Clinical trial NCT06746831: Methamphetamine Isomer Pharmacology in Humans
Official title: The Low-Down on Methamphetamine Isomers: Prevalence and Pharmacology in Humans
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Methamphetamine
Keywords: pharmacology
meth
isomers
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: U.S. Department of Justice
First posted: 2024-12-24
Enrollment: 17
Sex: ALL
Minimum age (years): 21
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind crossover study design.
Primary purpose: TREATMENT

Brief summary: This study is being done to understand the metabolism and impairment profile of methamphetamine (meth). Meth exists as two chemical structures that are mirror images of each other: R-meth and S-meth. S-meth is a strong central nervous system stimulant and used to treat attention deficit disorder (ADD). R-meth is not a strong central nervous system stimulant and is available over-the-counter in nasal decongestant sprays.17 healthy participants will be enrolled for 3 study visits and on study for up to 12 weeks.

Detailed description: Double-blind crossover study design. Healthy volunteers will attend three study drug administration visits, at least 7 days apart, in which methamphetamine isomer pharmacology will be assessed following intravenous administration of (1) S-(+)-methamphetamine, (2) R(-)-methamphetamine, or (3) a (1:1) racemic mixture of R-(-)- and S-(+)-methamphetamine. The order of these interventions will be counterbalanced across participants. Serial blood samples will be drawn during each dosing visit and compared with concurrent dried blood spots from a finger stick, oral fluid collections, and pooled urine specimens.

Primary Objective

* Characterize the pharmacokinetics of acute S-(+)-methamphetamine administration.
* Characterize the pharmacokinetics of acute R-(-)-methamphetamine administration.
* Characterize the pharmacokinetics of acute racemic (1:1) R-(-)- and S-(+)-methamphetamine administration.

Secondary Objectives

* Assess for evidence of stereo-selective metabolic pathways.
* Assess for evidence of subjective, cognitive, or physiological effects from acute R-(-)-methamphetamine administration.
* Assess for evidence of more than additive effects when administering racemic methamphetamine.

Correlative Objectives

* Compare biological methamphetamine and metabolite concentrations in surveyed biological matrices (i.e., plasma, whole blood, oral fluid, dried capillary blood spots, and urine) over time.
* Compare cognitive and subjective effects of acute S-(+)-methamphetamine, R-(-)-methamphetamine, and racemic methamphetamine administration.

Eligibility criteria: Inclusion Criteria:

* Good mental health as determined by self-reported responses to the Psychopathology Screener
* Absence of any major cardiac, neurologic, psychiatric, oncologic, endocrine, metabolic, renal, or hepatic disease as determined by self-reported responses to the Medical History Screener
* English-speaking (able to provide consent and complete questionnaires)
* Written Informed Consent

Exclusion Criteria:

* Any serious prior adverse response to sympathomimetic agents or amphetamine analogs
* History of or current substance use disorder as determined by self-reported responses to the Internalizing, Externalizing, and Substance Use Disorder Screener
* Pregnancy or lactation (pregnancy test, if needed)
* Use of medications that may impact cognition or metabolism (e.g., mood stabilizers, sedatives)
* Dependent on prohibited concomitant therapy that cannot be withheld for 48 hours prior to and during study visits.

Primary outcomes:
measure: Peak concentration (Cmax)
timeFrame: pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 hours
measure: Area under the concentration versus time curve (AUC)
timeFrame: pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, 48 hours
Secondary outcomes:
measure: Cognitive Effects: Divided Attention Task (DAT)
timeFrame: Visit 1 (baseline), Visit 2 (week 1), Visit 3 (week 2)
measure: Cognitive Effects: Digital Symbol Substitution Task (DSST)
timeFrame: Visit 1 (baseline), Visit 2 (week 1), Visit 3 (week 2)
measure: Cognitive Effects: Paced Serial Addition Task (PASAT)
timeFrame: Visit 1 (baseline), Visit 2 (week 1), Visit 3 (week 2)
measure: Subjective Effects: Drug Effect Questionnaire (DEQ)
timeFrame: Visit 1 (baseline), Visit 2 (week 1), Visit 3 (week 2)
measure: Subjective Effects: Number of Participants Who Answer 'True' for Amphetamine-specific questions
timeFrame: Visit 1 (baseline), Visit 2 (week 1), Visit 3 (week 2)
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Heather K Barkholtz, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: David Leinweber, MD
role: PRINCIPAL_INVESTIGATOR
References: