Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT06417684 |
| Other study ID # |
240605 |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
Early Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
June 19, 2024 |
| Est. completion date |
June 2026 |
Study information
| Verified date |
June 2024 |
| Source |
Vanderbilt University Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Vestibular migraine (VM) is one of the most common causes of vertigo attacks, affecting 1 -
5% of people. People with vestibular migraine have lower quality of life compared to others
and some may experience completely debilitating symptoms. Symptoms include vertigo, nausea,
head motion-induced dizziness, unsteadiness, balance problems, and lightheadedness. There is
evidence the medication amitriptyline in isolation and also our lifestyle modification
intervention in isolation can each help reduce symptoms of dizziness and headache in patients
with VM. However, these data are observational and subject to various types of bias. The
purpose of the current investigation is to determine outcomes from each intervention using
randomized allocation of participants diagnosed with VM into either the amitriptyline arm or
the lifestyle modification arm. The investigators will measure for change in dizziness using
the Dizziness Handicap Inventory (DHI) and for change in headache using the Headache
Disability Inventory (HDI). For participants in the lifestyle modification arm, the
investigators will also measure for change in lifestyle factor to determine improvement on
those intervention factors. Measures will be obtained pre-intervention to establish baseline,
at 30 days, 60 days, and 90 days. the investigators will also re-survey participants one year
after initiation of intervention to determine adherence and status.
Description:
1.0 Background
Vestibular migraine (VM) is one of the most common causes of vertigo attacks, affecting 1 -
5% of people. People with vestibular migraine have lower quality of life compared to others
and some may experience completely debilitating symptoms. Symptoms include vertigo, nausea,
head motion-induced dizziness, unsteadiness, balance problems, and lightheadedness. Most
reports of vestibular migraine management have focused on treatment with medications;
however, the investigators have shown that intervention with lifestyle modification is also
effective.
1.1 Lifestyle Modification for Vestibular Migraine Our lifestyle modification intervention
focuses on improving four factors: avoidance of dietary triggers, regulated mealtimes,
restful sleep, and exercise. By controlling these factors that are often exacerbating for
patients with VM, the investigators decrease the symptoms of dizziness and headache. In our
studies, the investigators measure outcomes with two validated instruments, the dizziness
handicap inventory (DHI) and the headache disability index (HDI). Using this approach, the
investigators have found significant improvement within two weeks of starting the lifestyle
modification intervention. Further, the investigators have seen that 44.7 - 59% of
participants experienced significant improvement in dizziness within 30 days while 13.2 -
18.5% of patients experienced significant improvement in headache. The investigators have
shown that 39% of participants experience significant reduction in dizziness and 18% in
headache at 105 days of lifestyle modification intervention (Roberts et al, 2021). The
investigators have even seen that 25% of participants continue to have significant benefit of
lifestyle modification on dizziness at 371 days. Only 2.6 - 3.6 % of patients report worsened
dizziness and no one has reported worse headache. The investigators were also able to
determine that restful sleep was the modifiable factor most important for improvement when
participant group data is evaluated. This lifestyle modification intervention appears
effective and safe with long-term outcomes better than reported for oral preventive migraine
medication which has adherence rates around 25% at six months and 14% at one year.
1.2 Amitriptyline for Vestibular Migraine Amitriptyline is a medication that is mentioned
often as a preventive treatment for VM. This medication is a tricyclic antidepressant (TCA)
that blocks the reuptake of both serotonin and norepinephrine neurotransmitters. This
medication is considered more sedating and has greater anticholinergic properties than other
TCAs. For depression, therapeutic action begins in 2 - 4 weeks. In a retrospective study,
Salmito et al. (2017) reported significant improvement in vestibular symptoms and headache
for 13 patients treated with amitriptyline 25 mg measured at three months. The authors also
included lifestyle modification so this is not solely a medication mediated effect.
Domínguez-Durán et al. (2020) used 10 mg of amitriptyline daily, one hour before sleeping, in
18 of their patients with VM. Two participants stopped or did not take the medication as
directed. The authors reported significant improvement in dizziness and headache at the
five-week follow-up appointment. 12 of the patients reported xerostomia and 11 daytime
somnolence as side effects. Neither Salmito et al. nor Domínguez-Durán et al. used the DHI or
HDI to measure outcome, making it more challenging to compare across studies. There are some
known contraindications to use of amitriptyline including: history of significant mental
health problems, pregnancy, cardiac, liver or renal co-morbidities as well as diabetes and
glaucoma. Amitriptyline has also been shown to increase seizure activity in patients with
epilepsy.
1.3 Randomized Controlled Trials Although VM is among the most common causes of dizziness and
is the most common cause of episodic vertigo, the majority of studies investigation outcomes
efficacy are observational in design. These studies typically show improvement for the
intervention, but the inherent bias in that type of investigation is reduced with the use of
randomized controlled trials (RCTs). The process of randomizing allocation of a participant
to an intervention arm should balance observed and unobserved participant characteristics
between groups and allow attribution of any differences in outcome to the study intervention.
Although there are approximately five RCTs comparing various pharmacologic interventions for
VM, there are none including amitriptyline and there are none using lifestyle modification
without pharmacologic intervention.
2.0 Rationale and Specific Aims There is evidence that amitriptyline in isolation and also
our lifestyle modification intervention in isolation can both help reduce symptoms of
dizziness and headache in patients with VM. However, these data are observational and subject
to various types of bias. The purpose of the current investigation is to determine outcomes
from each intervention using randomized allocation of participants diagnosed with definite VM
into either the amitriptyline arm or the lifestyle modification arm. The investigators will
measure for change in dizziness using the DHI and for change in headache using the HDI. For
participants in the lifestyle modification arm, the investigators will also measure for
change in lifestyle factor to determine improvement on those intervention factors. Measures
will be obtained pre-intervention to establish baseline, at 30 days, at 60 days, and at 90
days. The investigators will also re-survey participants one year after initiation of
intervention to determine adherence and status.
The investigators hypothesize that amitriptyline and lifestyle modification intervention will
improve symptoms of dizziness and headache similarly in patients with vestibular migraine
measured at 60 days, but that the improvement will occur sooner (30 days) for participants in
the lifestyle modification arm. Further, the investigators hypothesize there will be fewer
reported side effects from participants in the lifestyle modification arm compared to
participants in the amitriptyline arm.
Although VM is now recognized as a common cause of vertigo, there are few RCTs comparing
efficacy of interventions and there are none comparing lifestyle modification to
amitriptyline. Therefore, the results of the proposed investigation are intended to fill a
critical void in our understanding of management of one of the most common causes of
dizziness.
