Neurobiological Adaptations and Pharmacological Interventions in Cocaine Addiction

NCT02626494 | Completed Phase 4 DMC

• 1 other identifier: CoGlu_PUK_ZH_2014_0010
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims at testing for the impact of glutamatergic changes on drug craving in cocaine addiction, and to evaluate the effects of n-acetylcysteine (n-AC) on both glutamate homeostasis and craving using a randomized, double-blind, placebo controlled cross-over design.

Conditions

Cocaine Addiction

Outcome Measures

Primary Outcomes (3)

• Glutamatergic alterations in cocaine users assessed by 1H-MRS as glutamate concentrations in the nucleus accumbens expressed as glutamate ratios in relation to water [glutamate/water]

  \- Changes in basal glutamatergic neurotransmission in the nucleus accumbens in cocaine addiction will be assessed via 1H-MRS.

  It will be assessed in the placebo condition at either the 1.measurement (approximately 1.5h after ingestion of the last dose), on average 2 days after the initial assessment of the subject or at the 2.measurement (in average 14 days after 1.measurement)

• Impact of n-acetylcystein on glutamate homeostasis assessed by 1H-MRS as glutamtate concentrations in the nucleus accumbens expressed as glutamate ratios in relation to water [glutamate/water]

  * The impact of n-AC on glutamatergic neurotransmission in cocaine addiction will be assessed via 1H-MRS.

  The impact of n-AC will be assessed by comparing n-AC and placebo condition, with an average time interval of 14 days between measurements.

• Impact of n-acetylcystein on craving assessed by visual analog scales

  * Craving will be assessed via subjective ratings on visual analog scales * The impact of n-AC will be assessed by comparing craving in cocaine dependent individuals under n-AC and placebo.

  The impact of n-AC will be assessed by comparing n-AC and placebo condition with an average time interval of 2 weeks between measurements.

Secondary Outcomes (1)

• Alterations in frontostriatal networks indicated by connectivity coefficients assessed by functional magnetic resonance imaging

  Alterations in frontostriatal will be assessed by comparing n-AC and placebo condition with an average time interval of 2 weeks.

Study Arms (2)

Cocaine Group

EXPERIMENTAL

n-AC and placebo will be given according to a double-blind, placebo-controlled cross-over design. Subjects receive 4 doses of n-AC/placebo over 2 consecutive days (total dose=4800mg; individual dose=1200mg). Subjects will take the first 2 doses of n-AC/placebo 5 days after the screening assessment (one in the morning, one in the evening), and the last 2 dose 1h prior to scanning, with 12 hours dosing intervals in between. 14 days later n-AC/placebo will be administered analogously as described above. Preparation and blinding of n-AC and placebo capsules will be performed by the Kantonsapotheke Zürich according to the guidelines of Good Manufacturing Practice.

Drug: N-Acetylcystein; Drug: Placebo

Healthy Control Group

ACTIVE COMPARATOR

n-AC and placebo will be given according to a double-blind, placebo-controlled cross-over design. Subjects receive 4 doses of n-AC/placebo over 2 consecutive days (total dose=4800mg; individual dose=1200mg). Subjects will take the first 2 doses of n-AC/placebo 5 days after the screening assessment (one in the morning, one in the evening), and the last 2 dose 1h prior to scanning, with 12 hours dosing intervals in between. 14 days later n-AC/placebo will be administered analogously as described above. Preparation and blinding of n-AC and placebo capsules will be performed by the Kantonsapotheke Zürich according to the guidelines of Good Manufacturing Practice.

Drug: N-Acetylcystein; Drug: Placebo

Interventions

N-Acetylcystein DRUG

n-AC will be given according to a double-blind, placebo-controlled cross-over design. Subjects receive 3 doses of n-AC over 2 consecutive days (total dose=4800mg; individual doses=2x1200mg, 1x2400mg). Subjects will take 2 first doses (à 1200mg) of n-AC 5 days after the screening assessment (one in the morning, one in the evening), and the last dose (2400mg) 1h prior to scanning, with 12 hours dosing intervals in between. Preparation and blinding of n-AC capsules will be performed by the Kantonsapotheke Zürich according to the guidelines of Good Manufacturing Practice.

Cocaine Group; Healthy Control Group

Placebo DRUG

14 days before or after, placebo will be administered analogously as described with n-AC. Placebo will be given according to a double-blind, placebo-controlled cross-over design. Subjects receive 3 doses of placebo over 2 consecutive days (total dose=4800mg; individual doses=2x1200mg, 1x2400mg). Subjects will take 2 first doses (à 1200mg) of placebo 1 day before scanning (one in the morning, one in the evening), and the last dose (2400mg) 1h prior to scanning, with 12 hours dosing intervals in between. Preparation and blinding of placebo capsules will be performed by the Kantonsapotheke Zürich according to the guidelines of Good Manufacturing Practice.

Cocaine Group; Healthy Control Group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Cocaine use disorder vs. no substance use
• Magnetic resonance imaging compatibility

You may not qualify if:

• Regular use of other psychoactive drugs
• Comorbidity of other psychiatric disorders
• Neurological or somatic disease

Sponsors & Collaborators

• Psychiatric University Hospital, Zurich: lead
• Zurich Center for Integrative Human Physiology: collaborator
• Swiss Federal Institute of Technology: collaborator
• Max-Planck-Institut Tübingen: collaborator

Study Sites (1)

Psychiatric University Hospital, Zurich

Zurich, 8001, Switzerland

Location

Related Publications (1)

• Engeli EJE, Preller KH, Rieser NM, Klar J, Staempfli P, Hulka LM, Kirschner M, Seifritz E, Herdener M. N-acetylcysteine reduces prefrontal reactivity to cocaine cues in individuals with cocaine use disorder. Front Psychiatry. 2025 Feb 27;15:1489194. doi: 10.3389/fpsyt.2024.1489194. eCollection 2024.

  PMID: 40083914 DERIVED

MeSH Terms

Conditions

Cocaine-Related Disorders

Condition Hierarchy (Ancestors)

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

Study Officials

• Marcus Herdener, MD

  Center for Addicitve Disorders

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. med Marcus Herdener

Study Record Dates

• First Submitted: May 20, 2015
• First Posted: December 10, 2015
• Study Start: March 1, 2015
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: May 1, 2017

Record last verified: 2017-04

Locations

CH (1)