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Bad Effects on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Good Effects on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Good Effects on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of High on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of High on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Irregular/Racing Heartbeat on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Irregular/Racing Heartbeat on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Like Drug on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Like Drug on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Nauseous on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Nauseous on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Nervous/Anxious on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Nervous/Anxious on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Willing to Pay For on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Willing to Pay For on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Euphoric on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Euphoric on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Performance Improved on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Performance Improved on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Restless on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Restless on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Rush on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Rush on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Shaky/Jittery on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Shaky/Jittery on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Sluggish/Fatigued/Lazy on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Sluggish/Fatigued/Lazy on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Stimulated on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Stimulated on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Willing to Take Again on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Willing to Take Again on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Talkative/Friendly on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Talkative/Friendly on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Diastolic Blood Pressure	This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Diastolic blood pressure was measured with an automated monitor. Higher values represent greater diastolic pressure. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Systolic Blood Pressure	This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Systolic blood pressure was measured with an automated monitor. Higher values represent greater systolic pressure. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Heart Rate	This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Heart rate was measured with an automated monitor. Higher values represent greater heart rate. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Temperature	This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Oral temperature was measured with an automated monitor. Higher values represent greater temperature. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.
Peak Ratings of Performance Impaired on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.	Subjects rated their feelings of Performance Impaired on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.

Countries

United States

Participant flow

Participants by arm

Arm	Count
All Study Participants All subjects who completed the study.	14
Total	14

Withdrawals & dropouts

Period	Reason	FG000	FG001
Treatment Condition 1 (7 Days)	Adverse Event	1	0

Baseline characteristics

Characteristic	All Study Participants
Age, Continuous	42.6 years STANDARD_DEVIATION 5.4
Gender Female	3 Participants
Gender Male	11 Participants
Region of Enrollment United States	14 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1 / 8	0 / 7
serious Total, serious adverse events	0 / 8	0 / 7

Outcome results

Primary

Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative

The reinforcing effects of cocaine were determined using a modified progressive ratio procedure (Stoops et al., 2010) in which subjects made 6 choices between available each available cocaine dose and money (US$0.25). Reinforcing effects are measured for each cocaine dose during both buspirone and placebo maintenance.

Time frame: One test per cocaine dose level per intervention for each participant over his/her approximate 2 week inpatient admission.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	Placebo Cocaine	1.0 Number of Cocaine Choices	Standard Deviation 2.2
Placebo	Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	30 mg Cocaine	3.4 Number of Cocaine Choices	Standard Deviation 2.6
Placebo	Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	60 mg Cocaine	3.5 Number of Cocaine Choices	Standard Deviation 2.8
n-Acetylcysteine	Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	Placebo Cocaine	0.1 Number of Cocaine Choices	Standard Deviation 0.5
n-Acetylcysteine	Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	30 mg Cocaine	3.9 Number of Cocaine Choices	Standard Deviation 2.4
n-Acetylcysteine	Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	60 mg Cocaine	3.9 Number of Cocaine Choices	Standard Deviation 2.4

Secondary

Peak Diastolic Blood Pressure

Diastolic blood pressure was measured with an automated monitor. Higher values represent greater diastolic pressure. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.

Time frame: This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Peak Diastolic Blood Pressure	Placebo Cocaine	75.9 mm Hg	Standard Error 2.2
Placebo	Peak Diastolic Blood Pressure	30 mg Cocaine	81.1 mm Hg	Standard Error 1.8
Placebo	Peak Diastolic Blood Pressure	60 mg Cocaine	82.4 mm Hg	Standard Error 3
n-Acetylcysteine	Peak Diastolic Blood Pressure	60 mg Cocaine	79.9 mm Hg	Standard Error 2.4
n-Acetylcysteine	Peak Diastolic Blood Pressure	Placebo Cocaine	74.9 mm Hg	Standard Error 2.3
n-Acetylcysteine	Peak Diastolic Blood Pressure	30 mg Cocaine	82.3 mm Hg	Standard Error 2.4

Secondary

Peak Heart Rate

Heart rate was measured with an automated monitor. Higher values represent greater heart rate. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.

Time frame: This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine and placebo maintenance conditions.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Peak Heart Rate	Placebo Cocaine	72.4 beats per minute	Standard Error 1.8
Placebo	Peak Heart Rate	30 mg Cocaine	82.2 beats per minute	Standard Error 4.4
Placebo	Peak Heart Rate	60 mg Cocaine	84.3 beats per minute	Standard Error 4.3
n-Acetylcysteine	Peak Heart Rate	Placebo Cocaine	73.6 beats per minute	Standard Error 2.5
n-Acetylcysteine	Peak Heart Rate	30 mg Cocaine	74.9 beats per minute	Standard Error 2.5
n-Acetylcysteine	Peak Heart Rate	60 mg Cocaine	85.4 beats per minute	Standard Error 4.4

Secondary

Peak Ratings of Active, Alert, Energetic on the Visual Analog Scale

Subjects rated their feelings of Active, Alert, Energetic on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both n-acetylcysteine and placebo conditions.