This application proposes to conduct a phase II randomized, double blind, placebo-controlled trial of Iofexidine to prevent stress related opiate relapse in naltrexone treated opioid addicted individuals. Stress is known to increase drug craving and risk of relapse to drugs. Lofexidine, an alpha-2-adrenergic agonist, has been shown to attenuate stress-induced reinstatement of opiate seeking behavior in heroin dependent laboratory animals. In a recently completed 8-week pilot safety and efficacy study with 25 opioid dependent individuals seeking naltrexone (Ntx), we found the combination of Iofexidine (Lof) and naltrexone (Ntx) to be well tolerated. Individuals receiving naltrexone-lofexidine (Lof/Ntx) were significantly more likely to stay abstinent from opiates and were significantly more compliant with naltrexone treatment as compared to naltrexone-placebo (Pla/Ntx) subjects. In light of these promising preliminary data, we propose a 4-year clinical trial that will recruit 120 opioid dependent individuals immediately following opioid detoxification to participate in a randomized, double blind, placebo-controlled 12-week treatment study. The following specific aims will be addressed: (1) To evaluate the safety of Iofexidine in combination with naltrexone treatment in opioid dependent individuals. ) To evaluate the efficacy of Iofexidine in enhancing naltrexone treatment in opioid dependent individuals on measures of (a) protracted opioid withdrawal symptoms; (b) opiate abstinence, and (c) naltrexone treatment adherence. (3) To assess naltrexone treatment outcomes at 1- and 3-month follow-up after 12-week Iofexidine/placebo treatment. 4) To examine whether individual differences in perceived stress and frequency and magnitude of stressful life events predicts Iofexidine treatment response and vulnerability to opiate relapse. Findings from this study will provide important information on whether pharmacologically targeting stress enhances naltrexone treatment, and whether the combination provides an efficacious opiate relapse prevention intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA018219-02
Application #
6952239
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Montoya, Ivan
Project Start
2004-09-23
Project End
2008-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
2
Fiscal Year
2005
Total Cost
$370,440
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Hyman, Scott M; Hong, Kwang-Ik A; Chaplin, Tara M et al. (2009) A stress-coping profile of opioid dependent individuals entering naltrexone treatment: a comparison with healthy controls. Psychol Addict Behav 23:613-9
Sinha, Rajita (2008) Chronic stress, drug use, and vulnerability to addiction. Ann N Y Acad Sci 1141:105-30
Sinha, Rajita (2007) The role of stress in addiction relapse. Curr Psychiatry Rep 9:388-95
Hyman, Scott M; Fox, Helen; Hong, Kwang-Ik A et al. (2007) Stress and drug-cue-induced craving in opioid-dependent individuals in naltrexone treatment. Exp Clin Psychopharmacol 15:134-43
Sinha, Rajita; Kimmerling, Anne; Doebrick, Cheryl et al. (2007) Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings. Psychopharmacology (Berl) 190:569-74