Phase IIa Study of AV411, a Glial Activation Inhibitor, for Opioid Withdrawal
Condition: Opioid-Related Disorders
MeSH terms: Opioid-Related Disorders
Intervention: AV411; Placebo (PCB)
Intervention description: Low (20 mg), and high dose (40 mg) of AV411 will be administered orally twice a day (BID) for two consecutive weeks; Placebo drug will be administered orally twice a day (BID) for two consecutive weeks
Intervention MeSH terms: Ibudilast
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 21 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: opioid withdrawal, analgesia

Summary:

      Repeated use and/or abuse of opioid medications is generally associated with a characteristic
      withdrawal syndrome that develops after cessation of drug administration. The present study
      is designed to evaluate the effectiveness of AV411 to alter opioid-induced withdrawal
      symptoms.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults between the ages of 21 and 45

          -  Current dependence on heroin according to (Diagnostic and Statistical Manual) DSM-IV
             criteria

          -  Non-treatment seeking

        Exclusion Criteria:

          -  Female participants who are currently pregnant or breastfeeding. Lack of effective
             birth control 10 days before Study Day 1 (15 days prior to the first PET scan)

          -  Self-reported use of methadone, buprenorphine, or levo-alpha-acetylmethadol (LAAM) in
             the past 14 days

          -  Participants who have a positive history of neurological illness (including epilepsy)
             or those who have received anti-convulsant therapy during the past 5 years

          -  Liver disease requiring medication or medical treatment, and/or aspartate or alanine
             aminotransferase levels greater than 3 times the upper limit of normal

          -  Gastrointestinal or renal disease that would significantly impair absorption,
             metabolism or excretion of study drug, or require medication or medical treatment

          -  Neurological or psychiatric disorders including psychosis, bipolar disorder, organic
             brain disease, any seizure history or other disorders that require treatment or that
             could make study compliance difficult

          -  Positive tuberculosis (PPD) TB skin test along with a clinical history and chest X-ray
             indicative of active tuberculosis. (Individuals who have a positive PPD test and have
             a negative chest X-ray, are not symptomatic for tuberculosis, and do not require
             anti-tuberculosis therapy will be eligible to participate. Participants will be asked
             if they ever tested positive for tuberculosis. If so, they will not be given a PPD and
             a chest X-ray and clinical history will be used for evaluation purposes).

          -  Presence or positive history of severe medical illness or any cardiovascular disease
             or heart abnormality, such as low hemoglobin (Hb < 13 g/dL in males, Hb < 11 g/dL in
             females), or BP > 150/90.

          -  Requirement for any of the following medications (current or within the past 4 weeks):
             psychotropics (including sedative/hypnotics, antidepressants, neuroleptics),
             anticonvulsants, antihypertensives, antiarrhythmics, or antiretroviral medications,.
             Participants on any current psychoactive prescription medications will be excluded.

          -  Current dependence (by DSM-IV criteria) on methadone, LAAM, or buprenorphine

          -  Participants for whom detoxification is not "clinically recommended" such as those
             with a significant history of overdose following detoxification

          -  Participation in an investigational drug study within the past 3 months

          -  Hypersensitivity to any of the medications used in this study

          -  Participants who are positive for HIV or chronic active hepatitis

          -  Metal implants or paramagnetic objects contained within the body which may interfere
             with the MRI scan, as determined in consultation with a neuroradiologist and according
             to the guidelines set forth in the following reference book commonly used by
             neuroradiologists: "Guide to MR procedures and metallic objects" Shellock Frank G.,
             Lippincott Williams & Wilkins Healthcare, Philadelphia, 2001.

          -  Lifetime exposure to radiation in the workplace, or participation in nuclear medicine
             procedures, including research protocols, in the past year

          -  Positive Allen Test indicating lack of collateral blood flow to hand

          -  History of Reynaud's syndrome