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

Trial Summary

What is the purpose of this trial?

The overall objective of the proposed study is to determine if Dexmedetomidine HCl (BXCL501) is safe for treatment of alcohol use disorder (AUD) with comorbid posttraumatic stress disorder (PTSD) in an outpatient setting and also shows potential signals of efficacy thereby supporting the conduct of later phase clinical trials.

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.

What data supports the effectiveness of the drug Dexmedetomidine HCl (BXCL501) for treating Alcohol Use Disorder with PTSD?

Research suggests that dexmedetomidine, a drug with calming and pain-relieving effects, may help reduce anxiety and cognitive issues in PTSD, as seen in animal studies. Additionally, it has shown promise in preventing agitation in PTSD patients after surgery, indicating potential benefits for stress-related conditions. ^{1 2 3 4 5}

Is sublingual dexmedetomidine safe for humans?

Sublingual dexmedetomidine has been shown to be safe in humans, particularly for treating acute agitation in adults with schizophrenia or bipolar disorder, with mild somnolence (drowsiness) being the most common side effect. ^{1 6 7 8 9}

What makes sublingual dexmedetomidine unique for treating alcohol use disorder with PTSD?

Sublingual dexmedetomidine is unique because it is administered under the tongue, allowing for fast-acting sedation and anxiety relief without affecting breathing, which is different from many other treatments for alcohol use disorder and PTSD. It also has potential anti-inflammatory and neuroprotective effects, making it a novel option for managing stress-related symptoms in these conditions. ^{1 7 9 10 11}

Research Team

Ismene Petrakis, MD

Principal Investigator

VA Connecticut Healthcare System

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Dexmedetomidine in Psychiatry: Repurposing of its Fast-Acting Anxiolytic, Analgesic and Sleep Modulating Properties. [2023]

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

Emergence Delirium With Post-traumatic Stress Disorder Among Military Veterans. [2020]

3. Ireland 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Dexmedetomidine alleviates anxiety-like behaviors and cognitive impairments in a rat model of post-traumatic stress disorder. [2019]

5. England pubmed.ncbi.nlm.nih.gov

A pilot trial of prazosin, an alpha-1 adrenergic antagonist, for comorbid alcohol dependence and posttraumatic stress disorder. [2018]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Sublingual Dexmedetomidine for the Treatment of Agitation in Patients with Schizophrenia and Bipolar Disorder. [2023]

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

What Is the Role of Dexmedetomidine in Modern Anesthesia and Critical Care? [2023]

8. United States 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. [2022]

9. United States 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. [2023]

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

Evaluating the use of dexmedetomidine in neurocritical care patients. [2018]

11. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The use of dexmedetomidine in anesthesia and intensive care: a review. [2019]