Cocaine DependencePhase 2/3COSTNCT01468012
Imaging the Neurobiology of Behavioral and Medication Treatment for Cocaine Dependence
A Phase 2/3 study testing levodopa carbidopa and entacapone (LCE) in people with Cocaine Dependence, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
The proposed study will look at cocaine dependent individuals and will consist of three consecutive phases: 1) the 2-week outpatient lead-in phase during which behavioral therapy will be administered; 2) the 15-21 day inpatient phase (during which participants will start study medication of levodopa,carbidopa and… Read more about this study
- Who is it for?
- Ages 21 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cocaine Dependence
- What is being tested?
- levodopa carbidopa and entacapone (LCE)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to Dec 2015
- Phase
- Phase 2/3
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adult, age 21-50.
- Meets DSM-IV criteria for current cocaine dependence, supported by a positive urine for cocaine metabolites
- Voluntarily seeking treatment for cocaine dependence
- Absence of other medical or psychiatric disorders that are unstable and would interfere with participation.
- Absence of any suspicious skin changes, suggestive of melanoma, during the full body exam
- Able to give informed consent.
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- Adult, age 21-50.
- No current DSM-IV psychiatric or substance use disorders
- Absence of other medical disorders that are unstable and would interfere with participation.
- Able to give informed consent.
Who cannot join
- Current DSM-IV criteria of other substance use disorders with the exception of nicotine dependence, and mild to moderate alcohol or cannabis abuse or dependence. Alcohol or cannabis abuse or dependence may be included provided that cocaine is the predominant problem, and medical detoxification is not indicated; alcohol and cannabis use are common among cocaine dependent patients and their categorical exclusion would impede recruitment and result in a sample of limited generalizability; secondary analyses will explore whether they exert any moderating effects on the main findings.
- Active psychiatric disorder which might interfere with participation or make participation hazardous, including DSM-IV organic mental disorder, psychotic disorder, bipolar disorder, recurrent severe MDD, OCD, or eating disorder. Participants with depressive disorder (provided that the score on the Hamilton Depression Scale is less than 20) and those with ADHD symptoms may be included, since these are common, often reflect effects of chronic drug use, and may improve with behavioral treatment and cessation or reduction of drug use.
- Unstable medical disorders, or medical disorders that might interfere with study participation, including seizure disorder.
- Significant current suicidal risk or 1 or more suicide attempts within the past year
- Concurrent treatment with psychotropic medications
- Positive serum pregnancy test, lactation, or unwillingness to use a satisfactory method of birth control
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- Baseline systolic BP of > 140 and < 100, diastolic BP > 90 and < 60 and baseline HR greater than 90.
- Any clinically significant heart abnormality or cardiovascular disease
- History of glaucoma
- History of melanoma or current suspicious undiagnosed skin lesions
- History of allergic reaction or adverse reaction to study medications (levodopa/carbidopa/entacapone; methylphenidate; raclopride).
- Metal implants or paramagnetic objects contained within the body which may interfere with the MRI scan as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects" by Shellock
- Lifetime exposure to radiation in the workplace, or history of participation in nuclear medicine procedures, including research protocols
- Individuals who are predominantly left handed. Based on a score <50 on the Edinburg Handed Inventory (E.H.I.).
- Current or recent DSM-IV psychiatric or substance use disorders
- Past history of any major Axis I disorder (e.g., psychotic disorders, bipolar disorder, recurrent major depressive disorder, OCD or eating disorders).
- Unstable medical disorders, or medical disorders that might interfere with study participation.
- Concurrent treatment with psychotropic medications
- Positive serum pregnancy test, lactation, or unwillingness to use a satisfactory method of birth control *
- Baseline systolic BP of > 140 and < 100, diastolic BP > 90 and < 60 and baseline HR greater than 90.
- Any clinically significant heart abnormality or cardiovascular disease
- History of allergic reaction or adverse reaction to study medications (methylphenidate; raclopride).
- Metal implants or paramagnetic objects contained within the body which may interfere with the MRI scan as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects" by Shellock
- Individuals who are predominantly left handed. Based on a score <50 on the Edinburg Handed Inventory (E.H.I.).
Trial locations and contacts
1 site in 1 country.
About this study
The proposed study will look at cocaine dependent individuals and will consist of three consecutive phases: 1) the 2-week outpatient lead-in phase during which behavioral therapy will be administered; 2) the 15-21 day inpatient phase (during which participants will start study medication of levodopa,carbidopa and entacapone (LCE) and will undergo brain imaging and 3) the 24 weeks outpatient treatment trial. The purpose is to see if treatment with LCE may reverse baseline brain deficits and if this change is associated with clinical improvement. Hypothesis is that treatment with LCE, compared to placebo, increases abstinence from cocaine over a 12-week trial in combination with behavioral treatment with voucher incentives.
Read the detailed description
Cocaine dependence remains a serious public health problem; however no clearly effective pharmacological treatments have been identified to date. The investigators hypothesize that identification of subgroups of cocaine-dependent patients will help to develop targeted and more effective treatments. The investigators have observed that 30-40% of cocaine-dependent patients who enter our medication trials achieve abstinence during the lead-in period (the two weeks prior to starting medication). Initial abstinence is strongly predictive of abstinence during the subsequent medication trial. The investigators have also observed that a low dopamine release in the striatum is associated with greater choice of cocaine in volunteers and failure of cocaine-dependent patients to respond to behavioral treatment. The investigators hypothesize that individuals who have difficulties in achieving abstinence have a deficit in dopaminergic functioning and correcting this deficit using dopaminergic medication LCE (levodopa in combination with carbidopa and entacapone) will result in clinical improvement.
The proposed study will consist of three consecutive phases: 1) the 2-week outpatient lead-in phase during which behavioral therapy will be administered; 2) the 15-21 day inpatient phase (during which participants will start study medication and will undergo brain imaging; one PET and two fMRI scan sessions); and 3) the 24 weeks outpatient treatment trial.
Study medication (LCE or placebo) will be administered in a double-blind, placebo controlled manner for one week during inpatient phase followed by 12 weeks of the outpatient trial. During the remaining 12 weeks of the outpatient trial participants will receive therapy only.
The purpose of the lead-in phase is to identify patients who do not achieve abstinence in response to behavioral treatment. Subsequently, two matched subgroups of participants (half who achieved abstinence and half who did not achieve abstinence) will undergo the [11C] raclopride displacement PET brain imaging procedure. This procedure allows the measurement of dopamine release in response to a single dose of methylphenidate, and the investigators will determine if failure to achieve abstinence during the lead-in period is associated low dopamine transmission.
All participants in the proposed study will also undergo a functional MRI with the Motivational Incentive Delay task (fMRI/MID). This task is thought to reflect dopaminergic transmission in the brain-reward system but is safer and more feasible than PET. The investigators hypothesize that fMRI/MID will correlate strongly with results from the PET procedure, thereby suggesting that it also reflects the status of striatal dopamine functioning. In addition, a group of healthy controls will undergo one fMRI scan in order to validate the procedure and to assess if a deficit can be detected in cocaine-dependent participants. Cocaine-dependent participants will undergo two fMRI/MID, one at baseline and another after a week of treatment with LCE to assess if treatment with LCE may reverse baseline deficits and if this change is associated with clinical improvement.
- Conditions
- Cocaine Dependence
- Being tested
- levodopa carbidopa and entacapone (LCE), Placebo
- Keywords
- cocaine dependence, levodopa, carbidopa, entacapone
- 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.
levodopa carbidopa and entacapone (LCE)Drug
400mg/100mg/200mg, twice daily
PlaceboDrug
matched placebo for LCE condition dosed twice daily
| Study group | Role | What they receive |
|---|---|---|
| levodopa carbidopa and entacapone (LCE) | Experimental | 400mg/100mg/200mg, twice daily dosing of levodopa carbidopa and entacapone (LCE) Receives: Drug: levodopa carbidopa and entacapone (LCE) |
| Placebo | Placebo comparator | placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cocaine Urine Toxicology
Abstinence will be assessed by urine toxicology results collected 3x/week during the 24 week trial or for the length of participation
Measured: collected 3x/week for 24 weeks of trial or for the duration of the participants involvement in the study.
Retention in Treatment
The number of participants who completed the 12-week medication phase of the study.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2011 (estimated)
- Study startJul 2014
- Primary completionJul 2014
- Study completionDec 2015
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.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adam Bisaga, New York State Psychiatric Institute
- Investigators
- Adam Bisaga, M.D., Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01468012
- Sponsor's protocol ID
- #6022
- Other IDs
- 6022
- Acronym
- COST
- Status last verified
- May 2018
- First submitted
- 7 Nov 2011
- Last updated
- 22 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging the Neurobiology of Behavioral and Medication Treatment for Cocaine Dependence
- ClinicalTrials.gov ID
- NCT01468012
- Acronym / sponsor ID
- COST / #6022
- Conditions
- Cocaine Dependence
- Keywords
- cocaine dependence, levodopa, carbidopa, entacapone
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Study start
- Jul 2014
- Primary completion
- Jul 2014 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 9 Nov 2011 (estimated)
- Results
- Posted 16 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study will look at cocaine dependent individuals and will consist of three consecutive phases: 1) the 2-week outpatient lead-in phase during which behavioral therapy will be administered; 2) the 15-21 day inpatient phase (during which participants will start study medication of levodopa,carbidopa and entacapone (LCE) and will undergo brain imaging and 3) the 24 weeks outpatient treatment trial. The purpose is to see if treatment with LCE may reverse baseline brain deficits and if this change is associated with clinical improvement. Hypothesis is that treatment with LCE, compared to placebo, increases abstinence from cocaine over a 12-week trial in combination with behavioral treatment with voucher incentives.
Detailed description
Cocaine dependence remains a serious public health problem; however no clearly effective pharmacological treatments have been identified to date. The investigators hypothesize that identification of subgroups of cocaine-dependent patients will help to develop targeted and more effective treatments. The investigators have observed that 30-40% of cocaine-dependent patients who enter our medication trials achieve abstinence during the lead-in period (the two weeks prior to starting medication). Initial abstinence is strongly predictive of abstinence during the subsequent medication trial. The investigators have also observed that a low dopamine release in the striatum is associated with greater choice of cocaine in volunteers and failure of cocaine-dependent patients to respond to behavioral treatment. The investigators hypothesize that individuals who have difficulties in achieving abstinence have a deficit in dopaminergic functioning and correcting this deficit using dopaminergic medication LCE (levodopa in combination with carbidopa and entacapone) will result in clinical improvement.
The proposed study will consist of three consecutive phases: 1) the 2-week outpatient lead-in phase during which behavioral therapy will be administered; 2) the 15-21 day inpatient phase (during which participants will start study medication and will undergo brain imaging; one PET and two fMRI scan sessions); and 3) the 24 weeks outpatient treatment trial.
Study medication (LCE or placebo) will be administered in a double-blind, placebo controlled manner for one week during inpatient phase followed by 12 weeks of the outpatient trial. During the remaining 12 weeks of the outpatient trial participants will receive therapy only.
The purpose of the lead-in phase is to identify patients who do not achieve abstinence in response to behavioral treatment. Subsequently, two matched subgroups of participants (half who achieved abstinence and half who did not achieve abstinence) will undergo the [11C] raclopride displacement PET brain imaging procedure. This procedure allows the measurement of dopamine release in response to a single dose of methylphenidate, and the investigators will determine if failure to achieve abstinence during the lead-in period is associated low dopamine transmission.
All participants in the proposed study will also undergo a functional MRI with the Motivational Incentive Delay task (fMRI/MID). This task is thought to reflect dopaminergic transmission in the brain-reward system but is safer and more feasible than PET. The investigators hypothesize that fMRI/MID will correlate strongly with results from the PET procedure, thereby suggesting that it also reflects the status of striatal dopamine functioning. In addition, a group of healthy controls will undergo one fMRI scan in order to validate the procedure and to assess if a deficit can be detected in cocaine-dependent participants. Cocaine-dependent participants will undergo two fMRI/MID, one at baseline and another after a week of treatment with LCE to assess if treatment with LCE may reverse baseline deficits and if this change is associated with clinical improvement.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| levodopa carbidopa and entacapone (LCE) | Experimental | Drug: levodopa carbidopa and entacapone (LCE)400mg/100mg/200mg, twice daily dosing of levodopa carbidopa and entacapone (LCE) |
| Placebo | Placebo comparator | Drug: Placeboplacebo |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Adult, age 21-50.
- Meets DSM-IV criteria for current cocaine dependence, supported by a positive urine for cocaine metabolites
- Voluntarily seeking treatment for cocaine dependence
- Absence of other medical or psychiatric disorders that are unstable and would interfere with participation.
- Absence of any suspicious skin changes, suggestive of melanoma, during the full body exam
Key exclusion criteria (24 listed)
- Current DSM-IV criteria of other substance use disorders with the exception of nicotine dependence, and mild to moderate alcohol or cannabis abuse or dependence. Alcohol or cannabis abuse or dependence may be included provided that cocaine is the predominant problem, and medical detoxification is not indicated; alcohol and cannabis use are common among cocaine dependent patients and their categorical exclusion would impede recruitment and result in a sample of limited generalizability; secondary analyses will explore whether they exert any moderating effects on the main findings.
- Active psychiatric disorder which might interfere with participation or make participation hazardous, including DSM-IV organic mental disorder, psychotic disorder, bipolar disorder, recurrent severe MDD, OCD, or eating disorder. Participants with depressive disorder (provided that the score on the Hamilton Depression Scale is less than 20) and those with ADHD symptoms may be included, since these are common, often reflect effects of chronic drug use, and may improve with behavioral treatment and cessation or reduction of drug use.
- Unstable medical disorders, or medical disorders that might interfere with study participation, including seizure disorder.
- Significant current suicidal risk or 1 or more suicide attempts within the past year
- Concurrent treatment with psychotropic medications
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 |
|---|---|---|
| levodopa carbidopa and entacapone (LCE)400mg/100mg/200mg, twice daily | Drug | levodopa carbidopa and entacapone (LCE) |
| Placebomatched placebo for LCE condition dosed twice daily | Drug | Placebo |
Primary outcome
Cocaine Urine Toxicology
Time frame: collected 3x/week for 24 weeks of trial or for the duration of the participants involvement in the study.
Abstinence will be assessed by urine toxicology results collected 3x/week during the 24 week trial or for the length of participation
Retention in Treatment
Time frame: 12 weeks
The number of participants who completed the 12-week medication phase of the study.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Adam Bisaga, M.D. principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing levodopa carbidopa and entacapone (LCE) 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 10 inclusion and 24 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 22 May 2018. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 16 Dec 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?
Cocaine Urine Toxicology (time frame: collected 3x/week for 24 weeks of trial or for the duration of the participants involvement in the study.). 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?
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 22 May 2018.