Trial of Ibudilast for Methamphetamine Dependence (IBUD ph II)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 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: July 1, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Methamphetamine Dependence
HIV Infection
Drug: Ibudilast
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Trial of Ibudilast for Methamphetamine Dependence

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Methamphetamine use [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 140
Study Start Date: July 2013
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ibudilast
Ibudilast 50 mg twice daily
Drug: Ibudilast
Placebo Comparator: Placebo
matching placebo twice daily
Drug: Placebo

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. A corrected QT of > 450 msecs in men or > 460 msec in women on at least two ECGs during the baseline period, or clinical risk factors for Torsades de Pointes (e.g. (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or requiring ongoing treatment with concomitant medication(s) with established risk of Torsades de Pointes (e.g. Amiodarone, Arsenic trioxide, Astemizole, Bepridil, Chloroquine, Chlorpromazine, Cisapride, Citalopram, Clarithromycin, Disopyramide, Dofetilide, Domperidone, Droperidol, Erythromycin, Flecainide, Halofantrine, Haloperidol, Ibutilide, Levomethadyl, Mesoridazine, Methadone, Moxifloxacin, Pentamidine, Pimozide, Probucol, Procainamide, Quinidine, Sotalol, Sparfloxacin, Terfenadine, Thioridazine, Vandetanib);
  5. current ongoing treatment with psychotropic medications (e.g., antidepressants, antipsychotics, antiepileptics, sedative/hypnotics, narcotic analgesics);
  6. 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;
  7. a major psychiatric disorder not due to substance abuse (e.g., schizophrenia, bipolar disorder) as assessed by the SCID;
  8. attempted suicide in the past 3 years and/or serious suicidal intention or plan in the past year as assessed by the C-SSRS;
  9. currently on prescription medication that is contraindicated for use with IBUD including alpha or beta agonists, theophylline, or other sympathomimetics;
  10. current dependence on cocaine, opiates, alcohol, or benzodiazepines as defined by DSM-IV-TR;
  11. alcohol dependence within the past year;
  12. greater than one urine specimens during the lead-in with a riboflavin concentration of < 900 ng/ml as assessed via UV fluorescence;
  13. a history of sensitivity to IBUD; or
  14. any other circumstances that, in the opinion of the investigators, would compromise participant safety;
  15. (15) current participation in another clinical trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01860807

Contacts
Contact: Keith Heinzerling, MD 323-461-3106 kheinzerling@mednet.ucla.edu

Locations
United States, California
UCLA Vine Street Clinic Recruiting
Los Angeles, California, United States, 90038
Contact: Gacia Tachejian    323-461-3106    kheinzerling@mednet.ucla.edu   
Principal Investigator: Keith Heinzeling, MD         
Sponsors and Collaborators
University of California, Los Angeles
Investigators
Principal Investigator: Keith Heinzerling, MD University of California, Los Angeles
  More Information

No publications provided

Responsible Party: Keith Heinzerling, Associate Professor in Residence, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT01860807     History of Changes
Other Study ID Numbers: 1 R01 DA035054-01, R01DA035054
Study First Received: May 20, 2013
Last Updated: July 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, Los Angeles:
methamphetamine
ibudilast
HIV

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Methamphetamine
Ibudilast
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Dopamine Uptake Inhibitors
Bronchodilator Agents
Anti-Asthmatic Agents

ClinicalTrials.gov processed this record on July 31, 2014