Trial of Ibudilast for Methamphetamine Dependence (IBUD ph II)

This study is currently recruiting participants.
Verified November 2013 by University of California, Los Angeles
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Keith Heinzerling, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01860807
First received: May 20, 2013
Last updated: November 8, 2013
Last verified: November 2013

May 20, 2013
November 8, 2013
July 2013
June 2017   (final data collection date for primary outcome measure)
Methamphetamine use [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01860807 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Trial of Ibudilast for Methamphetamine Dependence
Randomized Trial of Ibudilast for Methamphetamine Dependence

The objective of this study is to test the safety and potential efficacy of ibudilast to treat methamphetamine dependence. The study hypotheses are that ibudilast will reduce methamphetamine use and increase treatment retention more than placebo among patients seeking treatment for methamphetamine dependence. As HIV infection is a common complication of methamphetamine dependence, half of the participants will be HIV positive and the study will assess whether ibudilast also improves HIV related outcomes (e.g. medication adherence, CD4 count, risk behaviors).

Ibudilast (IBUD) is a macrophage migration inhibitory factor (MIF) and phosphodiesterase (PDE)-4 and -10 inhibitor at peak clinical exposures (Rolan, Hutchinson et al. 2009) that increases glial cell line-derived neurotrophic factor (GDNF) expression (Mizuno, Kurotani et al. 2004) and reduces microglial activation (Suzumura, Ito et al. 1999; Suzumura, Ito et al. 2003), including HIV-induced glial activation (Kiebala and Maggirwar 2011). IBUD significantly reduces methamphetamine (MA) prime- and stress-induced reinstatement of MA seeking in rats (Beardsley, Shelton et al. 2010) and has multiple effects that may make it an effective treatment for MA dependence including amelioration of dopaminergic and neuroinflammatory dysfunction. Multiple studies implicate glial cells in a variety of neurodegenerative diseases (Hirsch and Hunot 2009; Sidoryk-Wegrzynowicz, Wegrzynowicz et al. 2011) including MA dependence and HIV infection (Nath 2010). Activated glial cells secrete pro-inflammatory mediators (Minghetti, Ajmone-Cat et al. 2005) that may exacerbate MA-induced dopaminergic dysfunction. Glial cells also produce neurotrophic factors, including GDNF, which may ameliorate dopaminergic dysfunction (Pascual, Hidalgo-Figueroa et al. 2008). Thus, IBUD may be an effective medication for MA dependence due to its modulation of glial cell activation resulting in amelioration of dopaminergic and neurocognitive dysfunction and improved treatment outcomes in MA dependence. IBUD may also have unique effects in HIV positive MA users as it may additionally block the degradation of neuronal integrity seen in HIV infection (Chana, Everall et al. 2006; Dash, Gorantla et al. 2011).

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Methamphetamine Dependence
  • HIV Infection
  • Drug: Ibudilast
  • Drug: Placebo
  • Experimental: Ibudilast
    Ibudilast 50 mg twice daily
    Intervention: Drug: Ibudilast
  • Placebo Comparator: Placebo
    matching placebo twice daily
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
140
June 2017
June 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. 18 years of age or older;
  2. meet DSM-IV-TR criteria for MA dependence (SCID verified);
  3. a MA-positive urine drug screen at one or more visit during the two week lead-in period;
  4. seeking treatment for MA problems;
  5. willing and able to comply with study procedures;
  6. provide written informed consent;
  7. English speaking
  8. reside within 35 miles of the clinical research site; and
  9. if female of childbearing potential, not pregnant or lactating and willing to use a medically reliable method of birth control during the trial (e.g., birth control pills, Depo-Provera, and/or condoms with spermicide).

Exclusion Criteria:

  1. a medical condition that, in the study physician's judgment, may interfere with safe study participation (e.g., active TB; unstable cardiac, renal, or liver disease; uncontrolled hypertension; unstable diabetes);
  2. CD4 count < 50 cells/mm3 (suggestive of advanced HIV infection)
  3. AST, ALT, or GGT > 3 times upper normal limit;
  4. current ongoing treatment with psychotropic medications (e.g., antidepressants, antipsychotics, antiepileptics, sedative/hypnotics, narcotic analgesics);
  5. a neurological disorder (e.g., organic brain disease, dementia) or a medical condition which would make study agent compliance difficult or which would compromise informed consent;
  6. a major psychiatric disorder not due to substance abuse (e.g., schizophrenia, bipolar disorder) as assessed by the SCID;
  7. attempted suicide in the past 3 years and/or serious suicidal intention or plan in the past year as assessed by the C-SSRS;
  8. currently on prescription medication that is contraindicated for use with IBUD including alpha or beta agonists, theophylline, or other sympathomimetics;
  9. current dependence on cocaine, opiates, alcohol, or benzodiazepines as defined by DSM-IV-TR;
  10. alcohol dependence within the past year;
  11. greater than one urine specimens during the lead-in with a riboflavin concentration of < 900 ng/ml as assessed via UV fluorescence;
  12. a history of sensitivity to IBUD; or
  13. any other circumstances that, in the opinion of the investigators, would compromise participant safety.
Both
18 Years and older
No
Contact: Keith Heinzerling, MD 323-461-3106 kheinzerling@mednet.ucla.edu
United States
 
NCT01860807
1 R01 DA035054-01, R01DA035054
Yes
Keith Heinzerling, University of California, Los Angeles
University of California, Los Angeles
National Institute on Drug Abuse (NIDA)
Principal Investigator: Keith Heinzerling, MD University of California, Los Angeles
University of California, Los Angeles
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP