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Trial record 13 of 46 for:    disulfiram

A PET Exploration of the Mechanism of Action of Dopamine Beta-hydroxylase Inhibition in Cocaine Addicts (RAPID)

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ClinicalTrials.gov Identifier: NCT02134002
Recruitment Status : Withdrawn (Too selective recrutment criteria, none eligible patients)
First Posted : May 8, 2014
Last Update Posted : December 9, 2014
Sponsor:
Collaborator:
National Research Agency, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Cocaine Dependence Drug: Disulfiram Drug: Placebo Phase 4

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:

  1. to show that methylphenidate stimulation induces less craving and more aversive responses in the disulfiram vs placebo condition;
  2. to show that DBH inhibition by disulfiram elevates D2 dopaminergic receptor availability (in the absence of methylphenidate stimulation);
  3. to show that the availability of D2 dopaminergic receptors (in the absence of methylphenidate stimulation) is linked to DBH activity;
  4. to confirm that in abstinent cocaine patients, disulfiram reduces DBH activity vs placebo;
  5. 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.

"


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : June 2014
Estimated Primary Completion Date : April 2016
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Disulfiram
disulfiram 250 mg/day
Drug: 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.

Placebo Comparator: Placebo
Placebo
Drug: Placebo
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.
Other Name: Placebo of disulfiram




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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. ]
  2. Measurement of craving in cocaine by a simple Likert scale. [ Time Frame: Before and after stimulation by methylphenidate, 8 to 15 days after randomization. ]
  3. Measure of aversion to cocaine by a simple Likert scale. [ Time Frame: before and after stimulation by methylphenidate, 8 to 15 days after randomization. ]


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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 )"

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02134002


Locations
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France
Paul Brousse Hospital
Villejuif, France, 94804
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
National Research Agency, France
Investigators
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Principal Investigator: Henri-Jean AUBIN, MD, PhD Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02134002     History of Changes
Other Study ID Numbers: P121006
First Posted: May 8, 2014    Key Record Dates
Last Update Posted: December 9, 2014
Last Verified: December 2014
Keywords provided by Assistance Publique - Hôpitaux de Paris:
cocaine
disulfiram
beta-dopamine hydroxylase
Additional relevant MeSH terms:
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Disulfiram
Cocaine-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Dopamine
Cocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Cardiotonic Agents
Sympathomimetics
Autonomic Agents
Protective Agents
Alcohol Deterrents
Acetaldehyde Dehydrogenase Inhibitors
Enzyme Inhibitors