Safety Study to Assess Atomoxetine With MA Abusers and Healthy Controls

NCT02014064 | Completed Phase 1 DMC

• 1 other identifier: NCT02014064
• Study Type: interventional
• Target: 41
• Locations: 0 countries
• Sites: N/A

Brief Summary

Methamphetamine (MA) abuse is a national public health concern. People who are dependent on MA have problems with mental functions (e.g., learning, remembering, focusing attention, solving problems). Such problems can interfere with their treatment for MA abuse, and thereby may promote continued drug use. While the effects of MA have been studied in rodents and non-human primates, its effects on the human brain have not been well characterized. This is a study of nontreatment seeking individuals who use MA compared to individuals who do not use MA(control participants). 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, placebocontrolled,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 structuraland 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 atomoxotime 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.

Conditions

Continuous Methamphetamine Dependence; Methamphetamine Dependence in Remission

Keywords

Methamphetamine, Atomoxetine, Clinical Pharmacology

Outcome Measures

Primary Outcomes (1)

• Cardiovascular & Subjective Effects of Methamphetamine & Atomoxetine

  Participants will be followed for the duration of the study, an expected average of 4 weeks

  4 weeks

Secondary Outcomes (3)

• The effects of administration of atomoxetine on the preference of MA-using subjects for MA (0 and 15mg, IV) versus escalating doses of money, from $0.25 to $64 in a Multiple-Choice Procedure.

  4 weeks

• The effects of atomoxetine administration on cognitive function, as determined by measures of performance on cognitive tests, such as working memory tasks and reaction time tests

  4 weeks

• The effects of administration of atomoxetine on BOLD fMRI signals in the brain in MA users and normal controls.

  4 weeks

Study Arms (2)

Atomoxetine

EXPERIMENTAL

Double-blind, Placebo controlled, 2-phase study the safety \& efficacy of Atomoxetine

Drug: Atomoxetine

Placebo

PLACEBO COMPARATOR

Control Group Schedule: Day 1: 40mg @ 8:00am Day 2: 40mg @ 8:00am Day 3: 40mg @ 8:00am, 40mg @ 8:00pm Day 4: 40mg @ 8:00am, 40mg @ 8:00pm Day 5: 40mg @ 8:00am, 40mg @ 8:00pm Day 6: 40mg @ 8:00am = Testing day (fMRI scan \& cognitive testing session)

Other: Placebo

Interventions

Atomoxetine DRUG

MA Group: Dispense 1 cap @ 8 AM on Treatment day 9 and 10 (total daily dose 40mg or 0); 1 cap SID @ 8 AM and 4 PM on day 11,12, and 13 (total daily dose 80mg or 0); 1 cap @ 8 AM on day 14 (total daily dose, 40mg or 0). Control Group Schedule: * Day 1: 40mg @ 8:00am * Day 2: 40mg @ 8:00am * Day 3: 40mg @ 8:00am, 40mg @ 8:00pm * Day 4: 40mg @ 8:00am, 40mg @ 8:00pm * Day 5: 40mg @ 8:00am, 40mg @ 8:00pm * Day 6: 40mg @ 8:00am = Testing day (fMRI scan \& cognitive testing session)

Also known as: Strattera

Atomoxetine

Placebo OTHER

Control Group: Day 1: 40mg @ 8am Day 2: 40mg @ 8am Day 3: 40mg @ 8am, 40mg @ 8pm Day 4: 40 mg @ 8am, 40mg @ 8pm Day 5: 40mg @ 8am, 40 mg @ 8pm Day 6: 40 mg @ 8am = Testing day (fMRI scan \& cognitive testing session)

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• MA ABUSING PARTICIPANTS:
• In order to participate in the study, MA-using subjects must:
• Be fluently English-speaking volunteers who meet DSM-IV criteria for MA abuse or dependence.
• Be between 18 and 50 years of age.
• Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures.
• Have smoked or injected methamphetamine for more than two years.
• Produce a methamphetamine-positive urine prior to study entry.
• Have an ECG performed that demonstrates normal sinus rhythm, normal conduction, and no clinically significant arrhythmias.
• Agree to abstain from MA during the study, evidenced by a MA-negative urine each morning of the study.
• 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.
• oral contraceptives
• barrier (diaphragm or condom) with spermicide, or condom only
• intrauterine progesterone, or non-hormonal contraceptive system
• levonorgestrel implant
• medroxyprogesterone acetate contraceptive injection

You may not qualify if:

• MA ABUSING PARTICIPANTS:
• A current or past history of seizure disorder, including alcohol- or stimulant-related seizure, febrile seizure, or significant family history of idiopathic seizure disorder.
• 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).
• Meet DSM-IV criteria (by SCID) for drug dependence other than meth, with the exception of nicotine and/or marajuna dependence.
• Any previous medically serious adverse reaction to MA including loss of consciousness, chest pain, or epileptic seizure resulting in hospitalization.
• 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.
• Evidence of clinically significant heart disease, hypertension or significant medical illness.
• Have any history of hypersensitivity to atomoxetine, glaucoma, motor tics or with a family history or diagnosis of Tourette's syndrome.
• Have any preexisting severe gastrointestinal narrowing, small bowel inflammatory disease, intestinal adhesions, past history of peritonitis, or cystic fibrosis.
• Be pregnant or nursing.
• Have a significant family history of early cardiovascular morbidity or mortality.
• 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).
• Be actively using albuterol or other beta agonist medications, regardless of formal diagnosis of asthma.
• 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 %.
• 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.

Sponsors & Collaborators

• University of California, Los Angeles: lead

MeSH Terms

Interventions

Atomoxetine Hydrochloride

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Study Officials

• Edythe London, Ph.D.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 5, 2011
• First Posted: December 17, 2013
• Study Start: August 1, 2009
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: May 12, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share