Sublingual Dexmedetomidine for Alcohol Use Disorder with PTSD

Overseen By Jenelle Newcomb, BA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance

Must not be taking: Alcoholism medications, Sedatives, Antihypertensives, Alpha-2 agonists

Disqualifiers: Bipolar, Psychotic disorders, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Dexmedetomidine HCl (BXCL501) is safe and potentially effective for treating individuals with both alcohol use disorder and PTSD (post-traumatic stress disorder). The researchers aim to determine if this medication can help manage these conditions outside a hospital setting. Participants will take varying doses of the drug over a month to assess safety and initial effectiveness. Suitable candidates for this trial have experienced alcohol issues and a traumatic event causing PTSD, with recent heavy drinking episodes. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including those for alcoholism, some psychotropic medications that cause sedation, antihypertensive medications, and specific adrenergic agents. However, non-sedative antidepressants used to treat PTSD are allowed.

Is there any evidence suggesting that Dexmedetomidine HCl (BXCL501) is likely to be safe for humans?

Research has shown that Dexmedetomidine HCl (BXCL501) is safe for individuals, even when consumed with alcohol. Studies suggest it could effectively treat conditions like PTSD and alcohol use disorder. Other research indicates that Dexmedetomidine can help reduce stress-related behaviors, potentially benefiting those dealing with chronic stress.

As this trial is in its early stages, the primary goal is to ensure the treatment's safety and tolerability before progressing to larger studies. Researchers are assessing whether the drug causes any serious side effects in participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for alcohol use disorder with PTSD, which often involve counseling and medications like naltrexone or disulfiram, BXCL501 offers a novel approach. This treatment uses dexmedetomidine HCl, a medication that acts on the brain's alpha-2 adrenergic receptors, which could help to reduce stress and anxiety associated with PTSD. Additionally, BXCL501 is administered sublingually, meaning it dissolves under the tongue, providing a potentially quicker onset of action. Researchers are excited because this unique mechanism and delivery method might offer a more effective and rapid response for those struggling with these dual conditions.

What evidence suggests that Dexmedetomidine HCl might be an effective treatment for alcohol use disorder with PTSD?

Research shows that Dexmedetomidine HCl (BXCL501), the investigational treatment in this trial, may help treat alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). Studies have found that it can reduce stress-related behaviors, potentially benefiting people with these conditions. One study discovered that patients sedated with dexmedetomidine were less likely to develop PTSD. Importantly, this treatment is considered safe for those who might drink alcohol during treatment. These findings suggest that BXCL501 could effectively manage symptoms of both AUD and PTSD. ^{1 2 3 4 6}

Who Is on the Research Team?

Ismene Petrakis, MD

Principal Investigator

VA Connecticut Healthcare System

Are You a Good Fit for This Trial?

This trial is for individuals with alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD). Participants should be outpatients, meaning they aren't staying in a hospital. Specific eligibility details are not provided, but typically participants must meet certain health criteria to join.

Inclusion Criteria

Have no clinically significant contraindications, in the judgement of the PI/study physician, for study participation (based on self-reported medical history and brief physical examination)

I am between 21 and 65 years old.

Able to read and write in English and sign the informed consent

Exclusion Criteria

Score > 4 on Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) at screening

I do not have serious liver or kidney problems.

Current bipolar disorder or psychotic disorders as determined by MINI-5

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BXCL501 with dose escalation from 40µg to 80µg twice per day over 28 days

4 weeks

Clinic visits on days 1, 5 (+/- 2 days), and during weeks 1, 2, 3, and 4

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexmedetomidine HCl (BXCL501)

Trial Overview The study is testing the safety and early effectiveness of two doses of Dexmedetomidine HCl (BXCL501), taken under the tongue at 40µg and 80µg, for treating AUD with PTSD. The goal is to see if it's safe enough for larger trials.

How Is the Trial Designed?

Group I: BXCL501 Dose Range 40µg to 160µg Experimental Treatment 2 Interventions

Participants will receive 40µg on days 1-2. On days 3 and 4, participants will receive 40µg twice per day. On days 5 and 6 participants will receive 40µg in the morning and 80µg in the evening. On days 7-28 participants will receive 80µg in the morning and evening. Dose escalation will follow the above schedule based on tolerability assessed by clinician.

Who Is Running the Clinical Trial?

Pharmacotherapies for Alcohol and Substance Use Disorders Alliance

Lead Sponsor

Trials

9

Recruited

350+

VA Connecticut Healthcare System

Collaborator

Trials

86

Recruited

8,800+

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Congressionally Directed Medical Research Programs

Collaborator

Trials

59

Recruited

10,600+

BioXcel Therapeutics Inc

Industry Sponsor

Trials

20

Recruited

2,400+

RTI International

Collaborator

Trials

201

Recruited

942,000+

Published Research Related to This Trial

In a phase 3 trial with 90 participants suffering from severe PTSD, MDMA-assisted therapy (MDMA-AT) showed a significant reduction in hazardous alcohol use compared to placebo therapy, suggesting it may help improve alcohol use in these patients.

MDMA-AT did not increase the risk of illicit drug use, indicating that it could be a safe option for treating individuals with both PTSD and alcohol or substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of MDMA-assisted therapy on alcohol and substance use in a phase 3 trial for treatment of severe PTSD. Nicholas, CR., Wang, JB., Coker, A., et al.[2022]

In a phase 3 study involving 380 adults with schizophrenia or schizoaffective disorder, sublingual dexmedetomidine (180 μg and 120 μg) significantly reduced symptoms of acute agitation compared to placebo, as measured by the Positive and Negative Syndrome Scale-Excited Component (PEC) scores at 2 hours postdose.

The most common side effects of dexmedetomidine included somnolence, dizziness, and hypotension, indicating that while it is effective, monitoring for these adverse events is important during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial. Citrome, L., Preskorn, SH., Lauriello, J., et al.[2022]

Sublingual dexmedetomidine (Igalmi) is a safe and effective treatment for acute agitation in adults with schizophrenia or bipolar disorder, as demonstrated in two phase 3 trials involving different dose strengths (180 μg and 120 μg).

Both doses significantly improved agitation scores compared to placebo within two hours, with mild somnolence being the most common side effect, indicating a favorable safety profile without serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual Dexmedetomidine for the Treatment of Agitation in Patients with Schizophrenia and Bipolar Disorder. Smith, CM., Santalucia, M., Bunn, H., et al.[2023]

Sublingual dexmedetomidine has a favorable efficacy profile for treating agitation in adults with schizophrenia or bipolar disorder, with a number needed to treat of 3 for significant response at 2 hours post-dose in both conditions.

The treatment's safety profile is also acceptable, as the number needed to harm for adverse events is generally greater than 10, except for somnolence, which has a number needed to harm of 7, indicating that the benefits outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual Dexmedetomidine for Agitation Associated with Schizophrenia or Bipolar Disorder: A Post Hoc Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed. Citrome, L., Risinger, R., Rajachandran, L., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39152094/

Dexmedetomidine HCL (BXCL501) as a potential ... BXCL501 is safe for use in humans who may drink alcohol while undergoing treatment. BXCL501 may be explored as a potential treatment for PTSD and AUD.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06335407

Study Details | NCT06335407 | Effect of Sublingual ... The overall objective of the proposed study is to determine if Dexmedetomidine HCl (BXCL501) is safe for treatment of alcohol use disorder (AUD) with ...

3. ir.bioxceltherapeutics.com ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-announces-publication-frontiers

Press Release Dexmedetomidine demonstrated a significant reduction in stress-induced behaviors, suggesting potential applications of BXCL501 in chronic ...

4. europepmc.org europepmc.org/article/med/39152094

A phase 1b, placebo-controlled crossover laboratory study. Dexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo-controlled crossover laboratory study.

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2806183

Effect of Dexmedetomidine on Posttraumatic Stress ... In this randomized clinical trial, the patients with trauma who were sedated with dexmedetomidine were less likely to develop PTSD compared with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10276303/

Effect of Dexmedetomidine on Posttraumatic Stress Disorder ... In this randomized clinical trial, the patients with trauma who were sedated with dexmedetomidine were less likely to develop PTSD compared with ...