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

Trial Summary

What is the purpose of this trial?

This trial is testing two different sets of medications to see which works better for treating Meniere's disease. One set calms nerves and stabilizes mood, while the other reduces fluid buildup. The goal is to find an effective treatment for patients suffering from severe symptoms like vertigo and hearing loss.

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 data supports the idea that Nortriptyline + Topiramate for Meniere's Disease is an effective treatment?

The available research does not provide specific data on the effectiveness of Nortriptyline + Topiramate for Meniere's Disease. However, it mentions other treatments like Innovar, which helped 58% of patients with long-lasting relief from vertigo. This suggests that while there are effective treatments for Meniere's Disease, the specific combination of Nortriptyline + Topiramate is not directly supported by the data provided. ^{1 2 3 4 5}

What safety data exists for Nortriptyline + Topiramate in treating Meniere's Disease?

The provided research does not contain specific safety data for the combination of Nortriptyline and Topiramate in treating Meniere's Disease. However, it mentions that there has been no randomized controlled trial (RCT) on the efficacy of topiramate for vestibular disorders. Topiramate is known to have adverse effects such as paresthesias and cognitive side effects, with a safety profile based on trials involving epilepsy patients. No specific safety data for Nortriptyline in this context is provided. ^{2 6 7 8 9}

Is the drug nortriptyline + topiramate a promising treatment for Meniere's Disease?

The research does not provide specific evidence about nortriptyline + topiramate for Meniere's Disease, so it's unclear if it's promising. ^{1 3 8 9 10}

Research Team

Hamid Djalilian, MD

Principal Investigator

University of California, Irvine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Evaluating Quality of Life in Patients With Meniere's Disease Treated as Migraine. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Innovar treatment for Meniere's disease. [2019]

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

Meniere's disease in the elderly. [2013]

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

Comparison of second-echelon treatments for Ménière's disease. [2014]

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

Impact of Ménière's disease on quality of life. [2022]

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

Topiramate for the treatment of epilepsy and other nervous system disorders. [2019]

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

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

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

[Pharmacotherapy of Vestibular Disorders, Nystagmus and Cerebellar Disorders]. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of Vestibular Disorders, Nystagmus and Cerebellar Disorders]. [2022]

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

Pharmacotherapy of vestibular and cerebellar disorders and downbeat nystagmus: translational and back-translational research. [2022]