Cocaine DependencePhase 2NCT01790490
Glutamatergic Modulation of Cocaine-related Deficits
A Phase 2 study testing Ketamine 0.41 mg/kg, Ketamine 0.71 mg/kg and Lorazepam 2 mg in people with Cocaine Dependence, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
Cocaine dependence involves problematic neuroadaptations, such as heightened reactivity to cocaine cues, that may be responsive to pharmacological modulation of glutamatergic circuits. Read more about this study
- Who is it for?
- Ages 21 to 52 years
- Conditions the study is for
- Cocaine Dependence
- What is being tested?
- Ketamine 0.41 mg/kg, Ketamine 0.71 mg/kg and Lorazepam 2 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Mar 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 to 52 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Active free-base cocaine dependence (at least 4 days of use over the past month, with at least 1 use per week); if the participant uses through another route (IN, IV), then the FB route is dominant (> 80% of occasions).
- Physically healthy
- No adverse reactions to study medications
- 21-52 years of age
- Normal body weight
- Responsive to drug cues
- Capacity to consent
Who cannot join
- Seeking treatment or abstinence
- DSM IV criteria for substance dependence (other than methamphetamine, cocaine, cannabis, or nicotine), or DSM IV criteria for abuse of ketamine or lorazepam
- DSM-IV criteria for other Axis I psychiatric illness that may make participation hazardous such as schizophrenia, schizoaffective disorder, psychosis NOS, MDD, psychosis secondary to substances, or bipolar disorder
- Delirium, Dementia, Amnesia, Cognitive Disorders, or dissociative disorders
- Current suicide risk or a history of suicide attempt within the past 2 years
- Current use of prescribed psychotropic medication
Show all 12Show fewer
- Pregnancy, nursing, or had a baby within the past 6 mo.
- Heart disease as indicated by history, abnormal ECG, previous cardiac surgery.
- Unstable physical disorders which might make participation hazardous such as end-stage AIDS, hypertension (>140/90), anemia, active hepatitis or other liver disease, or diabetes
- "Bad" reaction/experience with prior exposure to ketamine or lorazepam
- History of significant violence
- First degree relative with a psychotic disorder
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Ketamine on Reducing Cue Reactivity in Cocaine Users
Cocaine dependence involves problematic neuroadaptations, such as heightened reactivity to cocaine cues, that may be responsive to pharmacological modulation of glutamatergic circuits. Despite promising preclinical findings with n-methyl-d-aspartate receptor (NMDAr) modulators, studies with human subjects have been unsuccessful to date. The purpose of this investigation is to examine the effects of the NMDAr antagonist ketamine, recently found to have potent therapeutic effects in humans, on cue-induced craving and impaired motivation for quitting cocaine in cocaine dependent participants, 24-hours post-infusion.
Read the detailed description
In this study, volunteers will undergo a 9 day inpatient trial during which they will receive three counter-balanced infusions (two doses of ketamine and a dose of lorazepam) on three separate days in a within-subject, double-blind, controlled design. Of the various glutamate antagonists available for human use, ketamine will be utilized because its safety profile, pharmacokinetics, and range of tolerable sub-anesthetic dosings have been very well studied. Also, ketamine has shown promise in managing opiate and alcohol use disorders in certain studies, and may therefore be the most likely glutamate antagonist to dampen cue reactivity and increase motivation in cocaine users. If ketamine significantly improves these deficits, this would suggest that the drug should be investigated further for potential utility as a treatment for cocaine dependence.
- Conditions
- Cocaine Dependence
- Being tested
- Ketamine 0.41 mg/kg, Ketamine 0.71 mg/kg, Lorazepam 2 mg
- 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.
Ketamine 0.41 mg/kgDrug
Also called K1
52 minute iv infusion of ketamine 0.41 mg/kg
Ketamine 0.71 mg/kgDrug
Also called K2
52 minute iv infusion of ketamine 0.71 mg/kg. This dose follows K1 in all 3 orderings.
Lorazepam 2 mgDrug
Also called LZP
52 minute infusion of lorazepam 2 mg. This serves as an active control.
| Study group | Role | What they receive |
|---|---|---|
| K1 | Experimental | Ketamine 0.41 mg/kg infused over 52 min (K1) Receives: Drug: Ketamine 0.41 mg/kg |
| K2 | Experimental | Ketamine 0.71 mg/kg infused over 52 min (K2) Receives: Drug: Ketamine 0.71 mg/kg |
| LZP | Experimental | Lorazepam 2 mg infused over 52 minutes (LZP) Receives: Drug: Lorazepam 2 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cue Reactivity
Serial visual analogue scale (VAS) scores for craving elicited by cocaine cue: units on a scale (0-200), high is worse. Scores are obtained at baseline and at 24 hours after the infusion.
Measured: Baseline and 24 hours after infusion
Change in Motivation to Quit
Motivation score obtained from the University of Rhode Island Change Assessment (URICA). Scores are obtained at baseline and at 24 hours after each infusion. The scores are 0-13, with higher scores indicating greater motivation. The analysis is within-subject. Scores included below are means; higher scores represent higher motivation to quit than do lower scores.
Measured: Baseline and 24 hours post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2013 (estimated)
- Study startFeb 2011
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cocaine DependenceStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elias Dakwar, New York State Psychiatric Institute
- Investigators
- Elias Dakwar, MD, Principal investigator, NYSPI/Columbia College of Physicians and SurgeonsCarl Hart, PhD, Study chair, NYSPI/Columbia College of Physicians and Surgeons
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01790490
- Sponsor's protocol ID
- #6162
- Status last verified
- Apr 2019
- First submitted
- 8 Feb 2013
- Last updated
- 30 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Dakwar E, Levin F, Foltin RW, Nunes EV, Hart CL. The effects of subanesthetic ketamine infusions on motivation to quit and cue-induced craving in cocaine-dependent research volunteers. Biol Psychiatry. 2014 Jul 1;76(1):40-6. doi: 10.1016/j.biopsych.2013.08.009. Epub 2013 Sep 12.
PubMed 24035344
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Ketamine on Reducing Cue Reactivity in Cocaine Users
- ClinicalTrials.gov ID
- NCT01790490
- Acronym / sponsor ID
- #6162
- Conditions
- Cocaine Dependence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Study start
- Feb 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 13 Feb 2013 (estimated)
- Results
- Posted 27 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cocaine dependence involves problematic neuroadaptations, such as heightened reactivity to cocaine cues, that may be responsive to pharmacological modulation of glutamatergic circuits. Despite promising preclinical findings with n-methyl-d-aspartate receptor (NMDAr) modulators, studies with human subjects have been unsuccessful to date. The purpose of this investigation is to examine the effects of the NMDAr antagonist ketamine, recently found to have potent therapeutic effects in humans, on cue-induced craving and impaired motivation for quitting cocaine in cocaine dependent participants, 24-hours post-infusion.
Detailed description
In this study, volunteers will undergo a 9 day inpatient trial during which they will receive three counter-balanced infusions (two doses of ketamine and a dose of lorazepam) on three separate days in a within-subject, double-blind, controlled design. Of the various glutamate antagonists available for human use, ketamine will be utilized because its safety profile, pharmacokinetics, and range of tolerable sub-anesthetic dosings have been very well studied. Also, ketamine has shown promise in managing opiate and alcohol use disorders in certain studies, and may therefore be the most likely glutamate antagonist to dampen cue reactivity and increase motivation in cocaine users. If ketamine significantly improves these deficits, this would suggest that the drug should be investigated further for potential utility as a treatment for cocaine dependence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| K1 | Experimental | Drug: Ketamine 0.41 mg/kgKetamine 0.41 mg/kg infused over 52 min (K1) |
| K2 | Experimental | Drug: Ketamine 0.71 mg/kgKetamine 0.71 mg/kg infused over 52 min (K2) |
| LZP | Experimental | Drug: Lorazepam 2 mgLorazepam 2 mg infused over 52 minutes (LZP) |
Who may qualify
- Ages
- 21 to 52 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Active free-base cocaine dependence (at least 4 days of use over the past month, with at least 1 use per week); if the participant uses through another route (IN, IV), then the FB route is dominant (> 80% of occasions).
- Physically healthy
- No adverse reactions to study medications
- 21-52 years of age
- Normal body weight
Key exclusion criteria (12 listed)
- Seeking treatment or abstinence
- DSM IV criteria for substance dependence (other than methamphetamine, cocaine, cannabis, or nicotine), or DSM IV criteria for abuse of ketamine or lorazepam
- DSM-IV criteria for other Axis I psychiatric illness that may make participation hazardous such as schizophrenia, schizoaffective disorder, psychosis NOS, MDD, psychosis secondary to substances, or bipolar disorder
- Delirium, Dementia, Amnesia, Cognitive Disorders, or dissociative disorders
- Current suicide risk or a history of suicide attempt within the past 2 years
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 |
|---|---|---|
| Ketamine 0.41 mg/kgAlso: K152 minute iv infusion of ketamine 0.41 mg/kg | Drug | K1 |
| Ketamine 0.71 mg/kgAlso: K252 minute iv infusion of ketamine 0.71 mg/kg. This dose follows K1 in all 3 orderings. | Drug | K2 |
| Lorazepam 2 mgAlso: LZP52 minute infusion of lorazepam 2 mg. This serves as an active control. | Drug | LZP |
Primary outcome
Change in Cue Reactivity
Time frame: Baseline and 24 hours after infusion
Serial visual analogue scale (VAS) scores for craving elicited by cocaine cue: units on a scale (0-200), high is worse. Scores are obtained at baseline and at 24 hours after the infusion.
Change in Motivation to Quit
Time frame: Baseline and 24 hours post-infusion
Motivation score obtained from the University of Rhode Island Change Assessment (URICA). Scores are obtained at baseline and at 24 hours after each infusion. The scores are 0-13, with higher scores indicating greater motivation. The analysis is within-subject. Scores included below are means; higher scores represent higher motivation to quit than do lower scores.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24035344Dakwar E, Levin F, Foltin RW, Nunes EV, Hart CL. The effects of subanesthetic ketamine infusions on motivation to quit and cue-induced craving in cocaine-dependent research volunteers. Biol Psychiatry. 2014 Jul 1;76(1):40-6. doi: 10.1016/j.biopsych.2013.08.009. Epub 2013 Sep 12.
Related trials for Cocaine Dependence
Recruiting
rTMS and Cognitive-behavioral Therapy for Cocaine Use Disorder
Cocaine Use, Cocaine Dependence
Not yet recruiting
QAIAx - SGI/SI Smart Health Cities: Microcity Enclave Program (Quantum SI/AGI Agency a/k/a AI City Hall Project - UPSTO App Nos. 64/074,526, 64/063,557, 64/105,164, 63/903,181, 63/729,428, 64/125,360; USPTO EO 9424 Assignment ID: 2101042 / ARN: REEL/FRAME: 76481/0026 - OUSD-R&E, Department of War)
Asperger's Disorder, Asperger Disorder
Recruiting
Transcranial Direct Current Stimulation (tDCS) for Treatment of Substance Use Disorder
Cocaine Use Disorder, Cocaine Dependence
RecruitingPhase 1
Safety Study of a Disrupted Adenovirus (Ad) Serotype Cocaine Vaccine for Cocaine-dependent Individuals
Cocaine Dependence
Active, not recruitingPhase 1
AAV8-hCocH for Cocaine Use Disorder
Cocaine Dependence, in Remission
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.
Elias Dakwar, MD principal investigator
NYSPI/Columbia College of Physicians and Surgeons
Carl Hart, PhD study chair
NYSPI/Columbia College of Physicians and Surgeons
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketamine 0.41 mg/kg, Ketamine 0.71 mg/kg and Lorazepam 2 mg in people with Cocaine Dependence, run by New York State Psychiatric Institute at 1 site in United States.
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 7 inclusion and 12 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 30 Apr 2019. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Cue Reactivity (time frame: Baseline and 24 hours after infusion). The study lists 2 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 NCT01790490, 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 30 Apr 2019.