Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT02169830 |
| Other study ID # |
24482_ Vest_Migraine |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 22, 2014 |
| Est. completion date |
October 30, 2019 |
Study information
| Verified date |
March 2021 |
| Source |
St. Louis University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The investigators' study plans to randomize treatment naive patients with vestibular migraine
to an 8 week trial of an escalating dose of either nortriptyline or topiramate followed by an
8 week crossover to the other drug if patient is willing, if patient wants to stay on first
medication we will just continue to follow. During the first 8 weeks if there is an
intolerance to the first drug they can be switched to the other drug at any point and then
followed on that medication for the remainder of the study. Response to therapy will be
quantified by the Migraine Specific Quality of Life (MSQ) and Dizziness Handicap Inventory
(DHI) administered at multiple time points during the study. Three groups of patients that
will be eligible for the study will include 1)Patients with Neuhauser dVM; 2)Patients with
pVM; and 3) Patients with dizziness that falls outside the Neuhauser criteria (non-Neuhauser
vestibular migraine or nNVM).
The investigators' hypothesis is that even patients with dizziness outside of the Neuhauser
dVM and pVM spectrum will respond to treatment for vestibular migraine, and thus likely have
migraine as a cause of their dizziness. Previous research by our group has suggested that
such patients do in fact respond to migraine therapy1. A second goal of the study is to
evaluate the comparative efficacy of nortriptyline and topiramate in the treatment of these
three subgroups of patients with vestibular migraine.
Description:
After identification and trial entry, we will complete intake questionnaire to determine what
type of vestibular migraine category the patients qualify for, a standard of care office
visit with history and physical (Standard of Care) to review symptoms and previous treatment,
patients height and weight (standard of care) will be obtained. Patients will complete a
standard of care audiology assessment, and the following questionnaires: MSQ (Migraine
Symptom Questionnaire) Version 2.1, DHI (Dizziness Questionnaire) , C-SSRS (Columbia Suicide
Severity Rating Scale) and the MoSQ (Motion Sensitivity Questionnaire). All drug naive
patients will undergo a one month lead in of treatment involving dietary and behavioral
control of migraine. Emphasis will be given to cessation of known migraine triggers such as
caffeine, sodas, chocolates, alcohol (especially red wine) and aged cheeses. Patients who
have complete control of their symptoms with diet and behavior modification alone will be
followed for a total of 4 months to determine the durability of symptom relief. Patients who
fail behavior modification during the 2 to 4 month time point can chose to enter the drug
treatment portion of the study, as defined below.
At the one month point, patients will be brought into the clinic for a office visit with
history, physical, and weight checked and will complete MSQ V2.1, DHI, C-SSRS and the MoSQ,
then will be randomization to either nortriptyline or topiramate will occur. Randomization
will occur by opening the lowest numbered of a stack of envelopes which will contain a
randomly preselected card indicating which drug is to be used. The nortriptyline will be
given in an escalating fashion, starting at 25 mg PO qhs for 2 weeks, followed by 50 mg PO
qhs for 2 weeks, and finally 75 mg PO qhs. Patients will be encouraged to use the lowest
effective dose and to self-titrate their medication. Topiramate dosing will be 25 mg PO qhs
for 1 week, followed by 25 mg BID for 1 week, followed by 25 mg in the morning and 50 mg qhs
for 1 week, and finally 50 mg BID. Patients will be allowed considerable leeway in adjusting
their dosage and will be encouraged to stay on the lowest effective dose. Medication will be
provided open label to the patient and paid for through the patients' insurance, as this
intervention falls within current standard practice, and is not investigational.
After two, three and four months on drug patients will be brought into the clinic for a
office visit with history, physical, and weight checked and will complete MSQ V2.1, DHI,
C-SSRS and the MoSQ, then patients will be offered the opportunity to switch to the other
drug. Those patients who wish to switch drugs will first be weaned off their current drug
over a one week time period. Patients who elect to stay on their initial drug will be
followed for a total of four months. Patients who opt for trial of a second drug will then be
started on the second drug via a self-titrating protocol as described above and followed on
that drug for up to 4 months.
The investigators' clinical experience has shown that on occasion patients will refuse to
take more than a few doses of nortriptyline or topiramate due to intolerable side effects.
Such patients will be allowed to immediately initiate therapy with the other drug. The
medication change can be done with a phone call to their pharmacy without an office visit, as
is done in standard of care. Also, patients who already follow a rigorous migraine diet will
be allowed to enter the drug treatment phase immediately. In our experience, such patient
make up less than 5% of the population that presents for treatment of vestibular migraine.
The response to therapy will be assessed during monthly visits with the use of the MSQ, DHI
and MoSQ questionnaires. Patients will be provided compensation for participating in the
study. $60 dollars will be paid to each patient for each month that they participate in the
study. Our goal is to recruit 100 patients over the span of one year.
Data which will be collected include age, sex, height, weight, body mass index (BMI), prior
head MRI or CT, results of vestibular testing, family history of migraine. A careful history
will focus on vestibular migraine comorbidities such as visual scotoma, ability to ride in
the back seat of a car, and history of "sinus pain".
Patients will be identified as having one of three subtypes of vestibular migraine, based on
their symptoms and history as obtained during their initial visit.
Criteria for Neuhauser definite vestibular migraine (dVM): (Neuhauser, 2009):
1. Episodic vestibular symptoms of at least moderate severity.
2. Current of previous history of migraine according to the 2004 criteria of the
International Headache Society (IHS)
3. One of the following migrainous symptoms during 2 or more attacks of vertigo: migrainous
headache, photophobia, phonophobia, visual aura, or other aura
4. Other causes ruled out by appropriate investigations
Criteria for probable vestibular migraine (pVM):
1. Episodic vestibular symptoms of at least moderate severity
2. One of the following A. current or previous history of migraine according to the 2004
criteria of the IHS B. migrainous symptoms during vestibular symptoms C. migraine
precipitants of vertigo in > 50% of attacks: food triggers, sleep irregularities, or
hormonal change D. Response to migraine medications in more than 50% of attacks
3. Other causes ruled out by appropriate investigations
Criteria for (non-Neuhauser vestibular migraine or nNVM) will include those patients who do
not fit the criteria for dVM and pVM but are felt by the investigator to have underlying
migraine as a possible cause of their dizziness. This includes patients with a remote history
of migraines, those with visual auras without headache, those with recurring self-described
"sinus pain" and those with significant motion intolerance, either to their own head motion
or motion in their surroundings.
Due to know drug interactions, patients taking the following medications will be excluded.
Nortriptyline: monoamine oxidase inhibitors (MAO) such as phenelzine. Patients on oral
contraceptives will be asked to use a secondary method as nortriptyline can reduce the
effectiveness of oral contraceptives.
Topiramate: acetazolamide (kidney stones), digoxin
An electronic health record (EPIC) will be used for secure collection of all patient data.
Questionnaires filled out by patients will be scanned into EPIC.
A sample size of 100, which nets 90 subjects into the randomized medication trial (two equal
groups of 45 subjects each), yields a power of 82% to detect a difference in patient-reported
effectiveness/acceptability between the nortriptyline and topiramate groups after two months
of medication use. This sample size estimate assumes 60% of subjects using nortriptyline
report it as effective/acceptable, in contrast to half as many subjects (or 30%) using
topiramate. The power calculation is based on a two-sized Z-test with pooled variance and
targeted significance level (alpha) of 0.05. The expected difference in outcome between the
two groups is based on our prior research (Mikulec, 2012).
Adverse effects of the two drugs will be assessed. Specifically, the following known side
effects will be asked about and recorded.
Nortriptyline: somnolence, weight gain, dry mouth, blurred vision Topiramate: Weight loss,
parasthesias, forgetfulness, nausea, diarrhea, fatigue
The subjects will be allowed to maintain therapy or taper off the drugs. It is anticipated
that those that derive benefit from the drugs will choose to stay on them. All patients will
have the option of remaining under our care outside of the study.
