Topiramate for AUD and PTSD

Recruiting at 1 trial location

Overseen By Dayeon Cho

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

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

Disqualifiers: Schizophrenia, Bipolar, Severe TBI, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 14 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether topiramate can help individuals with both PTSD (Post-Traumatic Stress Disorder) and moderate-to-severe AUD (Alcohol Use Disorder). Researchers aim to determine if topiramate reduces drinking and improves PTSD symptoms compared to a placebo (a non-active treatment). They are also investigating whether certain genetic markers can predict who will benefit most from the treatment. Suitable participants are those dealing with both conditions and seeking to reduce or stop drinking. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to important findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that topiramate is generally well-tolerated for treating alcohol use disorder (AUD). One study found that topiramate significantly reduced alcohol consumption and cravings compared to a placebo, indicating its effectiveness for this condition.

Regarding safety, topiramate has been tested in various situations. The FDA has already approved it for other uses, suggesting reasonable safety. However, results for its use in post-traumatic stress disorder (PTSD) are mixed. Some studies show benefits, while others do not find it as effective.

Like any medication, topiramate can cause side effects. Common ones include tingling sensations, loss of appetite, and weight loss. Serious side effects are rare but possible. Always consult a healthcare provider about potential risks and benefits before joining any trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Topiramate is unique because it targets both alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD), conditions that often occur together. Most treatments for AUD focus on reducing alcohol cravings or consumption, while PTSD treatments typically involve psychotherapy and medications like SSRIs. Topiramate stands out by potentially addressing the neurochemical imbalances involved in both conditions simultaneously. Researchers are excited about its dual-action potential, offering a more comprehensive approach to treating individuals with these co-occurring disorders.

What evidence suggests that topiramate might be an effective treatment for AUD and PTSD?

This trial will compare Topiramate with a placebo. Research has shown that Topiramate can help treat alcohol use disorder (AUD). Several studies have found it reduces drinking frequency and cravings more effectively than a placebo. Specifically, one study found that taking up to 300 mg per day greatly improved drinking habits. However, its effectiveness for post-traumatic stress disorder (PTSD) remains uncertain. Results have been mixed, with some studies showing only moderate benefits. While Topiramate appears promising for AUD, more research is needed to understand its impact on PTSD symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Charles Marmar, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Topiramate

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.

How Is the Trial Designed?

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 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

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

In a pilot study analyzing patients aged 6 and older, Trokendi XR (extended-release topiramate) was primarily used for migraine prevention and showed a significantly lower incidence of treatment-emergent adverse events (TEAEs) compared to immediate-release topiramate (TPM-IR).

The most common TEAEs associated with topiramate included cognitive symptoms, paresthesia, gastrointestinal issues, and decreased appetite/weight loss, but Trokendi XR demonstrated better tolerability, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world assessment of treatment with extended-release topiramate (Trokendi XR®) and comparison with previous immediate-release topiramate treatment. O'Neal, W., Hur, EE., Liranso, T., et al.[2019]

A new solid-phase extraction (SPE) method for measuring topiramate in serum has been developed, showing high sensitivity (2 ng/mL) and precision, which is crucial for accurate pharmacokinetic studies.

The study found that serum levels of topiramate were significantly lower in patients taking enzyme-inducing antiepileptic drugs compared to those on non-enzyme-inducing medications, indicating that these drugs can affect topiramate's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic drug monitoring of topiramate with a new HPLC method, SPE extraction and high sensitivity pre-column fluorescent derivatization. Bolner, A., De Riva, V., Galloni, E., et al.[2019]

In a 12-week study involving 35 patients with PTSD, topiramate significantly improved symptoms, with 82.35% of participants showing positive changes, particularly in reexperiencing and avoidance/numbing symptoms.

Topiramate was well tolerated and resulted in a greater reduction in PTSD symptoms compared to placebo, indicating its potential as an effective treatment option for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind randomized controlled trial to study the efficacy of topiramate in a civilian sample of PTSD. Yeh, MS., Mari, JJ., Costa, MC., et al.[2021]

Topiramate, an anti-epileptic drug, was successfully used to treat two patients with posttraumatic stress disorder (PTSD), showing rapid effectiveness at low dosages.

The treatment specifically reduced nightmares and the re-experiencing of traumatic events, highlighting its potential as a valuable option for managing severe PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Topiramate for the treatment of post traumatic stress disorder. A case study]. Aalbersberg, CF., Mulder, JM.[2018]

Topiramate may serve as a potential alternative or adjunct treatment for patients with posttraumatic stress disorder (PTSD) who do not respond to standard therapies, based on a review of various studies including case reports and trials.

While some studies reported significant reductions in PTSD symptoms, particularly in combat-related cases, the overall evidence is limited and mixed, with some trials showing no significant differences in outcomes. Adverse effects were noted but generally not serious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of civilian and combat-related posttraumatic stress disorder with topiramate. Andrus, MR., Gilbert, E.[2018]

A 12-week randomized, double-blind, placebo-controlled trial involving 72 adults with PTSD is investigating the efficacy and tolerability of topiramate, an anticonvulsant that may help due to its effects on neurotransmitters.

Previous studies suggest that topiramate could be a promising alternative treatment for PTSD, especially for patients who do not respond well to standard SSRIs, although more research is needed to confirm its effectiveness.

NCBI (Pubmed)

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. Mello, MF., Yeh, MS., Barbosa Neto, J., et al.[2023]

USL255, a once-daily extended-release formulation of topiramate, demonstrated a consistent pharmacokinetic profile with predictable plasma concentrations across a wide dosing range (25-1,400 mg) in healthy adults, indicating its potential effectiveness for treating epilepsy.

The maximum tolerated dose (MTD) for USL255 was established at 1,200 mg, and the drug was generally safe and well tolerated, suggesting it could be a viable treatment option for patients with epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

USL255 extended-release topiramate: dose-proportional pharmacokinetics and tolerability in healthy volunteers. Clark, AM., Halvorsen, MB., Braun, TL., et al.[2021]

In a 12-week pilot study involving 30 veterans with both PTSD and alcohol use disorder, topiramate significantly reduced the frequency and amount of alcohol consumption, as well as alcohol cravings, compared to a placebo.

Topiramate also showed promise in decreasing PTSD symptom severity, particularly hyperarousal symptoms, although it caused temporary cognitive impairment that recovered by the end of the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topiramate treatment of alcohol use disorder in veterans with posttraumatic stress disorder: a randomized controlled pilot trial. Batki, SL., Pennington, DL., Lasher, B., et al.[2021]

Citations

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pmc.ncbi.nlm.nih.gov

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Between-group analyses showed that topiramate reduced frequency of alcohol use and alcohol craving significantly more than placebo and tended to reduce drinking ...

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esmed.org

esmed.org/pharmacotherapy-advances-for-alcohol-use-disorder/

Pharmacotherapy Advances for Alcohol Use Disorder

Clinically, topiramate's effectiveness has been demonstrated in several trials. Johnson et al. showed doses up to 300 mg/day significantly improved drinking ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S1043661824003992

Efficacy of medications for the treatment of alcohol use ...

A Bayesian meta-analysis of topiramate's effectiveness for individuals with alcohol use disorder. J. Psychopharmacol., 37 (2023), pp. 155-163, 10.1177 ...

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ptsd.va.gov/professional/treat/txessentials/clinician_guide_meds.asp

Clinician's Guide to Medications for PTSD

Topiramate has demonstrated mixed results in randomized controlled trials with civilians and Veterans with PTSD. A meta-analysis showed a medium, but not ...

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pmc.ncbi.nlm.nih.gov

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This study of the post-treatment effects of topiramate among individuals with problematic alcohol use showed beneficial effects of the active medication on 4 of ...

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accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2018/201635s018lbl.pdf

TROKENDI XR (topiramate) extended-release capsules, for ...

5.5 Interaction with Alcohol​​ In vitro data show that, in the presence of alcohol, the pattern of topiramate release from TROKENDI XR® capsules is significantly ...