Topiramate for AUD and PTSD

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Charles Marmar, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: NYU Langone Health

Must not be taking: CNS depressants, Anticonvulsants, Metformin, others

Disqualifiers: Schizophrenia, Bipolar, Severe TBI, others

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a double-blind, 2-group randomized controlled trial evaluating the effects of topiramate versus placebo in patients with comorbid PTSD and moderate-to-severe AUD. This trial will provide one of the first rigorous tests of whether the effects of topiramate in AUD generalize to patients with co-occurring PTSD, and one of the first rigorous tests of whether topiramate has beneficial effects on PTSD symptoms in this population. It will be the first study to test whether the rs2832407 genotype predicts clinical response to topiramate for AUD and PTSD in patients with both disorders. Further, it will contribute to the understanding of topiramate's mechanisms of action in the co-morbid AUD/PTSD population, and to the discovery of predictors of treatment response.

Will I have to stop taking my current medications?

The trial requires stopping certain medications that could interact negatively, such as specific anticonvulsants, metformin, and treatments for addictions. Antidepressants are allowed if the dose is stable for at least 4 weeks before the trial and remains unchanged during the study. If you're on any of these medications, you may need to stop or adjust them before participating.

What data supports the effectiveness of the drug Topiramate for treating PTSD?

Research suggests that Topiramate may help treat PTSD by reducing symptoms like nightmares and re-experiencing traumatic events. Some studies have shown it to be effective and well-tolerated in both civilian and combat-related PTSD cases. ^{1 2 3 4 5}

Is topiramate safe for humans?

Topiramate, including its extended-release forms like Trokendi XR and Qudexy XR, has been studied for safety and tolerability in various conditions. Some studies have reported treatment-emergent adverse events (side effects that occur during treatment), but it is generally considered safe for use in humans when monitored by a healthcare provider. ^{1 3 4 6 7}

How is the drug topiramate unique for treating AUD and PTSD?

Topiramate is unique because it may help reduce symptoms of both alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) by affecting brain chemicals involved in these conditions. It is an anticonvulsant that works on both inhibitory and excitatory neurotransmitters, which might make it effective for PTSD, and it is being studied for its potential to reduce alcohol use in people with both disorders. ^{4 5 6 7 8}

Eligibility Criteria

Adults aged 18-70 with both PTSD and moderate-to-severe alcohol use disorder (AUD) who want to reduce or stop drinking can join. They must be willing to use contraception if applicable, have a stable living situation, and have had several heavy drinking days recently. Excluded are those with significant health issues like liver or kidney problems, certain severe mental health conditions, recent inpatient psychiatric treatment (except for detox), current severe substance abuse other than alcohol/nicotine, or on conflicting medications.

Inclusion Criteria

DSM-5 diagnosis of moderate or severe AUD (using SCID5)

You want to reduce or quit drinking alcohol.

You have consumed at least four or more alcoholic drinks per day (for women) or five or more alcoholic drinks per day (for men) on at least four days within the past 30 days.

Exclusion Criteria

Pregnancy or lactation

You are currently being treated for addiction to methadone or opioids.

You are allergic or have a bad reaction to topiramate.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive topiramate or placebo, titrated over 8 weeks to a maximum dose of 200 mg, continued for 4 more weeks, followed by a 2-week taper

14 weeks

Weekly visits for dose titration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo (Other)
• Topiramate (Anti-epileptic drug)

Trial Overview The trial is testing the effectiveness of topiramate compared to a placebo in treating people who suffer from both PTSD and AUD. It's double-blind meaning neither participants nor researchers know who gets the real drug versus placebo. The study also explores whether genetic factors influence how well topiramate works for these conditions.

Participant Groups

Group I: Topiramate Experimental Treatment 1 Intervention

Week 0-1: 25 mg qhs Week 1-2: 25 mg qAM, 25 mg qhs Week 2-3: 25 mg qAM, 50 mg qhs Week 3-4: 50 mg qAM, 50 mg qhs Week 4-5: 50 mg qAM, 75 mg qhs Week 5-6: 75 mg qAM, 75 mg qhs Week 6-7: 75 mg qAM, 100 mg qhs Week 7-8: 100 mg qAM, 100 mg qhs Week 8-10: 100 mg qAM, 100 mg qhs Week 10-12: 100 mg qAM, 100 mg qhs Week 12-14: 2-week taper

Group II: Placebo Placebo Group 1 Intervention

Placebo

Topiramate is already approved in United States, European Union, Canada, Japan, Australia for the following indications:

🇺🇸 Approved in United States as Topamax for:

• Epilepsy
• Migraine prophylaxis
• Alcohol use disorder (off-label)
• Post-traumatic stress disorder (off-label)

🇪🇺 Approved in European Union as Topamax for:

• Epilepsy
• Migraine prophylaxis

🇨🇦 Approved in Canada as Topamax for:

• Epilepsy
• Migraine prophylaxis

🇯🇵 Approved in Japan as Topamax for:

• Epilepsy

🇦🇺 Approved in Australia as Topamax for:

• Epilepsy
• Migraine prophylaxis

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

NYULH New York, NY

New York University School of Medicine New York, NY

Who Is Running the Clinical Trial?

NYU Langone Health Lead Sponsor

National Institute on Alcohol Abuse and Alcoholism (NIAAA) Collaborator

References

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

Treatment of civilian and combat-related posttraumatic stress disorder with topiramate. [2018] To evaluate the use of topiramate for the treatment of posttraumatic stress disorder (PTSD).

2. Netherlands pubmed.ncbi.nlm.nih.gov

[Topiramate for the treatment of post traumatic stress disorder. A case study]. [2018] Two patients with posttraumatic stress disorder (PTSD) were treated successfully with the anti-epileptic drug topiramate. Nightmares and the re-experiencing of traumatic events were particularly responsive to the treatment. Topiramate acted rapidly at a relatively low dosage and seems to be an important addition to the limited range of drugs availablefor treating severe symptoms of PTSD.

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

A double-blind randomized controlled trial to study the efficacy of topiramate in a civilian sample of PTSD. [2021] To evaluate the efficacy and tolerability of topiramate in patients with posttraumatic stress disorder (PTSD).

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

Real-world assessment of treatment with extended-release topiramate (Trokendi XR®) and comparison with previous immediate-release topiramate treatment. [2019] Label="AIM">Examine clinical profile of extended-release topiramate (Trokendi XR®) and compare treatment-emergent adverse events (TEAEs) associated with Trokendi XR versus previous immediate-release topiramate (TPM-IR) treatment.

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

A randomized, double-blind, placebo-controlled trial to assess the efficacy of topiramate in the treatment of post-traumatic stress disorder. [2023] Topiramate might be effective in the treatment of posttraumatic stress disorder (PTSD) because of its antikindling effect and its action in both inhibitory and excitatory neurotransmitters. Open-label studies and few controlled trials have suggested that this anticonvulsant may have therapeutic potential in PTSD. This 12-week randomized, double-blind, placebo-controlled clinical trial will compare the efficacy of topiramate with placebo and study the tolerability of topiramate in the treatment of PTSD.

6. England pubmed.ncbi.nlm.nih.gov

Topiramate treatment of alcohol use disorder in veterans with posttraumatic stress disorder: a randomized controlled pilot trial. [2021] The course of posttraumatic stress disorder (PTSD) is frequently and severely complicated by co-occurring alcohol use disorder (AUD), yet there are few reports of pharmacologic treatments for these comorbid conditions. The objective of this pilot study was to obtain a preliminary assessment of the efficacy and safety of topiramate in reducing alcohol use and PTSD symptoms in veterans with both disorders.

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

USL255 extended-release topiramate: dose-proportional pharmacokinetics and tolerability in healthy volunteers. [2021] Evaluate the pharmacokinetics (PK), safety, and tolerability of single doses of once-daily USL255, Qudexy XR (topiramate) extended-release capsules, over a wide dosing range.

8. Germany pubmed.ncbi.nlm.nih.gov

Therapeutic drug monitoring of topiramate with a new HPLC method, SPE extraction and high sensitivity pre-column fluorescent derivatization. [2019] Topiramate is a 2nd generation antiepileptic drug (AED) recently approved by the FDA for migraine prophylaxis. Its pharmacological activity already appears significant at low doses. Unfortunately, the difficulty in determining the drug in serum at low concentrations hampers the completion of accurate pharmacokinetic studies in humans. Only chromatographic methods allow reaching the necessary sensitivities.