The Role of Migraine Prophylaxis Agent Topiramate in Treating Patients With Sudden Sensorineural Hearing Loss
Phase: PHASE2
Conditions: Sudden Deafness, Sudden Sensorineural Hearing Loss
Sponsor: Chang Gung Memorial Hospital

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden sensorineural 
hearing loss                                                                                                                                                   Version: 6 
                                                                                                                                                             Date: 20220812 
 
 
 
 
CLINICAL STUDY PROTOCOL 
 
〔PROTOCOL TITLE〕 
The role of migraine prophylaxis agent topiramate in treating patients with sudden 
sensorineural hearing loss 
 
VERSION NO.6 
 DATES (20220812) 
 
 
INVESTIGATORS 
SITES 
 
NCT05403229 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden sensorineural 
hearing loss                                                                                                                                                   Version: 6 
                                                                                                                                                             Date: 20220812 
 
Table of Contents 
 
Section 
Page 
1. Synopsis ...................................................................................................................................1 
2. Introduction and Rationale ............................................................................................................. 
3. Objectives and Endpoints .......................................................................................................... 
3.1. Study Objectives ..................................................................................................................  
3.2. Study endpoints ...................................................................................................................  
4. Study Design.............................................................................................................................. 
4.1. Overall Design (Flow Chart) ...............................................................................................  
4.2. Number of Patients ...............................................................................................................  
4.3. Schedule of Activities (Time-Event scheme) ......................................................................  
5. Study Population ........................................................................................................................ 
5.1. Inclusion Criteria ..................................................................................................................  
5.2. Exclusion Criteria ................................................................................................................  
5.3. Withdrawal criteria .......................................................................................................................... 
6. Treatments ................................................................................................................................. 
6.1. Treatments Administration ..................................................................................................  
6.2. Concomitant Therapy ......................................................................................................  
7. Efficacy Assessments ............................................................................................................ 
8. Safety Assessments 
9. Adverse Event reporting 
9.1. Definition and reports of Adverse Events........................................................................  
9.2. Adverse event follow-up ..................................................................................................  
10. Criteria for the termination of the trials 
11. Statistical Considerations 
11.1. Sample Size Determination ............................................................................................ 
11.2. Planned Statistical methods of analysis .......................................................................... 
11.2.1. Efficacy analyses ...................................................................................................... 
11.2.2. Safety analyses ......................................................................................................... 
11.2.3. Additional analyses .................................................................................................. 
11.2.4. The level of significance .......................................................................................... 
11.2.5. Analysis Population .................................................................................................. 
12. Direct access to source data/documents 
13. Ethical considerations 
14. Data handling and keeping 
15. Financing and Insurance 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden sensorineural 
hearing loss                                                                                                                                                   Version: 6 
                                                                                                                                                             Date: 20220812 
16. References.............................................................................................................................. 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden 
sensorineural hearing loss                                                                                                                                                   
Version: 6 
                                                                                                                                                             Date: 20220812 
 
1. Synopsis 
 
 
Protocol Title： 
     The role of migraine prophylaxis agent in treating patients with sudden 
sensorineural hearing loss – A randomized controlled trial 
Study Objectives： 
    To understand the efficacy of migraine prophylaxis agent “topiramate” in treating 
patients with sudden sensorineural hearing loss 
Investigational product(s)： 
Topiramate 
Development Phase：⃞ I   ⃞II    ⃞III     ⃞IV    ⃞others______   V  not applicable 
    Study Design： 
1. v Experimental Group 
v Control Group ：  □  Placebo  
□ Study Drug  (Name、Dose、Usage)  __________________ 
v Other __standard systemic steroid with/without intratympanic steroid_ 
2. Blinding：v Open  □ Evaluator-blind  □ Single-blind(patient)  □ Double-blind(patient+PI)    
□ Double Dummy   □ Other ______________ 
3.  Randomization:  v Yes   □ No 
4. □ Parallel design   □ Crossover design   □ Other ____________   v Not applicable 
5.  Treatment Period：_____6 weeks______  □ Not applicable 
  6.  Study Period: _______1____year   (or From DD/MM/YYYY to DD/MM/YYYY) 
6. Dose adjustment：v Mandatory     □ Selectively       □ No        □ Not applicable 
7. Study location：□ Single v Multi-center  □  Global  
Endpoints (Outcome measure)： 
 
1. Primary endpoint: 
The improvement rate and gain of pure tone audiometry (compare day 0 and day 84) 
2. Secondary endpoints: 
        The improvement rate and gain of word recognition score (compare day 0 and day 84) 
       The improvement rate and gain of pure tone audiometry (compare day 0 and day 56) 
3. Exploratory endpoints (if any): nil 
Inclusion/Exclusion Criteria： 
Inclusion criteria 
1.Age > 20 
2. Confirmed diagnosis of unilateral sudden sensorineural hearing loss(SSNHL)  
3. Treatment started 14 days within onset of SSNHL 
 
Exclusion criteria 
1. Previous SSNHL history 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden 
sensorineural hearing loss                                                                                                                                                   
Version: 6 
                                                                                                                                                             Date: 20220812 
2. Previous middle ear disorder such as chronic otitis media, or previous ear surgery 
3. Meniere’s disease and fluctuating hearing loss patients 
4. Pregnancy or trying to become pregnant 
5. Leukemia, hemodialysis, and patients who received chemotherapy before. 
6. Previous head and neck radiotherapy 
7. Cerebellopontine (CP) angle tumor such as vestibular schwannoma 
8. Patients with moderate to severe hepatic insufficiency 
9. Patients with major depression disorder or suicide attempt 
10. Patients with glaucoma 
 
Study Procedures： 
         
1. Expected inclusion patient number (enrolled number: 140; evaluable number: 112) 
The participants would be divided into two group, half in the experimental group and the other 
half in the control group.  
2. All patients will receive audiometry examination, laboratory examination, magnetic resonance 
imaging of brain or auditory brainstem response at the first visit. Then the patient would be 
followed at the clinic weekly till the sixth week. Audiometry examination will be arranged 
during the first week and then monthly till 12 weeks. 
3. As for the treatment, the control group will receive systemic steroid with/without intratympanic 
steroid for 2 weeks as the standard therapy for sudden sensorineural hearing loss. The 
experimental group will receive systemic steroid with/without intratympanic steroid for 2 weeks 
and simultaneously oral topiramate for 6 weeks.  
4. There will be no specimen collection in this study. 
5. The patients’ gender, age, initial and final hearing threshold, laboratory examination result, 
audiometry result and symptoms will be collected.  
 
Concomitant Treatments：  □not applicable 
1. Concomitant Therapy：Prescribe systemic steroid with/without intratympanic steroid 
      2. Prohibited Therapy：nil 
Statistical Methods： 
1. Main study Hypothesis： V Equality  □ Superiority  □ Non-inferiority  
   ⃞ Equivalence   □ Other ________ 
2. Estimated Sample Size：Anticipated enrolled size___140____，Estimated evaluable number 
__112____ 
                                               Anticipated enrolled size in our center___45____，Estimated 
evaluable number in our center___40___ 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden 
sensorineural hearing loss                                                                                                                                                   
Version: 6 
                                                                                                                                                             Date: 20220812 
 
*Missing rate =10%, thus the enrollment size is 112/0.9=125 
*Missing rate =20%, thus the enrollment size is 112/0.8=140 
3. Efficacy assessment group：  V Intent-to-treat (ITT)   □ Per-Protocol (PP)   
                                                 □ Other ________ 
4. Interim analysis： □ Yes    V No 
5. Statistical methods : t test will be performed to compare pre- and posttreatment audiometric 
measurements. Chi-square and independent sample t test will be used to compare categorical 
and numerical variables between the two groups, respectively. 
6. Handling of Missing Data : The cases with missing data will be omitted. The remaining data 
will be analyzed to determine the efficacy of study drug. 
 
 
2. Introduction and Rationale 
 
2.1 Investigational product(s) 
Topiramate is an anticonvulsant agent with multiple mechanism. The ability of preventing 
migraine attack was demonstrated by previous randomized controlled trials. It is an oral 
tablet with well tolerability. When using this agent to prevent migraine, the dosage started 
from 25mg per day and could be titrated up to 100mg per day.  
 
2.2 Animal and preclinical study data 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden 
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Not applicable 
2.3 Clinical data 
 
Migraine and sudden sensorineural hearing loss(SSNHL) are two related disorder. Systemic 
steroid is usually used to treat SSNHL but the role of migraine prophylaxis medication remained 
unknown. Mehdi Abouzari et al. found a better improvement when combining topiramate and 
nortriptyline with steroid in a retrospective study. However, a prospective study with 
randomization is needed to elucidate the efficacy of these agents.  
2.4 Risks / benefits Assessment 
 
Topiramate is a safe medication that has been already used in treatment of migraine 
prophylaxis and seizure. The potential adverse effects of topiramate includes mild 
disturbance in taste, loss of appetite, paresthesia of distal extremities, and increase fetal oral 
cleft risk. Therefore, children, adolescents and pregnant women were excluded from this 
study.  
The possible benefit from using topiramate in this study is the possible better audiometry 
improvement. 
2.5 Regulatory 
This study will be conducted in compliance with the protocol approved by the Institutional 
Review Board, and according to Good Clinical Practice standards.  No deviation from the 
protocol will be implemented without the prior review and approval of the IRB except where 
it may be necessary to eliminate an immediate hazard to a research subject.  In such case, the 
deviation will be reported to the IRB as soon as possible. 
 
3.  Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
1.To understand the treatment effects 
of Topiramate for sudden 
sensorineural hearing loss 
1.Pure tone audiometry 
improvement (day 0 and day 84) 
Secondary 
1.To understand the additional 
treatment effects of topiramate for 
sudden hearing loss events 
1. word recognition score 
improvement (compare day 0 
and day 84) 
2. The improvement rate and gain 
of pure tone audiometry 
(compare day 0 and day 56) 
 
4. Study Design 
 
4.1 Overall Design 
 
This is a clinical study using medication approved and currently prescribed in the clinic. The 
included patients were those who came to clinic and was diagnosed as SSNHL within 14 days of 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden 
sensorineural hearing loss                                                                                                                                                   
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onset. Those patients were asked whether they agreed to participate this clinical trial. Patients who 
were diagnosed as SSNHL but was later found to be other disease such as Meniere’s disease, CP 
angle tumor will be excluded from this study. 
 
The involved patients were randomized divided into two groups. (The randomization was based on 
computer-generated random numbers.) 
Both groups received systemic steroid with/without intratympanic steroid. The experimental group 
receive additional oral topiramate for 6 weeks. 
Follow-up time is 3 months.  
 
This study is multi-center.  
Location of the study is performed at Chang gung memorial hospital Linkou branch, Taipei branch, 
Taoyuan branch, and New Taipei Municipal Tucheng Hospital. 
 
Flow Chart： 
 
 
 
 
 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden 
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4.2 
Number of Patients 
Enrolled number : 140  
Failed during screening : 10 
Drop-out number : 28 
Estimated evaluable number : 112 ( experimental group 56, control group 56 ) 
 
4.3 
Schedule of Activities 
 
Time-Event scheme(評估時程表): 
 
The physician confirm that the patient meets the inclusion criteria at the 
initial visit (day 0). Then the patients would be asked if he/she is willing to 
participate into this clinical trial. If the patient agreed, then medical history 
taking, audiometry and lab examination, MRI or ABR examination will be 
arranged at same time. He/she will be randomized into either experimental 
arm or control arm. The treatment will be started immediately. The blood test 
will be performed at first visit and the data will be checked at day 7. Patients 
in both arms would follow up at our clinic at day 7,14,21,28,56, and 84. Pure 
tone audiometry and speech audiometry will be followed at day 56 and 84. 
Symptoms and adverse effects (safety monitoring) will be followed up at day 
7,14,21,28, and 56.  
 
5. Study Population 
 
5.1 Inclusion Criteria 
         
Inclusion criteria: 
(1) Age > 20 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden 
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 Date: 20220812 
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(2) Confirmed diagnosis of unilateral sudden sensorineural hearing loss(SSNHL)  
(3) Treatment started 14 days within onset of SSNHL 
 
The diagnostic criteria of SSNHL: 
A subset of sudden hearing loss that (a) is sensorineural in nature, (b) occurs within a 72-hour 
window, and (c) consists of a decrease in hearing of >= 30 decibels affecting at least 3 consecutive 
frequencies. 
 
The diagnostic criteria of vestibular migraine: 
A. At least 5 episodes with vestibular symptoms of moderate or severe intensity, lasting 5 min to 
72 hours 
B. Current or previous history of migraine with or without aura according to the International 
Classification of Headache Disorders (ICHD) 
C. One or more migraine features with at least 50% of the vestibular episodes: 
– headache with at least two of the following characteristics: 
one sided location, pulsating quality, moderate or severe pain intensity, aggravation by routine 
physical activity 
– photophobia and phonophobia, 
– visual aura 
D. Not better accounted for by another vestibular or ICHD diagnosis 
 
5.2 Exclusion Criteria 
 
Exclusion criteria: 
(1) Previous SSNHL history 
(2) Previous middle ear disorder such as chronic otitis media, or previous ear surgery 
(3) Meniere’s disease and fluctuating hearing loss patients 
(4) Pregnancy or trying to become pregnant 
(5) Leukemia, hemodialysis, and patients who received chemotherapy before. 
(6) Previous head and neck radiotherapy 
(7) CP angle tumor such as vestibular schwannoma 
(8) Patients with moderate to severe hepatic insufficiency 
(9) Patients with major depression disorder or suicide attempt 
(10) Patients with glaucoma 
 
5.3 Withdrawal criteria 
Withdraw from the study: 
Participants of this study can withdraw from this study at any time when the patient disagree the 
consent, or had intolerable adverse effects after medication, or could not follow the treatment 
protocol. 
The data of the withdraw patients will be excluded from the audiometry analysis. The reason of 
withdrawal would be analyzed and reported. 
 
6. Treatments 
 
6.1.Treatment Administration 
 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden 
sensorineural hearing loss                                                                                                                                                   
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Both experimental group and control group will receive systemic steroid with/without 
intratympanic steroid as the standard treatment for sudden sensorineural hearing loss. The total 
duration of systemic steroid is 2 weeks.  
As for the experimental group, topiramate 25 mg orally before bedtime with weekly escalation of 
25 mg up to 100 mg. More specifically, the patient will receive 25mg daily at first week. 
Then the dose will be titrated up to 50mg in the second week, 75mg in the third week, and 
100mg daily during the 4-6 weeks. 
 
The dose of topiramate will be half in patients with renal insufficiency (ClCR ≤ 70 mL/min).  
 
 
 
6.2. Concomitant Therapy 
Both experimental group and control group will receive systemic steroid with/without 
intratympanic steroid as the standard treatment for sudden sensorineural hearing loss. 
Hyperbaric oxygen therapy, a common therapy for sudden sensorineural hearing loss, is also 
allowed in these patients.  
       
7. Efficacy Assessments 
      The evaluation of hearing ability is performed by pure tone audiometry, speech audiometry and 
word recognition test(WRS). 
      The audiometry will be arranged during the first clinic visit and followed at day 56 and day 84. 
Then the differences of the pre- and posttreatment audiometry will be evaluated.  
     The pure-tone average(PTA) calculated using 0.5-, 1-, 2-, and 3-kHz air conduction 
thresholds. The WRS is presented as percentage. The treatment efficacy compares the 
difference of PTA and WRS before and after treatment. 
 
8. Safety Assessments 
        The most frequent side effects of the study drug are mild disturbance in taste, appetite, and 
paresthesia of distal extremities. There are no major adverse events reported in previous clinical 
trials. Those symptoms will be monitored and recorded during each clinical follow-up (from the 
first clinic to the end of follow-up after 3 months). 
 
 
9. Adverse event reporting 
 Bang-Yan, Zhang will report SAEs to the IRB of Chang Gung Medical Foundation 
according to the Serious Adverse Event Reporting Procedures and Guidelines as posted in 
the Clinical Trials Resource on the website of Chang Gung Medical Foundation IRB. SAE 
reports to the IRB should include the following information when calling the Medical 
Monitor: 
• Date and time of the SAE 
• Date and time of the SAE report 
• Name of reporter 
• Call back phone number 
• Affiliation/Institution conducting the study 
• Protocol number 

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• Title of protocol 
• Description of the SAE, including attribution to drug and expectedness    
 
 
9.1 Definitions and reports of Adverse Events 
All adverse events that occur after the informed consent is signed (including run-in) must be 
recorded on the adverse event CRF (paper and/or electronic) whether or not related to study 
agent. AE Data Elements including: 
• AE reported date 
• AE Verbatim Term 
• CTCAE Term (v 5.0) 
• Event onset date and event ended date 
• Severity grade 
• Attribution to study agent (relatedness) 
• Whether or not the event was reported as a Serious Adverse Event (SAE) 
• Action taken with the study agent 
• Outcome of the event 
• Comments 
 
Identify the adverse event using the NCI Common Terminology Criteria for Adverse Events 
(CTCAE) version 5.0.  The CTCAE provides descriptive terminology and a grading scale for 
each adverse event listed. 
 
AEs will be assessed according to the CTCAE grade associated with the AE term.  AEs that 
do not have a corresponding CTCAE term will be assessed according to their impact on the 
participant’s ability to perform daily activities as follows: 
 
 
Grade 
Severity 
Description  
1 
Mild 
• 
Barely noticeable, does not influence functioning 
• 
Causing no limitations of usual activities 
2 
Moderate 
• 
Makes participant uncomfortable, influences functioning 
• 
Causing some limitations of usual activities 
3 
Severe 
• 
Severe discomfort, treatment needed 
• 
Severe and undesirable, causing inability to carry out 
usual activities 
4 
Life threatening 
• 
Immediate risk of death 
• 
Life threatening or disabling 
5 
Fatal 
• 
Causes death of the participant 
 
The possibility that the adverse event is related to study drug will be classified as one of the 
following:  not related, unlikely, possible, probable, definite. 
  
DEFINITION of Serious Adverse Events: ICH Guideline E2A and GCP of Taiwan define 
serious adverse events as those events, occurring at any dose, which meet any of the 
following criteria: 
• Results in death 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden 
sensorineural hearing loss                                                                                                                                                   
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• Is life threatening (Note: the term life-threatening refers to an event in which the 
patient was at risk of death at the time of the event; it does not refer to an event 
which hypothetically might have caused death if it were more severe). 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital abnormality/birth defect 
• Events that may not meet these criteria, but which the investigator finds very 
unusual and/or potentially serious, will also be reported in the same manner. 
 
9.2 Adverse event follow-up 
 
All AEs, including lab abnormalities that in the opinion of the investigator are clinically 
significant, will be followed according to good medical practices and documented as such. 
Site staff should send follow-up reports as requested when additional information is available.  
Additional information should be entered on the IRB of Chang Gung Medical Foundation of 
SAE form in the appropriate format.  Follow-up information should be sent to Chang Gung 
Medical Foundation IRB as soon as possible according to IRB’s Serious Adverse Event 
Reporting Procedures and Guidelines.  
 
10. Criteria for the termination of the trial 
          
The trial can be ended before the planned end date because of evidence of adverse effects 
(harm), or likelihood of failing to reject the null hypothesis (futility) 
 
 
11. Statistical Considerations 
 
t test will be performed to compare pre- and posttreatment audiometric measurements. Chi-
square and independent sample t test will be used to compare categorical and numerical 
variables between the two groups, respectively. 
 
11.1 Sample size Determination 
 
The study will be powered to approximately 80% assuming a standard deviation of 13 at 
an alpha of 0.05. The number of patients required to observe a 5dB difference between the 
experimental group and control group is about 56 patients in each group if the superiority 
margin at 0.05. The total estimated patients number required is 112. Consider the patient 
with incomplete data and drop-out rate of 20%, the total estimated number of sample size 
is about 140. 
 
11.2 Planned Statistical methods of analysis 
Statistical analysis  
Quantitative variables will be presented as mean± standard deviation (SD) and categorical 
variables will be presented as proportions. Paired samples t test will be performed to compare 
pre- and posttreatment audiometric measurements. Chi-square and independent sample t test 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden 
sensorineural hearing loss                                                                                                                                                   
Version:6 
 Date: 20220812 
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will be used to compare categorical and numerical variables between the two groups, 
respectively. 
The data will be evaluated at the end of study. The expected study period is 1 year. 
There will be an interim analysis. 
 
 
11.2.1 Efficacy analysis 
The audiometry data will be evaluated at the end of study. Pure tone average (PTA) was 
measured in accordance with the Committee on Hearing and Equilibrium Guidelines, 
utilizing thresholds at frequencies of 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz. The hearing 
recovery is defined as a more than 10 dB hearing gain.   
 
11.2.2 Safety analysis 
         The medication used in this study is well studied in the previous clinical trials. The possible 
adverse effects of the medication will be monitored during each follow-up. The adverse effects of 
the medication will be analyzed at the end of study. 
 
11.2.3 Additional analysis 
        Nil 
 
11.2.4 The level of significance 
A p-value less than 0.05 was considered significant and was denoted by *. 
 
11.3 Analysis Population 
        All eligible participants will be included in the analyses. If the participant wishes to withdraw due to 
any reason after enrollment, the data will also be reported.  
 
 
11.4 Procedure for accounting for missing, unused and spurious data 
The incomplete clinical data and sequencing data with poor quality will be excluded in 
the study. 
 
11.5 Procedures for reporting any deviation(s) from the original statistical plan 
Any deviation(s) from the original statistical plan should be described and justified in 
protocol and/or in the final report, as appropriate. 
 
12. Direct access to source data/documents 
Investigators permit IRB to access to the source data of experiment for trial-related 
monitoring, audits, and regulatory inspection. 
 
13. Ethical considerations 
           This study will be conducted according to Taiwan and international standards of Good 
Clinical Practice for all studies.  Applicable government regulations and Chang Gung 
Medical Foundation research policies and procedures will also be followed. 

Protocol: The role of migraine prophylaxis agent topiramate in treating patients with migraine and sudden 
sensorineural hearing loss                                                                                                                                                   
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This protocol and any amendments will be submitted to the Chang Gung Medical Foundation 
Institutional Review Board (IRB) for formal approval to conduct the study.  The decision of 
the IRB concerning the conduct of the study will be made in writing to the investigator.   
 
All subjects for this study will be provided a consent form describing this study and 
providing sufficient information for subjects to make an informed decision about their 
participation in this study.  This consent form will be submitted with the protocol for review 
and approval by the IRB.  The formal consent of a subject, using the IRB-approved consent 
form, will be obtained before that subject is submitted to any study procedure.  This consent 
form must be signed by the subject or legally acceptable surrogate, and the investigator-
designated research professional obtaining the consent.  
 
14. Data handling and keeping 
Clinical data will be collected in Chang Gung Medical Foundation. The sequencing data 
will be stored in computers of laboratory with an electronic encryption. The clinical and 
source data can only be assessed by clinical doctors and investigators of the study. The 
participants will be identified by a unique trial specific number and/or code in any database.  
The name and any other identifying detail will NOT be included in any trial data electronic 
file. 
 
15.   Financing and Insurance 
       There is no conflict of interest in this study. The research funding sources is from CMRP. 
The medication used in this study is prescribed commonly in the clinic and no additional 
insurance is applied for the participants.  
 
16. References 
    The mechanism of migraine and sudden hearing loss is not fully understood. Neurovascular 
damage or dysfunction are proposed etiology but could be the result of disease. Currently, many 
clinical trials have been done and the main focus is to prevent migraine attack. But the effects on 
hearing recovery after sudden hearing loss remained unknown. Mehdi Abouzari et al. reported a 
better low tone hearing recovery when combining adjuvant migraine medications with 
conventional steroid therapy. This retrospective study utilized topiramate and nortriptyline in the 
experimental group. However, the true treatment efficacy of these agents remained unknown. 
Therefore, a prospective study using single migraine prophylaxis agent in this condition may 
better elucidate the effects of hearing recovery. 
 
Reference :  
Abouzari M, Goshtasbi K, Chua JT, Tan D, Sarna B, Saber T, Lin HW, Djalilian HR. Adjuvant 
Migraine Medications in the Treatment of Sudden Sensorineural Hearing Loss. Laryngoscope. 
2021 Jan;131(1):E283-E288. doi: 10.1002/lary.28618. Epub 2020 Apr 3. PMID: 32243585; 
PMCID: PMC8011356.