Safety Assessment of Atomoxetine With MA IV Administration
Condition: Methamphetamine Abuse; Methamphetamine Dependence
Intervention: Atomoxetine, then Placebo; Placebo, then Atomoxetine
Intervention description: As this is a within-subject, crossover design, all subjects complete both study medication assignments in a double-blind fashion. Based on random assignment to start on either atomoxetine or placebo, study drug will be administered once daily at 40 mg/day on the first 2 study days, then twice daily for the third, fourth and fifth study days, and once daily on the sixth study day.; As this is a within-subject, crossover design, all subjects complete both study medication assignments in a double-blind fashion. Based on random assignment to start on either atomoxetine or placebo, study drug will be administered once daily at 40 mg/day on the first 2 study days, then twice daily for the third, fourth and fifth study days, and once daily on the sixth study day.
Intervention MeSH terms: Atomoxetine Hydrochloride
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: crystal meth; methamphetamine; substance abuse

Summary:

      This is a study of 4 nontreatment seeking individuals who were MA-dependent and the safety
      and tolerability of atomoxetine. This double-blind, placebo-controlled, within-subjects study
      is to determine the safety and tolerability of atomoxetine.

      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 components of
      the study that will occur in the University of California Los Angeles (UCLA) General Clinical
      Research Center (GCRC). 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 components. During the inpatient components participants will
      receive alternating study drugs; atomoxetine or placebo and four sessions of IV MA
      administration or saline.
    

Eligibility criteria:

        Inclusion Criteria:

          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.