Official Title: “A Study to Assess the Cardiovascular, Cognitive and Subjective Effects of Atomoxetine in Combination With Intravenous Methamphetamine”

This is a study of 30 nontreatment seeking individuals who use MA compared to 30 individuals who do not use MA (control subjects). The study has three goals: 1. it aims to identify the brain regions and pathways that may contribute to the problems of MA abusers in performing mental tasks; 2. it will serve as a double-blind, placebo-controlled, within-subjects study to determine the safety and tolerability, and positive effects of MA in MA- abusing volunteers treated with atomoxetine or placebo; 3. It aims to compare the brain activity as measured by structural and functional magnetic resonance imaging (fMRI). These are noninvasive brain imaging procedures, that will be used to study brain function while control and MA using participants take atomoxetine or placebo and perform tests of memory and concentration.

MA abusing participants will undergo a 1-day outpatient screening and if it is safe for the participants to proceed with the study they will participate in two inpatient phases of the study that will occur in the UCLA research setting, the General Clinical Research Center.

The first inpatient stay will be 15 days, and the second will be a 9 days stay that includes drug administration and assessments. There will be at least a two week interval between inpatient phases. During the inpatient phases participants will receive alternating study drugs; atomoxetine or placebo and four sessions of IV MA administration or placebo.

The study schedule for control participants will include a 1-day outpatient screening and two phases of outpatient administration of atomoxetine or placebo with a two week study drug free interval between the phases. Four to five of the outpatient study visits will involve cognitive tests and brain imaging studies.

In addition, current research has linked certain genes that are related to neurotransmitters with drug abuse and memory impairment (e.g., A1 allele for the D2 dopamine receptor and catechol-O-methyltransferase). Therefore blood samples will be obtained to test for these genes in order to relate the findings to brain function.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Crossover Assignment, Safety Study

Study Primary Completion Date: March 2010

Intervention(s) in this Clinical Trial

• Drug: Atomoxetine
  • Based on random assignment, atomoxetine tablets will be administered once daily at 40 mg/day on the first two study days, then twice daily for the third, fourth and fifth study days, and once daily on the sixth study day, then stop.
• Drug: Placebo
  • Based on random assignment, placebo tablets will be administered once daily at 40 mg/day on the first two study days, then twice daily for the third, fourth and fifth study days, and once daily on the sixth study day, then stop.

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: Arm 1
• Active Comparator: Arm 2

Primary Measures

• Cardiovascular parameters and adverse events
  • Time Frame: Daily with IV MA infusion and medication
    Safety Issue?: Yes

Secondary Measures

• Subjective effects will be assessed using visual-analogue scales.
  • Time Frame: Daily with MA IV infusion and medication
    Safety Issue?: No

FOR MA ABUSING SUBJECTS ONLY

Inclusion Criteria:

In order to participate in the study, MA-using subjects must:

• 1. Be fluently English-speaking volunteers who meet DSM-IV criteria for MA abuse or dependence.
• 2. Be between 18 and 50 years of age.
• 3. Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures.
• 4. Have smoked or injected methamphetamine for more than two years.
• 5. Produce a methamphetamine-positive urine prior to study entry.
• 6. Have vital signs as follows: resting pulse between 50 and 90 bpm, blood pressures between 105-150mm Hg systolic and 45-90mm Hg diastolic. Note that a blood pressure of 150/90 and pulse of 90 is too high for randomization but will allow participants to be enrolled if an acceptable range is demonstrated on a separate occasion.
• 7. Have an ECG performed that demonstrates normal sinus rhythm, normal conduction, and no clinically significant arrhythmias.
• 8. Agree to abstain from MA during the study, evidenced by a MA-negative urine each morning of the study.
• 9. If female, have a negative pregnancy test and agree to use one of the following methods of birth control, or be postmenopausal, have had a hysterectomy or have been sterilized.
• 1. oral contraceptives
• 2. barrier (diaphragm or condom) with spermicide, or condom only
• 3. intrauterine progesterone,or non-hormonal contraceptive system
• 4. levonorgestrel implant
• 5. medroxyprogesterone acetate contraceptive injection
• 6. complete abstinence from sexual intercourse
• NOTE: Recent intermittent alcohol or other illicit drug use without physical dependence is allowable (however a benzodiazepine-free urine should be produced to document absence of recent use).

Exclusion Criteria:

• 1. A current or past history of seizure disorder, including alcohol- or stimulant-related seizure, febrile seizure, or significant family history of idiopathic seizure disorder.
• 2. A history of head trauma that resulted in neurological sequelae (e.g., with loss of consciousness [LOC] > 15 minutes, or that required hospitalization. Also, individuals with 3 or more head injuries with LOC > 5 minutes will be excluded).
• 3. Do not meet DSM-IV criteria (by SCID) for drug dependence other than meth, with the exception of nicotine and/or marijuana dependence.
• 4. Any previous medically serious adverse reaction to MA including loss of consciousness, chest pain, or epileptic seizure resulting in hospitalization.
• 5. Meeting diagnostic criteria or receiving psychopharmacological treatment for the following Axis I disorders within the last 6 months: anorexia nervosa, bulimia, psychosis, bipolar I disorder, organic brain disease, dementia, major depression, schizoaffective disorder, or schizophrenia.
• 6. Evidence of clinically significant heart disease, hypertension or significant medical illness.
• 7. Have any history of hypersensitivity to atomoxetine, glaucoma, motor tics or with a family history or diagnosis of Tourette's syndrome.
• 8. Have any preexisting severe gastrointestinal narrowing, small bowel inflammatory disease, intestinal adhesions, past history of peritonitis, or cystic fibrosis.
• 9. Be pregnant or nursing.
• 10. Have a significant family history of early cardiovascular morbidity or mortality.
• 11. Have a diagnosis of adult asthma, including those with a history of acute asthma within the past two years, and those with current or recent (past 2 years) treatment with inhaled or oral beta-agonist or steroid therapy (due to potential serious adverse interactions with methamphetamine).
• 12. Be actively using albuterol or other beta agonist medications, regardless of formal diagnosis of asthma. (Inhalers are sometimes used by MA addicts to enhance MA delivery to the lungs.) If respiratory disease is excluded and the subject will consent to discontinue agonist use, s/he may be considered for inclusion.
• 13. For subjects suspect for asthma but without formal diagnosis, 1) have a history of coughing and/or wheezing, 2) have a history of asthma and/or asthma treatment two or more years before, 3) have a history of other respiratory illness, e.g., complications of pulmonary disease (exclude if on beta agonists), 4) use over-the-counter agonist or allergy medication for respiratory problems (e.g., Primatene Mist): a detailed history and physical exam, pulmonary consult, and pulmonary function tests should be performed prior to including or excluding from the study or 5) have an FEV1 <70 %.
• 14. Have any illness, condition, and/or use of medications that in the opinion of the site Principal Investigator and the admitting physician would preclude safe and/or successful completion of the study.
• 15. Have active syphilis that has not been treated or refuse treatment for syphilis.
• 16. Be undergoing HIV treatment with antiviral and non-antiviral therapy.
• 17. Have AIDS according to the current CDC criteria for AIDS - MMWR 1999;48 (#RR-13:29-31).
• 18. Have neurological disorders including Parkinson's disease.
• 19. Have evidence of significant liver or kidney dysfunction.
• 20. Have a history of urinary retention or bladder outlet obstruction.
• 21. Be UCLA students or staff.
• 22. Have evidence of active tuberculosis infection.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute on Drug Abuse (NIDA)

Overall Clinical Trial Officials and Contacts

Steven Shoptaw, PhD Principal Investigator University of California, Los Angeles  

Overall Contact: Todd Zorick, MD PhD 888-791-9988 tzorick@mednet.ucla.edu

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01019707

Study ID Number: P50-18185-PI-EDL-A

ClinicalTrials.gov Identifier: NCT01019707

Health Authority: United States: Food and Drug Administration