Cocaine AddictionPhase 4CoGluNCT02626494
Neurobiological Adaptations and Pharmacological Interventions in Cocaine Addiction
A Phase 4 study testing N-Acetylcystein in people with Cocaine Addiction, run by Psychiatric University Hospital, Zurich at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cocaine Addiction
- What is being tested?
- N-Acetylcystein
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 71 participants
- Where
- 1 siteSwitzerland
- Study dates
- Mar 2015to Mar 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Cocaine use disorder vs. no substance use
- Magnetic resonance imaging compatibility
Who cannot join
- Regular use of other psychoactive drugs
- Comorbidity of other psychiatric disorders
- Neurological or somatic disease
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Neurobiological Adaptations and Pharmacological Interventions in Cocaine Addiction: The Role of Glutamate
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.
Read the detailed description
Cocaine addiction is a devastating disorder with potentially harmful psychological, physical and social consequences. Despite its clinical importance, there is currently no approved pharmacological treatment available for cocaine addiction. However, preclinical research has recently identified potentially promising targets for pharmacotherapeutic approaches mainly based on advances in the understanding of neuroplastic alterations associated with repeated cocaine administration in animals.
Preclinical animal models revealed that chronic administration of cocaine leads to decreased basal levels of glutamate within the nucleus accumbens a key region of the neural reward circuitry; in turn, the reinstatement of drug seeking results in enhanced glutamatergic transmission. However, little is known about similar changes in humans, and about their functional role for addictive behavior, mainly due to methodological restrictions. The investigators thus aim to examine the changes associated with chronic cocaine use on glutamate homeostasis in humans using a newly developed proton magnetic resonance spectroscopy (1H-MRS) protocol. This method allows for the quantification of brain metabolites such as glutamate in specific regions of the human brain even within small subcortical volumes of interest such as the nucleus accumbens that have been hitherto difficult to assess.
Interestingly, the administration of n-AC restored the glutamate homeostasis in rats and reduced their drug reinstatement behavior. Therefore, the present study aims at investigating if a pharmacological challenge of n-AC influences glutamate homeostasis in humans and whether these possible modulations are linked to cocaine craving.
Power analyses to identify the sample size of this study, were done with a focus on 1H-MRS, the most critical procedure in this context within our project. Assuming a mean conservative effect size of d=0.80, an α-error probability of 5%, and a conservative power estimation of 80% and considering a drop-out rate of about 30%, investigators plan to measure 30 cocaine dependent patients and 30 healthy controls.
Imaging data of low quality (e.g. due to movement artifacts) will be excluded. If imaging data has to be excluded or if participants do not finish the experiment, the investigators will additionally recruit more participants in order to assess the planned sample size.
Throughout the duration of the entire study, the conductance of pre-defined key processes will constantly be monitored by an independent monitor in specified visit intervals to ensure that the study is conducted in accordance with the approved protocol, good clinical practice, and the applicable regulatory requirement in order to protect the rights and well-being of study participants and integrity of data.
- Conditions
- Cocaine Addiction
- Being tested
- N-Acetylcystein, Placebo
- Medical subject headings
- Cocaine-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-AcetylcysteinDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: N-Acetylcystein; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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 networks will be assessed via magnetic resonance imaging.
Measured: Alterations in frontostriatal will be assessed by comparing n-AC and placebo condition with an average time interval of 2 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2015 (estimated)
- Study startMar 2015
- Primary completionMar 2017
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cocaine AddictionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Psychiatric University Hospital, Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Zurich Center for Integrative Human Physiology, Swiss Federal Institute of Technology, Max-Planck-Institut Tübingen
- Responsible party
- Principal investigator, Dr. med. Marcus Herdener, Psychiatric University Hospital, Zurich
- Investigators
- Marcus Herdener, MD, Principal investigator, Center for Addicitve Disorders
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02626494
- Sponsor's protocol ID
- CoGlu_PUK_ZH_2014_0010
- Acronym
- CoGlu
- Status last verified
- Apr 2017
- First submitted
- 20 May 2015
- Last updated
- 1 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 40083914
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurobiological Adaptations and Pharmacological Interventions in Cocaine Addiction: The Role of Glutamate
- ClinicalTrials.gov ID
- NCT02626494
- Acronym / sponsor ID
- CoGlu / CoGlu_PUK_ZH_2014_0010
- Conditions
- Cocaine Addiction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Psychiatric University Hospital, ZurichUniversity, hospital or other
- Collaborators
- Zurich Center for Integrative Human Physiology, Swiss Federal Institute of Technology, Max-Planck-Institut Tübingen
- Study start
- Mar 2015
- Primary completion
- Mar 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 10 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Cocaine addiction is a devastating disorder with potentially harmful psychological, physical and social consequences. Despite its clinical importance, there is currently no approved pharmacological treatment available for cocaine addiction. However, preclinical research has recently identified potentially promising targets for pharmacotherapeutic approaches mainly based on advances in the understanding of neuroplastic alterations associated with repeated cocaine administration in animals.
Preclinical animal models revealed that chronic administration of cocaine leads to decreased basal levels of glutamate within the nucleus accumbens a key region of the neural reward circuitry; in turn, the reinstatement of drug seeking results in enhanced glutamatergic transmission. However, little is known about similar changes in humans, and about their functional role for addictive behavior, mainly due to methodological restrictions. The investigators thus aim to examine the changes associated with chronic cocaine use on glutamate homeostasis in humans using a newly developed proton magnetic resonance spectroscopy (1H-MRS) protocol. This method allows for the quantification of brain metabolites such as glutamate in specific regions of the human brain even within small subcortical volumes of interest such as the nucleus accumbens that have been hitherto difficult to assess.
Interestingly, the administration of n-AC restored the glutamate homeostasis in rats and reduced their drug reinstatement behavior. Therefore, the present study aims at investigating if a pharmacological challenge of n-AC influences glutamate homeostasis in humans and whether these possible modulations are linked to cocaine craving.
Power analyses to identify the sample size of this study, were done with a focus on 1H-MRS, the most critical procedure in this context within our project. Assuming a mean conservative effect size of d=0.80, an α-error probability of 5%, and a conservative power estimation of 80% and considering a drop-out rate of about 30%, investigators plan to measure 30 cocaine dependent patients and 30 healthy controls.
Imaging data of low quality (e.g. due to movement artifacts) will be excluded. If imaging data has to be excluded or if participants do not finish the experiment, the investigators will additionally recruit more participants in order to assess the planned sample size.
Throughout the duration of the entire study, the conductance of pre-defined key processes will constantly be monitored by an independent monitor in specified visit intervals to ensure that the study is conducted in accordance with the approved protocol, good clinical practice, and the applicable regulatory requirement in order to protect the rights and well-being of study participants and integrity of data.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cocaine Group | Experimental | Drug: N-Acetylcystein, Drug: Placebon-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. |
| Healthy Control Group | Active comparator | Drug: N-Acetylcystein, Drug: Placebon-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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Cocaine use disorder vs. no substance use
- Magnetic resonance imaging compatibility
Key exclusion criteria (3 listed)
- Regular use of other psychoactive drugs
- Comorbidity of other psychiatric disorders
- Neurological or somatic disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-Acetylcysteinn-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. | Drug | Cocaine Group, Healthy Control Group |
| Placebo14 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. | Drug | Cocaine Group, Healthy Control Group |
Primary outcome
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]
Time frame: 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)
- Changes in basal glutamatergic neurotransmission in the nucleus accumbens in cocaine addiction will be assessed via 1H-MRS.
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]
Time frame: 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.
* The impact of n-AC on glutamatergic neurotransmission in cocaine addiction will be assessed via 1H-MRS.
Impact of n-acetylcystein on craving assessed by visual analog scales
Time frame: 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.
* 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.
1 secondary outcome
Alterations in frontostriatal networks indicated by connectivity coefficients assessed by functional magnetic resonance imaging
Time frame: Alterations in frontostriatal will be assessed by comparing n-AC and placebo condition with an average time interval of 2 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2017.
- Derived from this study: PubMed 40083914Engeli 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marcus Herdener, MD principal investigator
Center for Addicitve Disorders
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing N-Acetylcystein in people with Cocaine Addiction, run by Psychiatric University Hospital, Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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] (time frame: 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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02626494, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2017.