Cocaine DependencePhase 4RAPIDNCT02134002
A PET Exploration of the Mechanism of Action of Dopamine Beta-hydroxylase Inhibition in Cocaine Addicts
A Phase 4 study testing Disulfiram in people with Cocaine Dependence, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
This study represents a randomized, double blind placebo-controlled trial. Thirty cocaine dependant patients will be included in this study during their hospitalization for withdrawal. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Cocaine Dependence
- What is being tested?
- Disulfiram
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2014to Dec 2016
- 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 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- men aged 18 years ans less than or equal 65
- diagnosis of cocaine dependence according to DSM IV
- hospitalization for cocaine withdrawal
- ability to understand and give informed consent orally ans in writing
- affiliation to a social security
- patient with a normal ECG and normal blood pressure
Who cannot join
- Psychiatric comorbidity : psychotic disorder, manic episode , major depressive current , high suicide risk , assessed by structured interview of the Mini International Neuropsychiatric Interview
- Neurological histories: neurological deficit focused, organic cerebral disorder , epilepsy, dementia
- Severe hepatic insufficiency
- Severe renal insufficiency
- Severe respiratory
- Diabetes
Show all 26Show fewer
- Hypersensitivity disulfiram or any of the other components
- Neuropsychological disorder
- Preexisting cardiovascular disorders
- Hypersensitivity to methylphenidate or any of the excipients
- Hyperthyroidism or thyrotoxicosis
- Glaucoma
- Pheochromocytoma
- Preexisting cerebrovascular disorders
- Patient presenting an allergy to the wheat
- HIV or HCV seropositivity
- Family or personal history of motor tics, and syndrome of Gilles Tourette
- Any disorder that may interfere with adherence to treatment
- Pharmacological treatment interfering with catecholamines
- Participation in another clinical trial or exclusion period of a previous clinical trial
- Contraindications to magnetic resonance imaging
- People under placement measure
- Hypersensitivity to any component of NIQUITIN
- Skin disorder that may interfere with the use of a transdermal patch
- Patient under treatment with irreversible inhibitors of mono- amine oxidase inhibitors (MAOIs ) , and for at least 14 days following the stop of the treatment by an IMAO.
- Diagnosis or history of bipolar disorders (affective ) episodic and severe ( type 1 )"
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dopamine Beta-hydroxylase Inhibition Induced Blunting of Dopaminergic Response to Psychostimulant Administration. A PET Exploration of the Mechanism of Action of a New Therapeutic Strategy in Cocaine Addicts
This study represents a randomized, double blind placebo-controlled trial. Thirty cocaine dependant patients will be included in this study during their hospitalization for withdrawal. After the inclusion visit, they will be randomized to receive disulfiram 250 mg/day or placebo over the 15 days of their hospitalization. Main outcome criteria will be evaluated during two TEP imaging sessions with 11Craclopride, before and after stimulation by methylphenidate, 8 to 15 days after randomization.
Read the detailed description
"Dopamine beta-hydroxylase (DHB) inhibition represents a promising approach to treating cocaine dependence. DBH is the enzyme responsible for hydroxylation of dopamine into noradrenaline. Its inhibition suppresses noradrenaline secretion. In animal studies, the efficacy of DBH inhibition in psychostimulants use could be linked to a reduced dopaminergic response, possibly in association with post synaptic dopaminergic receptor hypersensitivity. In humans, the clinical efficacy of DBH inhibition, in particular following disulfiram administration, is in the process of being established. However, its particular mode of action remains unclear: some publications suggest an increased aversive reaction to cocaine, whereas others report decreased positive effects. To date, the impact of DBH inhibition on dopaminergic response to psychostimulants has yet to be studied in humans.
This study represents a randomized, double blind placebo-controlled trial. Thirty cocaine dependant patients will be included in this study during their hospitalization for withdrawal. After the inclusion visit, they will be randomized to receive disulfiram 250 mg/day or placebo over the 15 days of their hospitalization. Main outcome criteria will be evaluated during two TEP imaging sessions with 11Craclopride, before and after stimulation by methylphenidate, 8 to 15 days after randomization. The main outcome criterion will be the variations in linkage rates of 11Craclopride in the nucleus accumbens between baseline TEP measurement and TEP measurement following administration of 20 mg of methylphenidate.
The primary objective of this trial is to show that in abstinent cocaine patients, DBH inhibition by disulfiram induces reduced dopaminergic response following methylphenidate administration. The secondary objectives of this trial are:
- to show that methylphenidate stimulation induces less craving and more aversive responses in the disulfiram vs placebo condition;
- to show that DBH inhibition by disulfiram elevates D2 dopaminergic receptor availability (in the absence of methylphenidate stimulation);
- to show that the availability of D2 dopaminergic receptors (in the absence of methylphenidate stimulation) is linked to DBH activity;
- to confirm that in abstinent cocaine patients, disulfiram reduces DBH activity vs placebo;
- to confirm that subjects with weak DBH activity have more aversive reactions to cocaine.
Currently, disulfiram is the only drug on the market that inhibits DBH. Another more specific DBH inhibitor is currently under development. It is possible that other inhibitors could soon be developed by the pharmaceutical industry in the area of psychoactive drug addiction or other psychiatric or somatic disorders. The development of this new therapeutic approach requires a better understanding of its action mechanism.
"
- Conditions
- Cocaine Dependence
- Being tested
- Disulfiram, Placebo
- Keywords
- cocaine, disulfiram, beta-dopamine hydroxylase
- 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.
DisulfiramDrug
Thirty cocaine dependant patients will be included in this study during their hospitalization for withdrawal. After the inclusion visit, they will be randomized to receive disulfiram 250 mg/day or placebo over the 15 days of their hospitalization.
PlaceboDrug
Also called Placebo of disulfiram
Thirty cocaine dependant patients will be included in this study during their hospitalization for withdrawal. After the inclusion visit, they will be randomized to receive disulfiram 250 mg/day or placebo over the 15 days of their hospitalization.
| Study group | Role | What they receive |
|---|---|---|
| Disulfiram | Experimental | disulfiram 250 mg/day Receives: Drug: Disulfiram |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Variations in linkage rates of 11Craclopride in the nucleus accumbens between baseline TEP measurement and TEP measurement following administration of 20 mg of methylphenidate.
The primary objective of this trial is to show that in abstinent cocaine patients, DBH inhibition by disulfiram induces reduced dopaminergic response following methylphenidate administration.
Measured: up to 15 days after randomization
Secondary outcomes (3)
DBH activity as measured directly, and indirectly by the DHPG / DOPAC report.
Measured: Before and after stimulation by methylphenidate, 8 to 15 days after randomization.
Measurement of craving in cocaine by a simple Likert scale.
Measured: Before and after stimulation by methylphenidate, 8 to 15 days after randomization.
Measure of aversion to cocaine by a simple Likert scale.
Measured: before and after stimulation by methylphenidate, 8 to 15 days after randomization.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2014 (estimated)
- Study startJun 2014
- Primary completionApr 2016 (estimated)
- Study completionDec 2016 (estimated)
Why it stopped: Too selective recrutment criteria, none eligible patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cocaine DependenceStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- National Research Agency, France
- Responsible party
- Sponsor
- Investigators
- Henri-Jean AUBIN, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02134002
- Sponsor's protocol ID
- P121006
- Acronym
- RAPID
- Status last verified
- Dec 2014
- First submitted
- 7 May 2014
- Last updated
- 9 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dopamine Beta-hydroxylase Inhibition Induced Blunting of Dopaminergic Response to Psychostimulant Administration. A PET Exploration of the Mechanism of Action of a New Therapeutic Strategy in Cocaine Addicts
- ClinicalTrials.gov ID
- NCT02134002
- Acronym / sponsor ID
- RAPID / P121006
- Conditions
- Cocaine Dependence
- Keywords
- cocaine, disulfiram, beta-dopamine hydroxylase
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Too selective recrutment criteria, none eligible patients
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- National Research Agency, France
- Study start
- Jun 2014
- Primary completion
- Apr 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 8 May 2014 (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 represents a randomized, double blind placebo-controlled trial. Thirty cocaine dependant patients will be included in this study during their hospitalization for withdrawal. After the inclusion visit, they will be randomized to receive disulfiram 250 mg/day or placebo over the 15 days of their hospitalization. Main outcome criteria will be evaluated during two TEP imaging sessions with 11Craclopride, before and after stimulation by methylphenidate, 8 to 15 days after randomization.
Detailed description
"Dopamine beta-hydroxylase (DHB) inhibition represents a promising approach to treating cocaine dependence. DBH is the enzyme responsible for hydroxylation of dopamine into noradrenaline. Its inhibition suppresses noradrenaline secretion. In animal studies, the efficacy of DBH inhibition in psychostimulants use could be linked to a reduced dopaminergic response, possibly in association with post synaptic dopaminergic receptor hypersensitivity. In humans, the clinical efficacy of DBH inhibition, in particular following disulfiram administration, is in the process of being established. However, its particular mode of action remains unclear: some publications suggest an increased aversive reaction to cocaine, whereas others report decreased positive effects. To date, the impact of DBH inhibition on dopaminergic response to psychostimulants has yet to be studied in humans.
This study represents a randomized, double blind placebo-controlled trial. Thirty cocaine dependant patients will be included in this study during their hospitalization for withdrawal. After the inclusion visit, they will be randomized to receive disulfiram 250 mg/day or placebo over the 15 days of their hospitalization. Main outcome criteria will be evaluated during two TEP imaging sessions with 11Craclopride, before and after stimulation by methylphenidate, 8 to 15 days after randomization. The main outcome criterion will be the variations in linkage rates of 11Craclopride in the nucleus accumbens between baseline TEP measurement and TEP measurement following administration of 20 mg of methylphenidate.
The primary objective of this trial is to show that in abstinent cocaine patients, DBH inhibition by disulfiram induces reduced dopaminergic response following methylphenidate administration. The secondary objectives of this trial are:
- to show that methylphenidate stimulation induces less craving and more aversive responses in the disulfiram vs placebo condition;
- to show that DBH inhibition by disulfiram elevates D2 dopaminergic receptor availability (in the absence of methylphenidate stimulation);
- to show that the availability of D2 dopaminergic receptors (in the absence of methylphenidate stimulation) is linked to DBH activity;
- to confirm that in abstinent cocaine patients, disulfiram reduces DBH activity vs placebo;
- to confirm that subjects with weak DBH activity have more aversive reactions to cocaine.
Currently, disulfiram is the only drug on the market that inhibits DBH. Another more specific DBH inhibitor is currently under development. It is possible that other inhibitors could soon be developed by the pharmaceutical industry in the area of psychoactive drug addiction or other psychiatric or somatic disorders. The development of this new therapeutic approach requires a better understanding of its action mechanism.
"
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Disulfiram | Experimental | Drug: Disulfiramdisulfiram 250 mg/day |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- men aged 18 years ans less than or equal 65
- diagnosis of cocaine dependence according to DSM IV
- hospitalization for cocaine withdrawal
- ability to understand and give informed consent orally ans in writing
- affiliation to a social security
Key exclusion criteria (26 listed)
- Psychiatric comorbidity : psychotic disorder, manic episode , major depressive current , high suicide risk , assessed by structured interview of the Mini International Neuropsychiatric Interview
- Neurological histories: neurological deficit focused, organic cerebral disorder , epilepsy, dementia
- Severe hepatic insufficiency
- Severe renal insufficiency
- Severe respiratory
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 |
|---|---|---|
| DisulfiramThirty cocaine dependant patients will be included in this study during their hospitalization for withdrawal. After the inclusion visit, they will be randomized to receive disulfiram 250 mg/day or placebo over the 15 days of their hospitalization. | Drug | Disulfiram |
| PlaceboAlso: Placebo of disulfiramThirty cocaine dependant patients will be included in this study during their hospitalization for withdrawal. After the inclusion visit, they will be randomized to receive disulfiram 250 mg/day or placebo over the 15 days of their hospitalization. | Drug | Placebo |
Primary outcome
Variations in linkage rates of 11Craclopride in the nucleus accumbens between baseline TEP measurement and TEP measurement following administration of 20 mg of methylphenidate.
Time frame: up to 15 days after randomization
The primary objective of this trial is to show that in abstinent cocaine patients, DBH inhibition by disulfiram induces reduced dopaminergic response following methylphenidate administration.
3 secondary outcomes
DBH activity as measured directly, and indirectly by the DHPG / DOPAC report.
Time frame: Before and after stimulation by methylphenidate, 8 to 15 days after randomization.
Measurement of craving in cocaine by a simple Likert scale.
Time frame: Before and after stimulation by methylphenidate, 8 to 15 days after randomization.
Measure of aversion to cocaine by a simple Likert scale.
Time frame: before and after stimulation by methylphenidate, 8 to 15 days after randomization.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2014.
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.
Henri-Jean AUBIN, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
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 Disulfiram in people with Cocaine Dependence, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 6 inclusion and 26 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: withdrawn, as of the sponsor's last update on 9 Dec 2014. 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 France. 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 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 was withdrawn before enrolling participants, so there are no results.
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?
Variations in linkage rates of 11Craclopride in the nucleus accumbens between baseline TEP measurement and TEP measurement following administration of 20 mg of methylphenidate. (time frame: up to 15 days after randomization). 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 9 Dec 2014.