Alcohol Use DisorderPhase 2NCT03418623
Effect of GET73 on MRS Measures of Central Glutamate and GABA in Individuals With Alcohol Use Disorder
A Phase 2 study testing GET73 in people with Alcohol Use Disorder, run by Laboratorio Farmaceutico Ct S.r.l. at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 to 40 years
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- GET73
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Mar 2018to 13 Mar 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male participants, or females who are post-menopausal or surgically sterile.
- Age between 21 and 40 years old (inclusive).
- Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current Alcohol Use Disorder, moderate severity (4 or more criteria met) as indicated by the Structured Clinical Interview for DSM-5 (SCID-5-RV).
- Reports drinking, on average, > 20 standard drinks per week in the 90 days prior to screening evaluation, and in the last week prior to screening.
- Must report drinking within the 48 hours prior to the first dose of medication in each study medication period.
- Positive for Ethyl Glucuronide (EtG) in urine (> 100 ng/ml) at screening and prior to the first dose of medication in each study medication period.
- Currently not engaged in, and does not want treatment for, alcohol related problems.
- Able to read and understand questionnaires and informed consent.
Who cannot join
- Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder.
- Any psychoactive substance use (except marijuana and nicotine) within the last 30 days before the screening visit, as indicated by self-report and/or urine drug screen.
- No marijuana use within the last seven days before the screening visit, by verbal report and negative urine drug test (< 50 ng/mL); if positive at screening, must be negative or decreasing urine Delta9-Tetrahydrocannabinol (THC) levels (corrected for urine creatinine level) at the second test (Day1 A-1).
- Current DSM-5 Axis I diagnosis, including major depression, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, bipolar affective disorder, schizophrenia, dissociative disorders, eating disorders, or any other psychotic or organic mental disorder.
- Current suicidal or homicidal ideation.
- Need for maintenance or acute treatment with any psychoactive medication, including antiepileptic medications.
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- Current use, or use in the past 30 days, of any medication known to affect alcohol intake (e.g., disulfiram, naltrexone, acamprosate, topiramate).
- History of severe alcohol withdrawal (e.g., seizure, delirium tremens), as evidenced by self-report or a Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) score > 10.
- Clinically significant medical problems (e.g., unstable hypertension, neurological, cardiovascular, renal, gastrointestinal, or endocrine problems) that would impair participation or limit medication ingestion.
- Current or past hepatocellular disease, as indicated by verbal report or elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 300% the upper limit of the normal range, or bilirubin > 150% the upper limit of the normal range.
- Lack of a stable living situation.
- Presence of ferrous metal in the body, as evidenced by metal screening and self-report.
- Severe claustrophobia or weight > 300 pounds that preclude placement in the MRI scanner.
- History of head injury with > 2 minutes of unconsciousness.
- Participation in any behavioral and/or pharmacological study within the past 30 days;
- Concomitant use of CYP2C19 substrates; use of CYP2C19 and CYP3A4 inhibitors or inducers in the 14 days before dosing.
Trial locations and contacts
1 site in 1 country.
United States1 site
Department of Psychiatry and Behavioral Sciences - Medical University of South Carolina
Charleston, South Carolina, 29425
About this study
Official title: 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.
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.
Read the 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:
- To evaluate whether GET73 modulates central GABA levels in recently abstinent individuals with AUD, using proton nuclear magnetic resonance spectroscopy (¹H-MRS)
- To evaluate whether GET73 affects alcohol cue induced brain activity in reward areas of brain.
- 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
- Being tested
- GET73, Placebo
- Keywords
- Glutamate, Alcohol use, GABA, GET73, Non-treatment seeking
- Medical subject headings
- Alcoholism, Alcohol Drinking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GET73Drug
GET73 300 mg oral capsules, administered three times a day on Visit 2 and 4, and twice a day on Visit 3 and 5.
PlaceboOther
Placebo oral capsules, administered three times a day on Visit 2 and 4, and twice a day on Visit 3 and 5.
| Study group | Role | What they receive |
|---|---|---|
| GET73 | Experimental | GET73 is administered at the dose of 300 mg t.i.d. per day, with a minimum gap of 4 hours between administrations and a maximum gap of 9 hours. Each subject ingests a total of 5 capsules of GET73: 3 capsules of GET73 on the first day of the related phase, according to randomization, and 2 capsules on the second day of each phase. Receives: Drug: GET73 |
| Placebo | Placebo comparator | Placebo is administered t.i.d. per day, with a minimum gap of 4 hours between administrations and a maximum gap of 9 hours. Each subject ingests a total of 5 capsules of Placebo: 3 capsules of Placebo on the first day of the related phase, according to randomization, and 2 capsules on the second day. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentrations of glutamate in dorsal anterior cingulate measured via Proton Magnetic Resonance Spectroscopy
The presence of water and glutamate will be quantified through ¹H-MRS and the change in glutamate/water concentration between baseline and end of treatment will be assessed
Measured: After 5 doses of medication administered over 2 days, repeated after a wash-out period of 7 to 21 days (crossover design)
Secondary outcomes (2)
Concentrations of GABA in dorsal anterior cingulate measured via Proton Magnetic Resonance Spectroscopy
The presence of water and GABA will be quantified through ¹H-MRS and the change in GABA/water concentration between baseline and end of treatment will be assessed
Measured: After 5 doses of medication administered over 2 days, repeated after a wash-out period of 7 to 21 days (crossover design)
Change in the blood oxygenation level dependent (BOLD) signal to alcohol cues
Magnitude of change in the blood oxygenation level dependent (BOLD) signal to alcohol cues, relative to neutral beverage cues, in the ventral striatum and dorsal anterior cingulate cortex (alcohol cue reactivity task described in Schacht et al., 2013)
Measured: After 5 doses of medication administered over 2 days, repeated after a wash-out period of 7 to 21 days (crossover design)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2018
- Study start8 Mar 2018
- Primary completion13 Mar 2020
- Study completion13 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laboratorio Farmaceutico Ct S.r.l.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Latis S.r.l.
- Responsible party
- Sponsor
- Investigators
- Raymond F Anton, MD, Principal investigator, Department of Psychiatry and Behavioral Sciences - Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03418623
- Sponsor's protocol ID
- GET73 ¹H-MRS
- Status last verified
- Oct 2020
- First submitted
- 8 Jan 2018
- Last updated
- 8 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Schacht JP, Anton RF, Voronin KE, Randall PK, Li X, Henderson S, Myrick H. Interacting effects of naltrexone and OPRM1 and DAT1 variation on the neural response to alcohol cues. Neuropsychopharmacology. 2013 Feb;38(3):414-22. doi: 10.1038/npp.2012.195. Epub 2012 Oct 3.
PubMed 23032071
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT03418623
- Acronym / sponsor ID
- GET73 ¹H-MRS
- Conditions
- Alcohol Use Disorder
- Keywords
- Glutamate, Alcohol use, GABA, GET73, Non-treatment seeking
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Laboratorio Farmaceutico Ct S.r.l.Industry (pharma, biotech, devices)
- Collaborators
- Latis S.r.l.
- Study start
- 8 Mar 2018 (actual)
- Primary completion
- 13 Mar 2020 (actual)
- Study completion
- 13 Mar 2020 (actual)
- First posted
- 1 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To evaluate whether GET73 modulates central GABA levels in recently abstinent individuals with AUD, using proton nuclear magnetic resonance spectroscopy (¹H-MRS)
- To evaluate whether GET73 affects alcohol cue induced brain activity in reward areas of brain.
- 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| GET73 | Experimental | Drug: GET73GET73 is administered at the dose of 300 mg t.i.d. per day, with a minimum gap of 4 hours between administrations and a maximum gap of 9 hours. Each subject ingests a total of 5 capsules of GET73: 3 capsules of GET73 on the first day of the related phase, according to randomization, and 2 capsules on the second day of each phase. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo is administered t.i.d. per day, with a minimum gap of 4 hours between administrations and a maximum gap of 9 hours. Each subject ingests a total of 5 capsules of Placebo: 3 capsules of Placebo on the first day of the related phase, according to randomization, and 2 capsules on the second day. |
Who may qualify
- Ages
- 21 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Male participants, or females who are post-menopausal or surgically sterile.
- Age between 21 and 40 years old (inclusive).
- Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current Alcohol Use Disorder, moderate severity (4 or more criteria met) as indicated by the Structured Clinical Interview for DSM-5 (SCID-5-RV).
- Reports drinking, on average, > 20 standard drinks per week in the 90 days prior to screening evaluation, and in the last week prior to screening.
- Must report drinking within the 48 hours prior to the first dose of medication in each study medication period.
Key exclusion criteria (16 listed)
- Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder.
- Any psychoactive substance use (except marijuana and nicotine) within the last 30 days before the screening visit, as indicated by self-report and/or urine drug screen.
- No marijuana use within the last seven days before the screening visit, by verbal report and negative urine drug test (< 50 ng/mL); if positive at screening, must be negative or decreasing urine Delta9-Tetrahydrocannabinol (THC) levels (corrected for urine creatinine level) at the second test (Day1 A-1).
- Current DSM-5 Axis I diagnosis, including major depression, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, bipolar affective disorder, schizophrenia, dissociative disorders, eating disorders, or any other psychotic or organic mental disorder.
- Current suicidal or homicidal ideation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GET73GET73 300 mg oral capsules, administered three times a day on Visit 2 and 4, and twice a day on Visit 3 and 5. | Drug | GET73 |
| PlaceboPlacebo oral capsules, administered three times a day on Visit 2 and 4, and twice a day on Visit 3 and 5. | Other | Placebo |
Primary outcome
Concentrations of glutamate in dorsal anterior cingulate measured via Proton Magnetic Resonance Spectroscopy
Time frame: After 5 doses of medication administered over 2 days, repeated after a wash-out period of 7 to 21 days (crossover design)
The presence of water and glutamate will be quantified through ¹H-MRS and the change in glutamate/water concentration between baseline and end of treatment will be assessed
2 secondary outcomes
Concentrations of GABA in dorsal anterior cingulate measured via Proton Magnetic Resonance Spectroscopy
Time frame: After 5 doses of medication administered over 2 days, repeated after a wash-out period of 7 to 21 days (crossover design)
Change in the blood oxygenation level dependent (BOLD) signal to alcohol cues
Time frame: After 5 doses of medication administered over 2 days, repeated after a wash-out period of 7 to 21 days (crossover design)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
- Background: PubMed 23032071Schacht JP, Anton RF, Voronin KE, Randall PK, Li X, Henderson S, Myrick H. Interacting effects of naltrexone and OPRM1 and DAT1 variation on the neural response to alcohol cues. Neuropsychopharmacology. 2013 Feb;38(3):414-22. doi: 10.1038/npp.2012.195. Epub 2012 Oct 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raymond F Anton, MD principal investigator
Department of Psychiatry and Behavioral Sciences - Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GET73 in people with Alcohol Use Disorder, run by Laboratorio Farmaceutico Ct S.r.l. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentrations of glutamate in dorsal anterior cingulate measured via Proton Magnetic Resonance Spectroscopy (time frame: After 5 doses of medication administered over 2 days, repeated after a wash-out period of 7 to 21 days (crossover design)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03418623, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.