GET73 for Alcoholism

Overseen By Sara Hix

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Medical University of South Carolina

Must not be taking: Psychoactive, Antiepileptic, Alcohol-affecting, CYP inhibitors

Disqualifiers: Substance use disorder, Axis I disorders, others

Compensation: Varies

Number of Visits: 4

Duration: 1 week

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of a new medication, GET73, on individuals who regularly consume alcohol and seek to understand its potential benefits for managing alcohol use. Participants will receive either the medication or a placebo (a dummy pill) for eight days, with four study visits and two MRI scans to monitor results. The trial seeks individuals who have consumed at least 20 alcoholic drinks per week for the past three months and are not currently seeking treatment for alcohol issues. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new medication.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop taking certain medications. The trial excludes those using CYP2C19 and/or CYP3A4 inhibitors or inducers, psychoactive medications, and medications affecting alcohol intake. Please consult with the trial team for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that GET73 may help reduce alcohol consumption and anxiety-related behaviors in animal studies. These studies have not identified major issues such as drowsiness or feeling unwell, suggesting the treatment is well-tolerated in animals. No direct information yet exists on how humans respond to GET73. The current trial is in its early stages, with researchers still gathering initial safety and tolerance data in humans. While GET73 shows potential, more information is needed to fully understand its safety in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

GET73 is unique because it focuses on a new mechanism of action to treat alcoholism. Unlike standard treatments like naltrexone or acamprosate, which mainly work by blocking cravings or restoring chemical balance, GET73 targets GABA-B receptors in the brain to potentially reduce alcohol consumption and cravings. Researchers are excited about this treatment because it could offer a new way to manage alcoholism, especially for those who haven't responded well to existing therapies. This fresh approach might provide more effective results, offering hope for better outcomes in managing alcohol dependence.

What evidence suggests that GET73 might be an effective treatment for alcoholism?

Research has shown that GET73, which participants in this trial may receive, may help reduce alcohol intake based on early studies. This new compound resembles gamma-hydroxybutyric acid (GHB), already used to treat alcohol problems. Early studies found that GET73 decreases alcohol consumption and has calming effects. It might also protect the brain from alcohol's harmful effects. These initial findings suggest that GET73 could be a promising treatment for alcohol use disorders. ^{2 3 5 6 7}

Who Is on the Research Team?

James J Prisciandaro, PhD

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for individuals aged 21-40 with a current Alcohol Use Disorder of at least moderate severity, who drink on average at least 20 alcoholic drinks per week. They must live within 50 miles of the study site and be able to abstain from alcohol before appointments. Exclusions include use of certain drugs, major psychiatric disorders, significant medical issues, pregnancy or not using birth control, pending violent crime charges, metal in body preventing MRI scans, severe claustrophobia or obesity.

Inclusion Criteria

I am willing to drink alcohol mixed with fruit juice.

You have been consistently drinking at least 20 standard alcoholic drinks per week for the past 3 months.

Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current Alcohol Use Disorder, with at least Moderate severity

Exclusion Criteria

Presence of ferrous metal in the body, as evidenced by metal screening and self-report

Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder

I am on medication that influences how much alcohol I drink.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive GET73 or placebo for an 8-day study

1 week

4 visits (in-person), including 2 MRI scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GET73
• Placebo

Trial Overview The study tests GET73's effects on regular alcohol drinkers who aren't seeking treatment. Participants will take either GET73 or a placebo over an eight-day period and attend four study visits that include two MRI scans to observe any changes in brain activity related to alcohol consumption.

How Is the Trial Designed?

Group I: Group B Experimental Treatment 1 Intervention

Group II: Group A Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

The FDA has approved three main drugs for treating alcoholism: disulfiram, naltrexone, and acamprosate, which are specifically designed to help individuals with alcohol dependence.

There is ongoing research into other medications, such as nalmafene, topiramate, and ondansetron, which are being used off-label, indicating a potential for new treatment options as our understanding of alcoholism improves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug adjuncts for treating alcohol dependence. Collins, GB., McAllister, MS., Adury, K.[2019]

In rat studies, the higher dose of GET 73 (100 mg/kg) reduced spontaneous locomotor activity when given with alcohol, but it did not affect alcohol-induced hypolocomotion or sedation, suggesting a potential mechanism for modulating alcohol effects.

In a human trial with 14 healthy volunteers, GET 73 was well tolerated at a dose of 300 mg, both with and without alcohol, indicating its safety and consistent pharmacokinetics regardless of alcohol consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of the metabotropic glutamate receptor subtype 5 allosteric modulator GET 73 with alcohol: A translational study in rats and humans. Haass-Koffler, CL., Goodyear, K., Loche, A., et al.[2020]

GET 73, a novel mGluR5 negative allosteric modulator, was found to be safe and well-tolerated in a Phase I study involving 80 healthy male volunteers, with no serious adverse events reported.

The study demonstrated a dose-related increase in plasma drug concentration, indicating that GET 73 is pharmacokinetically active and supports further investigation for treating neuropsychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I randomized clinical trial testing the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy volunteers. Haass-Koffler, CL., Goodyear, K., Long, VM., et al.[2018]

Alcoholism can be treated with currently approved medications like disulfiram, naltrexone, and acamprosate, which target different mechanisms related to alcohol's effects on the brain.

Future treatments may include new drugs like ondansetron, baclofen, and topiramate, as well as compounds targeting specific receptors involved in alcohol dependence, which could lead to more personalized and effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Heilig, M., Egli, M.[2023]

The Take Control computer-delivered behavioral platform for alcohol use disorder (AUD) trials showed similar placebo response rates compared to traditional therapist-delivered platforms, indicating it can effectively engage participants without increasing risk.

Participants using Take Control demonstrated higher medication adherence than those receiving therapist-delivered platforms, suggesting it may be a more efficient and cost-effective option for future AUD pharmacotherapy trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An exploratory evaluation of Take Control: A novel computer-delivered behavioral platform for placebo-controlled pharmacotherapy trials for alcohol use disorder. Devine, EG., Ryan, ML., Falk, DE., et al.[2018]

GET73 demonstrated neuroprotective effects against ethanol-induced neurotoxicity in rat hippocampal neurons, as it prevented reductions in cell viability and alterations in cell morphology caused by chronic ethanol exposure.

The study suggests that GET73 could be a promising therapeutic agent for alcohol use disorders, showing multifaceted properties that warrant further development for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GET73 Prevents Ethanol-Induced Neurotoxicity in Primary Cultures of Rat Hippocampal Neurons. Tomasini, MC., Borelli, AC., Beggiato, S., et al.[2016]

The benzodiazepine partial inverse agonist RO19-4603 significantly reduced ethanol (EtOH) intake in alcohol-preferring rats, with effective doses as low as 0.009 mg/kg, demonstrating both immediate and prolonged effects on drinking behavior over two days.

The study suggests that RO19-4603 may offer a potential therapeutic approach for reducing alcohol consumption, as it selectively decreased EtOH intake without affecting saccharin or food intake, indicating a targeted effect on alcohol reinforcement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the benzodiazepine inverse agonist RO19-4603 alone and in combination with the benzodiazepine receptor antagonists flumazenil, ZK 93426 and CGS 8216, on ethanol intake in alcohol-preferring (P) rats. June, HL., Greene, TL., Murphy, JM., et al.[2017]

GET 73 is safe and well-tolerated when taken with alcohol, showing no serious adverse events in a study involving alcohol-dependent individuals.

While GET 73 did not reduce alcohol craving or consumption in the lab, it did enhance the sedative effects of alcohol, suggesting further research is needed to explore its potential benefits in longer-term outpatient settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An inpatient human laboratory study assessing the safety and tolerability, pharmacokinetics, and biobehavioral effect of GET 73 when co-administered with alcohol in individuals with alcohol use disorder. Haass-Koffler, CL., Perciballi, R., Magill, M., et al.[2023]

Intermittent access to alcohol significantly increases binge-like drinking behavior in rats, as shown in a study with 47 rats (24 male and 23 female) that compared different access schedules for alcohol self-administration.

The study found that rats with intermittent access to alcohol displayed more punishment-resistant drinking patterns, suggesting that this method could be valuable for creating preclinical models of Alcohol Use Disorders (AUD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent-access operant alcohol self-administration promotes binge-like drinking and drinking despite negative consequences in male and female heterogeneous stock rats. Gage, GA., Muench, MA., Jee, C., et al.[2023]

Alcohol use disorder (AUD) is common but often under-treated, with only three approved medications, highlighting the need for more diverse and effective treatment options.

The review discusses various pharmacotherapies, including both approved and novel agents, showing promise for improving treatment efficacy and supporting personalized medicine approaches for individuals with AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. Burnette, EM., Nieto, SJ., Grodin, EN., et al.[2022]

A new rat model of binge drinking was developed using an operant self-administration paradigm, which effectively mimics binge drinking behavior and allows for testing of pharmacotherapies.

All tested medications for alcohol use disorder, including (R)-Baclofen and Naltrexone, were effective in reducing binge drinking, with some showing specific effects on motivation and the ability to prevent relapse after abstinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of alcohol use disorders pharmacotherapies in a new preclinical model of binge drinking. González-Marín, MC., Lebourgeois, S., Jeanblanc, J., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5895880/

In Vitro Functional Characterization of GET73 as Possible ... In preclinical studies this compound has shown the ability to reduce alcohol intake along with anxiolytic-like properties (Loche et al., 2012; ...

2. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2012.00008/full

Frontiers | Anti-Alcohol and Anxiolytic Properties of a New ... GET73 is a newly synthesized compound structurally related to the clinically used, alcohol-substituting agent, gamma-hydroxybutyric acid (GHB).

3. academic.oup.com academic.oup.com/alcalc/article/51/2/128/2888196

GET73 Prevents Ethanol-Induced Neurotoxicity in Primary ... Aims. N-[(4-trifluoromethyl) benzyl] 4-methoxybutyramide (GET73) may be considered a promising therapeutic agent for the treatment of alcohol use disorders.

4. researchgate.net researchgate.net/publication/249996126_The_New_Compound_GET73_N-4-trifluoromethylbenzyl4-methoxybutyramide_Regulates_Hippocampal_Aminoacidergic_Transmission_Possibly_Via_an_Allosteric_Modulation_of_mGlu5_Receptor_Behavioural_Evidence_of_it

The New Compound GET73, N-[(4-trifluoromethyl)benzyl ... Furthermore, behavioural findings demonstrating how this new compound reduces alcohol intake, displays anxiolytic properties, and influences ...

5. link.springer.com link.springer.com/article/10.1007/s40265-021-01670-3

Novel Agents for the Pharmacological Treatment of Alcohol ... 2 GET73. N-[(4-Trifluoromethyl) benzyl] 4-methoxybutyramide (GET73) is a GHB analogue that has shown promising in vitro and in vivo ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3278888/

Anti-Alcohol and Anxiolytic Properties of a New Chemical ... GET73 has a multifaceted pharmacological profile, including the capacity to reduce alcohol drinking and anxiety-related behaviors in rats.

7. en.wikipedia.org en.wikipedia.org/wiki/GET-73

GET-73 GET 73 is an investigational new drug, developed by Laboratorio Farmaceutico CT SRL, that is being evaluated for treating alcohol use disorder (AUD).