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

Trial Summary

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}

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.

Research Team

Charles Marmar, MD

Principal Investigator

NYU Langone Health

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.

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
• 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.

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 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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

References

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

Treatment of civilian and combat-related posttraumatic stress disorder with topiramate. [2018]

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

[Topiramate for the treatment of post traumatic stress disorder. A case study]. [2018]

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]

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]

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]

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]

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

USL255 extended-release topiramate: dose-proportional pharmacokinetics and tolerability in healthy volunteers. [2021]

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]