## Protocol Section
### Identification Module
**NCT ID:** NCT06417684

**Acronym:** RCTVM

**Brief Title:** Comparison of Amitriptyline to Lifestyle Modification as Intervention for Vestibular Migraine

**Official Title:** Comparison of Amitriptyline to Lifestyle Modification as Intervention for Vestibular Migraine

#### Organization Study ID Info
**ID:** 240605
#### Organization
**Class:** OTHER
**Full Name:** Vanderbilt University Medical Center
### Status Module
#### Completion Date
**Date:** 2026-06

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-11

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-06

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-11
**Study First Submit QC Date:** 2024-05-11
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Vanderbilt University Medical Center

#### Responsible Party

**Investigator Affiliation:** Vanderbilt University Medical Center

**Investigator Full Name:** Richard A. Roberts, Ph.D.

**Investigator Title:** Associate Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** True

**Oversight Has DMC:** False

### Description Module

**Brief 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. We 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, we 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. We will also re-survey participants one year after initiation of intervention to determine adherence and status.

**Detailed 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, we 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, we decrease the symptoms of dizziness and headache. In our studies, we measure outcomes with two validated instruments, the dizziness handicap inventory (DHI) and the headache disability index (HDI). Using this approach, we have found significant improvement within two weeks of starting the lifestyle modification intervention. Further, we 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. We 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). We 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. We 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. We will measure for change in dizziness using the DHI and for change in headache using the HDI. For participants in the lifestyle modification arm, we 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. We will also re-survey participants one year after initiation of intervention to determine adherence and status.

We 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, we 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.

### Conditions Module

**Conditions:**

- Vestibular Migraine

**Keywords:**

- vestibular

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 100

**Type:** ESTIMATED

**Phases:**

- EARLY_PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** amitriptyline, tablet, 25 mg, once daily, 90 days

**Intervention Names:**

- Drug: Amitriptyline

**Label:** Amitriptyline

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Written and video instructions to help improve restful sleep, mealtime regularity, avoidance of dietary triggers, and exercise for 90 days.

**Intervention Names:**

- Drug: Amitriptyline

**Label:** Lifestyle Modification

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Amitriptyline

- Lifestyle Modification

**Description:** 25 mg prescribed to be taken once daily for 90 days each evening.

**Name:** Amitriptyline

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** We will measure for reduction of dizziness using the Dizziness Handicap Inventory (DHI)

**Measure:** Reduction of Dizziness

**Time Frame:** Baseline DHI pre-intervention, 30, 60, 90 days and 1 year.

**Description:** We will measure for reduction of dizziness using the Headache Disability Inventory Inventory (HDI)

**Measure:** Reduction of Headache

**Time Frame:** Baseline HDI pre-intervention, 30, 60, 90 days and 1 year.

**Description:** Participants will report any side effects

**Measure:** Side Effects

**Time Frame:** 30, 60, 90 days and 1 year

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* English-speaking adults
* Diagnosed with Definite Vestibular Migraine
* Currently prescribed rescue medication for migraine is acceptable

Exclusion Criteria:

* Non-English speaking
* Diagnosed and undergoing treatment for active Definite Meniere's disease
* Already using amitriptyline
* Contraindicated for intervention with amitriptyline including:

Patients with Hepatic Impairment, Patients with Renal Impairment, Pregnancy, Breastfeeding, Elderly Patients, Allergy to amitriptyline, Heart attack, Used an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazide, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others, Used an "SSRI" antidepressant in the past 5 weeks, such as citalopram, escitalopram, fluoxetine (Prozac), fluvoxamine, paroxetine, sertraline (Zoloft), trazodone, or vilazodone, Bipolar disorder (manic-depression) or schizophrenia, Mental illness or psychosis; Stroke, Seizures, Diabetes (amitriptyline may raise or lower blood sugar); Glaucoma, Problems with urination

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** richard.a.roberts@vumc.org

**Name:** Richard A Roberts, PhD

**Phone:** 615-322-7384

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Nashville

**Contacts:**

***Contact 1:***

- **Email:** richard.a.roberts@vumc.org

- **Name:** Richard A Roberts, Ph.D.

- **Phone:** 615-322-7384

- **Role:** CONTACT

**Country:** United States

**Facility:** Vanderbilt University Medical Center

**State:** Tennessee

**Zip:** 37232

#### Overall Officials

**Official 1:**

**Affiliation:** Vanderbilt University Medical Center

**Name:** Richard A Roberts, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000051270

- Term: Headache Disorders, Primary

- ID: D000020773

- Term: Headache Disorders

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M11852

- Name: Migraine Disorders

- Relevance: HIGH

- As Found: Migraine

- ID: M9351

- Name: Headache

- Relevance: LOW

- As Found: Unknown

- ID: M22529

- Name: Headache Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M26657

- Name: Headache Disorders, Primary

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008881

- Term: Migraine Disorders

### Intervention Browse Module - Ancestors

- ID: D000000929

- Term: Antidepressive Agents, Tricyclic

- ID: D000000928

- Term: Antidepressive Agents

- ID: D000011619

- Term: Psychotropic Drugs

- ID: D000018712

- Term: Analgesics, Non-Narcotic

- ID: D000000700

- Term: Analgesics

- ID: D000018689

- Term: Sensory System Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018759

- Term: Adrenergic Uptake Inhibitors

- ID: D000014179

- Term: Neurotransmitter Uptake Inhibitors

- ID: D000049990

- Term: Membrane Transport Modulators

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000018663

- Term: Adrenergic Agents

- ID: D000018377

- Term: Neurotransmitter Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Analg

- Name: Analgesics

- Abbrev: PsychDr

- Name: Psychotropic Drugs

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M3977

- Name: Amitriptyline

- Relevance: HIGH

- As Found: FLT

- ID: M4247

- Name: Antidepressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4248

- Name: Antidepressive Agents, Tricyclic

- Relevance: LOW

- As Found: Unknown

- ID: M14474

- Name: Psychotropic Drugs

- Relevance: LOW

- As Found: Unknown

- ID: M4032

- Name: Analgesics

- Relevance: LOW

- As Found: Unknown

- ID: M20786

- Name: Analgesics, Non-Narcotic

- Relevance: LOW

- As Found: Unknown

- ID: M20746

- Name: Adrenergic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20504

- Name: Neurotransmitter Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000000639

- Term: Amitriptyline

### Misc Info Module

- Version Holder: 2024-05-31
