Allopregnanolone for Alcoholism

Overseen By Ismene L Petrakis, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Alcoholism meds, Sedatives, Antibiotics, Antifungals

Disqualifiers: Psychiatric illnesses, Liver disease, Heart disease, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether allopregnanolone (also known as Brexanolone or Zulresso) can reduce cravings and anxiety triggered by stress, particularly in heavy drinkers. The study will test the effects of allopregnanolone through an infusion and compare it to a placebo, which contains no active drug. Ideal participants are those with an alcohol use disorder who are not currently seeking treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

You may need to stop taking certain medications to join this trial. Specifically, you cannot be on medications for alcoholism, sedating psychotropic medications, or antibiotics/antifungals.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that allopregnanolone, similar to the drug brexanolone, has undergone safety testing. The FDA has approved brexanolone for treating postpartum depression. In studies, some participants experienced side effects such as drowsiness, dry mouth, or fainting. However, these side effects were uncommon. Thus, while some risks exist, many individuals tolerate the treatment well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for stress-induced cravings focus on behavioral therapy or medications that alter neurotransmitter activity, like SSRIs. But allopregnanolone works differently, targeting the brain's response to stress by acting on GABA receptors, which are crucial for calming neural activity. Researchers are excited about allopregnanolone because it’s a naturally occurring neurosteroid that may offer a more direct way to reduce cravings triggered by stress, potentially leading to faster and more effective relief compared to current options. Additionally, the infusion delivery method allows precise control over dosing, which could enhance its effectiveness and reduce side effects.

What evidence suggests that allopregnanolone might be an effective treatment for stress-induced craving and anxiety?

Research has shown that allopregnanolone, a compound similar to brexanolone, might help reduce cravings and anxiety caused by stress. Allopregnanolone influences certain parts of the brain that control mood. In this trial, participants will receive either an allopregnanolone infusion or a placebo. Brexanolone, a similar drug, successfully treated postpartum depression by greatly reducing symptoms. In clinical trials, brexanolone outperformed a placebo, suggesting that allopregnanolone might also be effective. These findings offer hope that allopregnanolone could help manage stress-related cravings and anxiety. ^{5 6 7 8 9}

Who Is on the Research Team?

Elizabeth Ralevski, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

Inclusion Criteria

No current medical problems and normal ECG

For women, not pregnant as determined by pregnancy screening, not breast feeding

You cannot have an addiction to any drugs except for tobacco, alcohol, and marijuana.

Exclusion Criteria

weight >120kg

renal impairment

History of major medical illnesses; including liver diseases, heart disease, chronic pain or other medical conditions that the physician investigator deems contraindicated for the subject to be in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a continuous infusion of allopregnanolone or placebo for 175 minutes, followed by stress induction paradigm

1 day

1 visit (in-person)

Follow-up

Participants are monitored for stress-induced craving and anxiety, as well as mood effects, cognitive performance, and motor coordination

1 day

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Allopregnanolone

How Is the Trial Designed?

Group I: allopregnanolone Active Control 1 Intervention

Allopregnanolone infusion dose of 100nM over 175 min

Group II: placebo Placebo Group 1 Intervention

Placebo infusion

Allopregnanolone is already approved in United States for the following indications:

Approved in United States as Zulresso for:

• Postpartum depression

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8146562/

Brexanolone to Treat Postpartum Depression in Adult Women

In two double blind clinical trials, brexanolone was shown to reduce depressive symptoms, demonstrated by reduced Hamilton Depression Rating Scale (HAM-D) ...

2.

liebertpub.com

liebertpub.com/doi/10.1177/26884844251383702

Real-World Outcomes of Brexanolone to Treat Postpartum ...

FDA approved in August 2023, zuranolone demonstrated significant symptom improvement in two large, randomized trials, with effects observed as ...

3.

fda.gov

fda.gov/media/160147/download

NDA Multi-Disciplinary Review and Evaluation (ZULRESSO)

characteristics, and efficacy results for adult studies used to substantiate evidence of efficacy for Zulresso. Table 8 and Table 9 compares ...

4.

dig.pharmacy.uic.edu

dig.pharmacy.uic.edu/faqs/2024-2/april-2024-faqs/how-do-brexanolone-and-zuranolone-compare-in-patients-with-postpartum-depression/

How do brexanolone and zuranolone compare in patients with ...

Similarly, most patients in the brexanolone trials experienced an onset of PPD within 4 weeks postpartum (67% to 78%) and 17% to 26% of patients ...

5.

aetna.com

aetna.com/cpb/medical/data/900_999/0951.html

Brexanolone (Zulresso) - Medical Clinical Policy Bulletins

The authors found that, in both studies, titration to a target dose of brexanolone 90 mcg/kg/hour was superior to placebo in improvement of depressive symptoms.

6.

womensmentalhealth.org

womensmentalhealth.org/posts/post-marketing-safety-data-for-brexanolone-zulresso/

Post-Marketing Safety Data for Brexanolone (Zulresso)

Because preliminary studies indicated that brexanolone may have potentially serious side effects, including excessive sedation and sudden loss ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10491550/

Safety of Brexanolone in Adults with Postpartum Depression

Brexanolone is currently the only medication approved by the US FDA for the treatment of postpartum depression (PPD) in patients ≥15 years.

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf

Zulresso - accessdata.fda.gov

Based on findings from animal studies of other drugs that enhance GABAergic inhibition,. ZULRESSO may cause fetal harm. There are no available data on ZULRESSO ...

9.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37280463/

Safety of Brexanolone in Adults with Postpartum Depression

Results: Overall, 499 patients received brexanolone in this postmarketing surveillance analysis between June 2019 and December 2021 ( ...