Nortriptyline + Topiramate for Meniere's Disease

Overseen By Hamid R Djalilian, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, Irvine

Disqualifiers: Pregnancy, Surgery for Meniere's, Psychosis, others

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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two medication combinations to treat Meniere's Disease, a condition causing vertigo, hearing loss, ear ringing, and balance issues. The trial tests nortriptyline (an antidepressant) and topiramate (an anticonvulsant) against another medication combination to determine if they better manage these symptoms. Individuals experiencing active or frequent Meniere's Disease symptoms and who can consistently follow a medication plan might be a good fit for this study. As a Phase 4 trial, this research involves FDA-approved treatments and aims to understand how they can benefit more patients.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What is the safety track record for these treatments?

Research has shown that nortriptyline and topiramate, the treatments under study for Meniere's disease, have been safely used for other conditions. Nortriptyline often treats depression, while topiramate is commonly used for migraines and seizures. Both have strong safety records in these areas.

Although specific safety data for using nortriptyline and topiramate together for Meniere's disease is limited, the study's later phase suggests that earlier research addressed initial safety concerns. This typically indicates that the treatments are generally well-tolerated. However, like any medication, they can have side effects. Common side effects of nortriptyline include dry mouth and dizziness, while topiramate may cause tingling in the fingers or toes.

Participants should consult their healthcare provider about any concerns to better understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the combined use of nortriptyline and topiramate for Meniere's disease because this approach targets the condition's symptoms in a novel way. While traditional treatments often focus on diuretics like hydrochlorothiazide and triamterene to manage fluid buildup, this new combination may offer enhanced symptom control through different mechanisms. Nortriptyline, an antidepressant, and topiramate, an anticonvulsant, are thought to work together to stabilize nerve activity and reduce vertigo and other symptoms associated with Meniere's. This could provide a more comprehensive management strategy for patients who do not respond fully to standard diuretics.

What evidence suggests that this trial's treatments could be effective for Meniere's disease?

Research has shown that nortriptyline and topiramate, which participants in this trial may receive, can help reduce dizziness episodes in people with Meniere's disease. One study found that patients experienced fewer dizziness attacks, decreasing from about 8 to 2 per month on average. This combination also improved quality of life, with patients reporting better scores. Although the FDA has not specifically approved nortriptyline and topiramate for Meniere's disease, they are used to treat similar conditions like migraines, which share symptoms with Meniere's. This suggests they might effectively manage symptoms. ^{2 5 6 7 8}

Who Is on the Research Team?

Hamid Djalilian, MD

Principal Investigator

University of California, Irvine

Are You a Good Fit for This Trial?

This trial is for adults aged 25-85 with active or frequent Meniere's Disease who can take medication regularly and attend study visits. They must be able to read and write English to consent. Excluded are pregnant women, those with a history of surgery for Meniere's, adverse reactions to the study medications, concerning medical conditions, psychosis, neurological tumors, or contraindications preventing safe use of the drugs.

Inclusion Criteria

Subject must be compliant with the medication and attend study visits

Must be able to read and write in the English language to provide consenting

I am between 25 and 85 years old.

Exclusion Criteria

I am not allergic or unable to take any of the trial medications.

Pregnancy will result in automatic exclusion from the study. A urine pregnancy test to rule out pregnancy for all women who are of childbearing potential

I have a brain or spinal cord tumor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nortriptyline plus topiramate or hydrochlorothiazide plus triamterene for 8 weeks, with possible dosage increases based on symptom improvement

8 weeks

Weekly visits for symptom monitoring and dosage adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• nortriptyline + topiramate

Trial Overview

The trial tests if migraine medications nortriptyline and topiramate can treat Meniere's Disease symptoms like vertigo and hearing loss. There are no FDA-approved treatments for this condition yet; these drugs have shown promise in clinical practice.

How Is the Trial Designed?

Group I: nortriptyline + topiramate Experimental Treatment 1 Intervention

Nortriptyline (starting dose 7.5 mg) plus Topiramate (starting dose 10 mg) with appropriate dosage increase as necessary

Group II: hydrochlorothiazide + triamterene + placebo Active Control 1 Intervention

hydrochlorothiazide (starting dose 25 mg) plus triamterene (starting dose 37.5 mg) with placebo being added in case of a dosage increase

nortriptyline + topiramate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Pamelor + Topamax for:

• Migraine prophylaxis
• Seizure control
• Depression

Approved in European Union as Nortriptyline + Topiramate for:

• Migraine prophylaxis
• Seizure control
• Depression
• Neuropathic pain

Approved in Canada as Nortriptyline + Topiramate for:

• Migraine prophylaxis
• Seizure control
• Depression

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Published Research Related to This Trial

Corticosteroids may help improve recovery in acute unilateral vestibulopathy, but there isn't enough evidence to make a strong recommendation for their use.

Higher dosages of betahistine are suggested for Menière's disease due to insufficient evidence supporting lower doses, and it has been shown in animal studies to increase cochlear blood flow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of Vestibular Disorders, Nystagmus and Cerebellar Disorders]. Feil, K., Böttcher, N., Kremmyda, O., et al.[2019]

Corticosteroids may help improve recovery in acute unilateral vestibulopathy, but there isn't enough evidence to make a strong recommendation for their use.

Higher dosages of betahistine are suggested for Menière's disease due to insufficient evidence supporting lower doses, and it has been shown in animal studies to increase cochlear blood flow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of Vestibular Disorders, Nystagmus and Cerebellar Disorders]. Feil, K., Böttcher, N., Kremmyda, O., et al.[2022]

In a study of 27 patients with Meniere's disease, 25 completed follow-up questionnaires showing a significant improvement in quality of life (QOL) after migraine prophylaxis therapy, with an average QOL score increase of 25 points (P = .02).

92% of patients reported improvements across all measured aspects of QOL, suggesting that migraine prophylactic medications can be an effective treatment for Meniere's disease, especially for those who did not respond to diuretic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating Quality of Life in Patients With Meniere's Disease Treated as Migraine. Ghavami, Y., Haidar, YM., Moshtaghi, O., et al.[2018]

Corticosteroids may help improve recovery in acute unilateral vestibulopathy, but there isn't enough evidence to make a strong recommendation for their use.

Higher dosages of betahistine are suggested for Ménière's disease based on animal studies showing increased cochlear blood flow, as current evidence does not support lower dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of vestibular and cerebellar disorders and downbeat nystagmus: translational and back-translational research. Strupp, M., Zwergal, A., Feil, K., et al.[2022]

Topiramate (TPM) has been safely administered to 1,809 individuals, primarily adults with partial-onset seizures, with long-term treatment data showing no significant abnormalities in clinical laboratory tests over periods of up to 5.3 years.

Common side effects were mostly related to the central nervous system and occurred more frequently at higher doses, while mild weight loss and a low incidence of kidney stones were also noted, indicating a generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of topiramate: adverse events and relationships to dosing. Shorvon, SD.[2022]

Patients with Ménière's disease experience a significant reduction in health-related quality of life, with a Quality of Well-being score indicating a 43.9% loss compared to symptom-free individuals.

The study found that patients had notably low physical and mental health scores, with many showing signs of clinically significant depression, highlighting the severe impact of the disease on their daily lives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Ménière's disease on quality of life. Anderson, JP., Harris, JP.[2022]

In a study of patients with intractable vertigo from Meniere's disease who did not respond to standard treatments, 58% experienced long-lasting relief from vertigo after treatment with Innovar over a follow-up period of 2-8 years.

Innovar was found to be a safe and cost-effective second-line therapy, with no negative impact on hearing, and factors such as being male, having fluctuating hearing, and being in the early stages of the disorder were associated with better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovar treatment for Meniere's disease. Gates, GA.[2019]

Topiramate, originally developed as a diabetes medication, has proven effective as an anticonvulsant since its approval in 1996, showing broad efficacy in treating epilepsy, including in children.

In addition to epilepsy, topiramate is effective for migraine prevention and has potential benefits for weight loss, substance dependence, and other neurological and psychiatric conditions, although it can cause side effects like paresthesias and cognitive issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topiramate for the treatment of epilepsy and other nervous system disorders. van Passel, L., Arif, H., Hirsch, LJ.[2019]

Antivertiginous medications like betahistine and cinnarizin are effective for treating Menière disease in elderly patients, offering good results with minimal side effects, making them safer options compared to stronger vestibular suppressors.

Surgical options, such as labyrinthectomy and selective vestibular neurectomy, can be considered for severe cases, particularly for managing drop attacks, which pose significant risks for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meniere's disease in the elderly. Vibert, D., Caversaccio, M., Häusler, R.[2013]

In a study of 60 patients with Ménière's disease who did not respond to initial treatments, the Meniett device, endolymphatic sac decompression, and intratympanic gentamicin injections showed no significant differences in effectiveness for controlling vertigo or preserving hearing over a minimum of two years.

All three treatment options had similar outcomes regarding the need for further surgical intervention (labyrinthectomy) and the duration of symptom relief, indicating that patients may choose any of these options without expecting a significant difference in results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of second-echelon treatments for Ménière's disease. Basura, GJ., Lin, GC., Telian, SA.[2014]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05582837

Treatment of Meniere's Disease With Migraine Medications

This study is 8 weeks in duration. There are two arms in the experiment: the first is nortriptyline (7.5 mg) plus topiramate (10 mg), the second is ...

2.

withpower.com

withpower.com/trial/phase-4-mnire-7-2022-a69bf

Nortriptyline + Topiramate for Meniere's Disease

The available research does not provide specific data on the effectiveness of Nortriptyline + Topiramate for Meniere's Disease. However, it mentions other ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9679161/

Vestibular migraine treatment: a comprehensive practical review

The before-and-after analysis for the combined group found a reduction in mean monthly vertigo frequency (8.1–2.3 attacks per month, P < 0.01), mean headache ...

4.

connect.careboxhealth.com

connect.careboxhealth.com/en-US/trial/listing/379739

Treatment of Meniere's Disease With Migraine Medications

Subjective improvement in Meniere's Disease Outcomes ... Treatment of Meniere&#39;s Disease With Nortriptyline-Topiramate Stepwise Regimen: A Randomized Double- ...

5.

journals.sagepub.com

journals.sagepub.com/doi/10.1177/0003489418799107

Evaluating Quality of Life in Patients With Meniere's ...

The mean change in quality of life score was 25 ± 16 points (range, –3 to 55). There was significant improvement in all but 3 subitems of the ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05582837

Treatment of Meniere's Disease With Migraine Medications

This study is 8 weeks in duration. There are two arms in the experiment: the first is nortriptyline (7.5 mg) plus topiramate (10 mg), the second is ...

7.

ucihealth.org

ucihealth.org/clinical-trials/indp-21-6445

Treatment of Meniere s Disease with Nortriptyline- ...

This study is 8 weeks in duration. There are two arms in the experiment: the first is nortriptyline (7.5 mg) plus topiramate (10 mg), ...

8.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/30/NCT02169830/Prot_SAP_000.pdf

Protocol # 24482

The primary goal of the study is to evaluate the comparative effectiveness of migraine diet, nortriptyline and topiramate in the treatment of ...