NCT03418623

Effect of GET73 on MRS Measures of Central Glutamate and GABA in Individuals With Alcohol Use Disorder

Effect of GET73 on Magnetic Resonance Spectroscopy Measures of Central Glutamate and GABA and Alcohol Cue-elicited Brain Activation in Recently Abstinent Non-treatment Seeking Individuals With Alcohol Use Disorder.

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Laboratorio Farmaceutico Ct S.r.l. · Industry
• Sex: All
• Age: 21 Years – 40 Years
• Healthy volunteers: Not accepted

Summary

This study is aimed at examining whether GET73 modulates the indices of central glutamate and γ-aminobutyric acid (GABA) levels in recently abstinent subjects that meet Alcohol Use Disorder (AUD) criteria, as measured by proton nuclear magnetic resonance spectroscopy (¹H-MRS), in order to provide a human translation of the findings demonstrated in different preclinical models, both in vitro and in vivo. In addition, the study will examine the effects of GET73 on alcohol cue induced brain activation by using a well-established blood-oxygen-level-dependent (BOLD) functional magnetic resonance (fMRI) paradigm in the same individuals. In summary, the study should provide important information on (i) the potential mechanism of action of GET73, (ii) on the brain mechanisms that would support its potential use for reduction in craving and drinking in AUD patients, and (iii) expand data on its safe use as a medication in heavy drinking individuals.

Detailed description

This study is aimed at examining whether GET73 modulates the indices of central glutamate and γ-aminobutyric acid (GABA) levels in recently abstinent subjects that meet Alcohol Use Disorder (AUD) criteria, as measured by proton nuclear magnetic resonance spectroscopy (¹H-MRS), in order to provide a human translation of the findings demonstrated in different preclinical models, both in vitro and in vivo. In addition, the study will examine the effects of GET73 on alcohol cue induced brain activation by using a well-established blood-oxygen-level-dependent (BOLD) functional magnetic resonance (fMRI) paradigm in the same individuals. In summary, the study should provide important information on (i) the potential mechanism of action of GET73, (ii) on the brain mechanisms that would support its potential use for reduction in craving and drinking in AUD patients, and (iii) expand data on its safe use as a medication in heavy drinking individuals. The enrolment period will last approximately 18 to 21 months. For each subject the study will last 25 to 45 days. The primary objective of the study is to evaluate whether GET73 modulates central glutamate levels in recently abstinent individuals with AUD, using proton nuclear magnetic resonance spectroscopy (¹H-MRS). The secondary objectives of the study are: 1. To evaluate whether GET73 modulates central GABA levels in recently abstinent individuals with AUD, using proton nuclear magnetic resonance spectroscopy (¹H-MRS) 2. To evaluate whether GET73 affects alcohol cue induced brain activity in reward areas of brain. 3. To explore whether the effects of GET73 on glutamate and GABA levels are related to its effects on alcohol cue induced brain activity. Safety Objective To evaluate the safety profile of GET73 in individuals with AUD, comparing Adverse Events (AEs) occurrence during GET73 treatment period vs placebo treatment period. This is a within-subject cross-over, randomized, double-blind, placebo-controlled study. Being a double blinded study, GET73 and placebo will be packaged identically. Both the Investigator and the study participant will be unaware of the treatment administered. The investigational product will be supplied to the Center packaged in "patient kits". Each "patient kit" will be made of 2 bottles (bottle A and bottle B) each containing 20 capsules of either GET73 or placebo. Being a cross-over design, all participants will receive both placebo and active treatment. The sequential order in which they will be administered to each participant will be defined by the randomization list. The participant will always receive bottle A in the phase A of the study and bottle B in phase B, but the content of the two bottles varies according to the randomization list. Research personnel will be blind to the content of the bottles, i.e. what study medication the subject is taking.

Conditions

• Alcohol Use Disorder

Interventions

Type	Name	Description
DRUG	GET73	GET73 300 mg oral capsules, administered three times a day on Visit 2 and 4, and twice a day on Visit 3 and 5.
OTHER	Placebo	Placebo oral capsules, administered three times a day on Visit 2 and 4, and twice a day on Visit 3 and 5.

Timeline

• Start date: 2018-03-08
• Primary completion: 2020-03-13
• Completion: 2020-03-13
• First posted: 2018-02-01
• Last updated: 2020-10-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study