Effect of GET73 on MRS Measures of Central Glutamate and GABA in Individuals With Alcohol Use Disorder
Condition: Alcohol Use Disorder
MeSH terms: Alcoholism; Alcohol Drinking
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): GET73; Placebo
Intervention type(s): Drug; Other
Intervention description(s): GET73 300 mg oral capsules, administered three times a day on Visit 2 and 4, and twice a day on Visit 3 and 5.; Placebo oral capsules, administered three times a day on Visit 2 and 4, and twice a day on Visit 3 and 5.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: After the eligibility of a subject has been determined in an initial screening period, the study will be conducted in 2 consecutive phases: in the first phase (phase A) the participant will be administered GET73 or placebo in a randomized order, in the other phase (phase B), the participant will be administered the treatment not received during phase A.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Glutamate; Alcohol use; GABA; GET73; Non-treatment seeking