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

NCT01471145 | Completed Phase 4

• 2 other identifiers: 60-60600-97-3012011-001890-15
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Conditions

Opioid-Related Disorders; Heroin Dependence

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Brain functions

  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.

  3 months

Secondary Outcomes (1)

• Feasibility and potential efficacy

  3 months

Study Arms (1)

Depot Naltrexone

EXPERIMENTAL

Drug: Naltrexone

Interventions

Naltrexone DRUG

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

Also known as: Vivitrol

Depot Naltrexone

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Alkermes, Inc.: collaborator

Study Sites (1)

Academic Medical Center

Amsterdam, P.O. Box 22660, Netherlands

Location

Related Publications (11)

• 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.

  PMID: 9437624 BACKGROUND

• 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.

  PMID: 17137562 BACKGROUND

• 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.

  PMID: 10875899 BACKGROUND

• 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.

  PMID: 21529928 BACKGROUND

• 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.

  PMID: 18056224 BACKGROUND

• 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.

  PMID: 18425938 BACKGROUND

• 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.

  PMID: 20932921 BACKGROUND

• 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.

  PMID: 18674871 BACKGROUND

• 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.

  PMID: 19034737 BACKGROUND

• 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.

  PMID: 18077142 BACKGROUND

• 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.

  PMID: 18823721 BACKGROUND

MeSH Terms

Conditions

Opioid-Related Disorders; Heroin Dependence

Interventions

Naltrexone; vivitrol

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Wim van den Brink, MD PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr. W. van den Brink

Study Record Dates

• First Submitted: November 10, 2011
• First Posted: November 15, 2011
• Study Start: January 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: October 13, 2014

Record last verified: 2014-10

Locations

NL (1)