Methamphetamine Dependence in Remission Clinical Trial
Official title:
A Study to Assess the Cardiovascular, Cognitive and Subjective Effects of Atomoxetine in Combination With Intravenous Methamphetamine
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.
As a preliminary step, the investigators will screen the experimental data for normality and
for potential associations between outcome variables with demographic variables at baseline.
In cases of strong deviations from normality, log or power transformations will be used as
appropriate. For the subjective effects questionnaires, the peak effect will be identified
for each subject and used as the dependent variable. The primary analytical technique will
be linear mixed effects regression. The general linear mixed model (GLMM) is equivalent to
repeated measures ANOVA when all subjects have complete data but automatically handles
missing observations, producing unbiased estimates as long as the values are missing at
random. This approach will allow use of the data from subjects who complete only part of the
protocol or who have invalid measurements on some tests, greatly enhancing our power.
The sample size is as large or greater than those in the previous human laboratory studies
assessing safety and initial efficacy of agonist-like pharmacotherapies for stimulant
dependence. For example, these previous studies used samples of 7 (Herin et al., 2010;
Stoops et al., 2008; Dackis et al., 2003), and 10 (Sofuoglu et al., 2009) subjects to obtain
significant reductions in subjective effects of d-amphetamine by atomoxetine and those of
cocaine by modafinil.
To be conservative, the investigators base power estimates on completers but will use
available data from all 30 subjects in GLMM analyses. This should substantially increase
power (power for GLMM and repeated measures ANOVA are equivalent except that ANOVA cannot
utilize incomplete data, while a GLMM can).
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT04405193 -
The Efficacy of N-acetylcysteine Versus Placebo for the Treatment of Metamphetamine Withdrawal Symptoms
|
Phase 2/Phase 3 |