GET73 for Alcoholism

Recruiting in Palo Alto (17 mi)

Overseen by James J Prisciandaro, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Medical University of South Carolina

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

Disqualifiers: Substance use disorder, Axis I disorders, others

Trial Summary

What is the purpose of this trial?

This trial tests a drug called GET73 on people who drink alcohol regularly but aren't looking for treatment. Participants will take the drug for a short period and have several study visits.

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.

What evidence supports the effectiveness of the drug GET73 for treating alcoholism?

Research suggests that GET73 may help treat alcohol use disorder by reducing alcohol-related brain damage and showing anti-alcohol effects in animal studies. It has also been found to be safe and well-tolerated in humans when taken with alcohol. ^{1 2 3 4 5}

Is GET73 safe for humans?

GET73 has been tested in healthy male volunteers and was found to be safe and well-tolerated, even at high doses, with only mild or moderate side effects reported. ^{1 3 4 6 7}

How does the drug GET73 differ from other treatments for alcoholism?

GET73 is a novel drug being explored for alcohol use disorder, offering a new potential option beyond the three widely-approved drugs (disulfiram, naltrexone, and acamprosate) and other repurposed medications. Its unique mechanism of action and potential for personalized treatment make it a promising candidate in the diverse landscape of alcohol use disorder therapies. ^{6 8 9 10 11}

Research Team

James J Prisciandaro, PhD

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• GET73 (CD73 inhibitor)
• Placebo (Other)

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.

Participant Groups

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+

Dr. Erik Summers

Medical University of South Carolina

Chief Medical Officer

MD from University of Alabama at Birmingham

Dr. Patrick J. Cawley

Medical University of South Carolina

Chief Executive Officer

MD, MBA

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Dr. Jeanne Marrazzo

National Institutes of Health (NIH)

Chief Medical Officer

MD from University of California, Los Angeles

Dr. Jay Bhattacharya

National Institutes of Health (NIH)

Chief Executive Officer

MD, PhD from Stanford University

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Dr. George F. Koob

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Chief Executive Officer since 2014

PhD in Neurobiology from the Scripps Research Institute

Dr. Patricia Powell

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Chief Medical Officer since 2015

MD from an accredited institution

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. [2023]

3. England pubmed.ncbi.nlm.nih.gov

GET73 Prevents Ethanol-Induced Neurotoxicity in Primary Cultures of Rat Hippocampal Neurons. [2016]

4. Germany 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. [2023]

5. United States 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. [2018]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. [2022]

7. Netherlands 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. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Drug adjuncts for treating alcohol dependence. [2019]

9. England 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. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Evaluation of alcohol use disorders pharmacotherapies in a new preclinical model of binge drinking. [2019]

11. Netherlands 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. [2017]