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Safety Interaction Trial Ibudilast and Methamphetamine

This study has been completed.
Sponsor:
Collaborators:
MediciNova
Information provided by (Responsible Party):
Steve Shoptaw, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01217970
First received: October 6, 2010
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

This study is designed to collect data to determine whether a medication, ibudilast, is safe for use as a potential treatment for methamphetamine-dependent people. For 18 years in Japan and South Korea, ibudilast has been used safely in humans as a treatment for asthma, pulmonary, and cardiovascular disease. It is not known whether ibudilast is safe to use in outpatient settings with people who have methamphetamine dependence. This would be the first study to collect this information. This study is important because individuals with methamphetamine dependence often relapse to meth use, even when in treatment; some number of individuals who participate in an outpatient study will relapse to methamphetamine while taking ibudilast. It is crucial to know whether there may be interactions between ibudilast and methamphetamine before planning an outpatient clinical trial.Ibudilast is an exciting medication candidate for treating methamphetamine dependence. When individuals become abstinent from methamphetamine during early recovery, the body starts an inflammatory process in neurons, especially glial cells. Glial cells are important in that they provide support to the nerve cells that are involved in thought, movement, and other human activities. By dampening inflammation in glial cells, ibudilast may preserve glial and other nerve cells during early abstinence, which in turn may help individuals feel better and think better during treatment.

The study specific aims are to determine whether ibudilast alters:

  1. blood pressure and heart rate responses to methamphetamine;
  2. the ratings of craving or other drug experiences from methamphetamine;
  3. the reward/reinforcing effects of methamphetamine; and
  4. the metabolism of methamphetamine.

Over an enrollment period of 24 months, 12 methamphetamine-dependent participants who are not looking for treatment will complete this study.


Condition Intervention Phase
Methamphetamine-dependence
Substance Abuse
Drug: Ibudilast
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Phase I Safety Interaction Trial of Ibudilast With Methamphetamine

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 35 days ] [ Designated as safety issue: Yes ]
  • Number of Participants with Clinically Significant Changes in Cardiovascular Parameters as a Measure of Safety and Tolerability [ Time Frame: 35 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of participants with adverse outcomes on (1) VAS, drug-effect scale, subjective effects, etc., and (2) pharmacokinetics of methamphetamine as measures of efficacy [ Time Frame: 35 days ] [ Designated as safety issue: Yes ]

Enrollment: 11
Study Start Date: January 2011
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ibudilast 20mg BID
Ibudilast 20mg oral BID 7 days
Drug: Ibudilast
Ibudilast oral 20mg BID for 7 days
Other Name: MN166, AV411
Active Comparator: Ibudilast 50mg BID
Ibudilast 50mg oral BID 7 days
Drug: Ibudilast
Ibudilast oral 50mg BID for 7 days
Other Name: MN166, AV411
Placebo Comparator: Placebo
Placebo oral BID 7 days (0mg ibudilast)
Drug: Ibudilast
Placebo oral BID 7 days
Other Name: Sugar pill

Detailed Description:

This study is designed to collect data to determine whether a medication, ibudilast, is safe for use as a potential treatment for methamphetamine-dependent people. For 18 years in Japan and South Korea, ibudilast has been used safely in humans as a treatment for asthma, pulmonary, and cardiovascular disease. It is not known whether ibudilast is safe to use in outpatient settings with people who have methamphetamine dependence. This would be the first study to collect this information. This study is important because individuals with methamphetamine dependence often relapse to meth use, even when in treatment; some number of individuals who participate in an outpatient study will relapse to methamphetamine while taking ibudilast. It is crucial to know whether there may be interactions between ibudilast and methamphetamine before planning an outpatient clinical trial.

The study will be conducted at the Harbor-UCLA hospital to ensure the medical safety of participants, especially if there are unexpected interactions between ibudilast and methamphetamine on cardiovascular function. Methamphetamine can cause substantial increases in heart rate and blood pressure that last for about 3 hours. This study will measure whether people who are meth-dependent (and not looking for treatment) show increases in their heart rate and blood pressures when given methamphetamine above what is expected by methamphetamine alone and when at the recommended doses of ibudilast.

Ibudilast is an exciting medication candidate for treating methamphetamine dependence. When individuals become abstinent from methamphetamine during early recovery, the body starts an inflammatory process in neurons, especially glial cells. Glial cells are important in that they provide support to the nerve cells that are involved in thought, movement, and other human activities. By dampening inflammation in glial cells, ibudilast may preserve glial and other nerve cells during early abstinence, which in turn may help individuals feel better and think better during treatment.

The study specific aims are to determine whether ibudilast alters:

  1. blood pressure and heart rate responses to methamphetamine;
  2. the ratings of craving or other drug experiences from methamphetamine;
  3. the reward/reinforcing effects of methamphetamine; and
  4. the metabolism of methamphetamine.

Over an enrollment period of 24 months, 12 methamphetamine-dependent participants who are not looking for treatment will complete this study. Each participant will complete assessments of safety/tolerability, perceived effects of methamphetamine, and an assessment where subjects make choices between different amounts of money and methamphetamine. Each patient will stay in the hospital for a total of 27 nights. The first two days consist of safety infusions to make sure methamphetamine is tolerable. Then, each subject will start study medication and take a 7-day course of three conditions: placebo, ibudilast 20mg BID, and ibudilast 50mg ibudilast. Low dose ibudilast always precedes high dose ibudilast. The order of placebo being first or last is random.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. NOT seeking treatment for methamphetamine problems;
  2. English-speaking;
  3. Age 18-55;
  4. Meet SCID criteria for MA dependence;
  5. Self-reported history of MA use via injection or smoking AND at least one MA positive urine drug screening during eligibility;
  6. Resting heart rate 50-100BPM; Systolic BP 105-150 mm Hg; Diastolic BP 45-90 mm Hg stabilized within 2 days of admission;
  7. Baseline EKG demonstrating normal sinus rhythm, normal conduction, no clinically significant arrhythmias;
  8. Use of acceptable barrier method of birth control;
  9. If female, not pregnant or lactating;
  10. Have medical history and physical examination demonstrating no additional clinically significant contraindications for study participation, in judgment of investigators.

Exclusion Criteria:

  1. Current dependence on cocaine, opioids, marijuana, or alcohol;
  2. Liver function tests GE 3x upper limit of normal, or kidney function tests GE 2x the upper limit of normal;
  3. Current or past history of seizure disorder;
  4. History of head trauma;
  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: NCT01217970

Locations
United States, California
Harbor-UCLA Medical Center GCRC
Torrance, California, United States, 90502
Sponsors and Collaborators
University of California, Los Angeles
MediciNova
Investigators
Principal Investigator: Steven Shoptaw, PhD University of California, Los Angeles
  More Information

No publications provided

Responsible Party: Steve Shoptaw, Professor, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT01217970     History of Changes
Other Study ID Numbers: ShoptawPI_ibudilast, R01DA029804
Study First Received: October 6, 2010
Last Updated: December 2, 2013
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:
methamphetamine
dependence
stimulant
amphetamine
los angeles
meth
speed
crank
abuse

Additional relevant MeSH terms:
Ibudilast
Methamphetamine
Adrenergic Agents
Adrenergic Uptake Inhibitors
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
Enzyme Inhibitors
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Respiratory System Agents
Sympathomimetics
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 25, 2014