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

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ClinicalTrials.gov Identifier: NCT01471145

Recruitment Status : Completed

First Posted : November 15, 2011

Last Update Posted : October 13, 2014

Sponsor:

Collaborators:

ZonMw: The Netherlands Organisation for Health Research and Development

Alkermes, Inc.

Information provided by (Responsible Party):

Wim van den Brink, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Opioid-Related Disorders Heroin Dependence	Drug: Naltrexone	Phase 4

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	40 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Feasibility, Mechanism of Action and Potential Side Effects of Extended Release Depot Naltrexone in Opioid Dependent Patients
Study Start Date :	January 2013
Actual Primary Completion Date :	October 2014
Actual Study Completion Date :	October 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Naltrexone Naltrexone hydrochloride

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Depot Naltrexone	Drug: Naltrexone naltrexone for extended-release injectable suspension, 380 mg/vial, every 4 weeks or once a month Other Name: Vivitrol

Outcome Measures

Primary Outcome Measures :

Brain functions [ Time Frame: 3 months ]
Brain functions of 20 heroin addicts just before and during a three month extended release naltrexone treatment using both functional MRI and dopamine transporter SPECT, compared to brain functions of 20 healthy controls.

Secondary Outcome Measures :

Feasibility and potential efficacy [ Time Frame: 3 months ]
The feasibility and potential efficacy of extended release naltrexone in a pilot sample of 20 Dutch heroin addicts in terms of (a) the percentage of patients that actually starts treatment when invited and (b) the percentage of 3 months retention.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 55 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

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): NCT01471145

Locations

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Netherlands
Academic Medical Center
Amsterdam, Netherlands, P.O. Box 22660

Sponsors and Collaborators

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

ZonMw: The Netherlands Organisation for Health Research and Development

Alkermes, Inc.

Investigators

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Principal Investigator:	Wim van den Brink, MD PhD	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

More Information

Publications:

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.

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. Epub 2006 Nov 29.

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.

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.

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. Epub 2007 Dec 3.

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

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.

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.

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.

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.

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.

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Responsible Party:	Wim van den Brink, Prof. dr. W. van den Brink, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:	NCT01471145
Other Study ID Numbers:	60-60600-97-301 2011-001890-15 ( EudraCT Number )
First Posted:	November 15, 2011 Key Record Dates
Last Update Posted:	October 13, 2014
Last Verified:	October 2014

Keywords provided by Wim van den Brink, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):


opioid dependence heroin dependence extended release depot naltrexone	functional Magnetic Resonance Imaging dopamine transporter Single Photon Emission Computed Tomography

Additional relevant MeSH terms:

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Opioid-Related Disorders Heroin Dependence Substance-Related Disorders Chemically-Induced Disorders Mental Disorders Naltrexone	Alcohol Deterrents Narcotic Antagonists Physiological Effects of Drugs Sensory System Agents Peripheral Nervous System Agents

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