Depot Naltrexone Mechanism of Action in Heroin Dependent Patients Using fMRI and SPECT

NCT ID: NCT01471145

Last Updated: 2014-10-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-31

Study Completion Date

2014-10-31

Brief Summary

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The aim of this project is to study brain functions of 20 heroin addicts (compared to brain functions of 20 healthy controls) just before and during a three month extended release naltrexone treatment using functional MRI and dopamine transporter SPECT.

The following hypotheses are tested:

* XRNT modulates the fMRI response to drug cues in predetermined brain regions.
* The expression of striatal transporters (assessed with SPECT) will decrease after a three-month course of extended release naltrexone

Detailed Description

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Heroin dependence is a quintessential international health problem, with a significant prevalence. Drug free treatments, including pharmacologically supported interventions using oral naltrexone, have not been very successful, mainly due to low compliance. The recent introduction of Vivitrol®, consisting of monthly injections, may create new opportunities. Vivitrol® is an innovative treatment delivery method that blocks the rewarding effects of heroin.

Conditions

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Opioid-Related Disorders Heroin Dependence

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Depot Naltrexone

Group Type EXPERIMENTAL

Naltrexone

Intervention Type DRUG

naltrexone for extended-release injectable suspension, 380 mg/vial, every 4 weeks or once a month

Interventions

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Naltrexone

naltrexone for extended-release injectable suspension, 380 mg/vial, every 4 weeks or once a month

Intervention Type DRUG

Other Intervention Names

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Vivitrol

Eligibility Criteria

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Inclusion Criteria

* Heroin dependent patients: have a diagnosis of opioid dependence according to DSM-IV criteria, heroin as primary drug of abuse and inhalation as primary route of administration.
* Healthy controls: no diagnosis of substance dependence, no current psychotropic medication. Care will be taken to match controls for gender, age, smoking status, IQ and handedness.

Exclusion Criteria

* Age below 18 or over 55
* Medical contraindications for XRNT or MRI (Langleben 2006; Langleben, Ruparel et al. 2008). Briefly, the former include candidates with known hypersensitivity to naltrexone,PLG (poly-lactide-coglycolide), carboxymethylcellulose, or any other components of the Vivitrol® diluent, hepatic or renal disease, chronic pain syndromes, female subjects who are pregnant or lactating, or are of child bearing potential and are not using an acceptable method of birth control. MRI contraindications include chronic medical (neurological, cardiovascular, infectious, metabolic, etc) conditions that may affect the brain morphology and/or activity and indwelling foreign metallic or magnetically sensitive objects and devices, such as shrapnel, pacemakers, orthopaedic fixation devices or vascular stents
* Presence of disorders precluding normal perception of visual and auditory stimuli, such as color blindness, deafness, severe myopia, etc.
* Patients with a history of or current psychosis or current major depressive disorder with suicidal ideation
* Patients who are being treated under forced treatment conditions
* History or evidence of disorders that may affect cerebral function or circulation, such as diabetes and other metabolic disorders, encephalopathy, cardiovascular or cerebrovascular disease, history of head trauma with depressed skull fracture or prolonged loss of consciousness and history of brain surgery
* Female subjects: women who are pregnant or breast-feeding
* Current psychotropic medication
* Use of any prescription medications that could affect alertness or the circulatory system
* IQ \< 70
* Naltrexone use within the past 6 months
* Baseline aspartate aminotransferase or alanine aminotransferase more than three times the upper limit of normal
* Patients with no intention to be opioid-free for a minimum of 7 days before starting XRNT treatment
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role collaborator

Alkermes, Inc.

INDUSTRY

Sponsor Role collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role lead

Responsible Party

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Wim van den Brink

Prof. dr. W. van den Brink

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Wim van den Brink, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Locations

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Academic Medical Center

Amsterdam, , Netherlands

Site Status

Countries

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Netherlands

References

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Cornish JW, Metzger D, Woody GE, Wilson D, McLellan AT, Vandergrift B, O'Brien CP. Naltrexone pharmacotherapy for opioid dependent federal probationers. J Subst Abuse Treat. 1997 Nov-Dec;14(6):529-34. doi: 10.1016/s0740-5472(97)00020-2.

Reference Type BACKGROUND
PMID: 9437624 (View on PubMed)

de Geus EJ, van't Ent D, Wolfensberger SP, Heutink P, Hoogendijk WJ, Boomsma DI, Veltman DJ. Intrapair differences in hippocampal volume in monozygotic twins discordant for the risk for anxiety and depression. Biol Psychiatry. 2007 May 1;61(9):1062-71. doi: 10.1016/j.biopsych.2006.07.026. Epub 2006 Nov 29.

Reference Type BACKGROUND
PMID: 17137562 (View on PubMed)

Knutson B, Westdorp A, Kaiser E, Hommer D. FMRI visualization of brain activity during a monetary incentive delay task. Neuroimage. 2000 Jul;12(1):20-7. doi: 10.1006/nimg.2000.0593.

Reference Type BACKGROUND
PMID: 10875899 (View on PubMed)

Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011 Apr 30;377(9776):1506-13. doi: 10.1016/S0140-6736(11)60358-9.

Reference Type BACKGROUND
PMID: 21529928 (View on PubMed)

Langleben DD, Ruparel K, Elman I, Busch-Winokur S, Pratiwadi R, Loughead J, O'Brien CP, Childress AR. Acute effect of methadone maintenance dose on brain FMRI response to heroin-related cues. Am J Psychiatry. 2008 Mar;165(3):390-4. doi: 10.1176/appi.ajp.2007.07010070. Epub 2007 Dec 3.

Reference Type BACKGROUND
PMID: 18056224 (View on PubMed)

Lobmaier P, Kornor H, Kunoe N, Bjorndal A. Sustained-release naltrexone for opioid dependence. Cochrane Database Syst Rev. 2008 Apr 16;2008(2):CD006140. doi: 10.1002/14651858.CD006140.pub2.

Reference Type BACKGROUND
PMID: 18425938 (View on PubMed)

Luijten M, Veltman DJ, van den Brink W, Hester R, Field M, Smits M, Franken IH. Neurobiological substrate of smoking-related attentional bias. Neuroimage. 2011 Feb 1;54(3):2374-81. doi: 10.1016/j.neuroimage.2010.09.064. Epub 2010 Oct 13.

Reference Type BACKGROUND
PMID: 20932921 (View on PubMed)

Suh JJ, Langleben DD, Ehrman RN, Hakun JG, Wang Z, Li Y, Busch SI, O'Brien CP, Childress AR. Low prefrontal perfusion linked to depression symptoms in methadone-maintained opiate-dependent patients. Drug Alcohol Depend. 2009 Jan 1;99(1-3):11-7. doi: 10.1016/j.drugalcdep.2008.06.007. Epub 2008 Jul 31.

Reference Type BACKGROUND
PMID: 18674871 (View on PubMed)

Suh JJ, Pettinati HM, Kampman KM, O'Brien CP. Gender differences in predictors of treatment attrition with high dose naltrexone in cocaine and alcohol dependence. Am J Addict. 2008 Nov-Dec;17(6):463-8. doi: 10.1080/10550490802409074.

Reference Type BACKGROUND
PMID: 19034737 (View on PubMed)

Zijlstra F, Booij J, van den Brink W, Franken IH. Striatal dopamine D2 receptor binding and dopamine release during cue-elicited craving in recently abstinent opiate-dependent males. Eur Neuropsychopharmacol. 2008 Apr;18(4):262-70. doi: 10.1016/j.euroneuro.2007.11.002.

Reference Type BACKGROUND
PMID: 18077142 (View on PubMed)

Zijlstra F, Veltman DJ, Booij J, van den Brink W, Franken IH. Neurobiological substrates of cue-elicited craving and anhedonia in recently abstinent opioid-dependent males. Drug Alcohol Depend. 2009 Jan 1;99(1-3):183-92. doi: 10.1016/j.drugalcdep.2008.07.012. Epub 2008 Sep 26.

Reference Type BACKGROUND
PMID: 18823721 (View on PubMed)

Other Identifiers

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2011-001890-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

60-60600-97-301

Identifier Type: -

Identifier Source: org_study_id

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