Comparing Migraine Preventive Therapies vs. Anti-CGRP Therapies for Tinnitus in Patients With Migraine (COMPACT-PM) (COMPACT-PM)
Comparative Outcomes of Migraine Preventives and Anti-CGRP Therapies for Tinnitus in Patients With Migraine: A Randomized Active-Comparator Controlled Trial (COMPACT-PM)
調査の概要
状態
詳細な説明
Tinnitus affects approximately 15% of the global population, and migraine history is an established risk factor for both its prevalence and severity. Converging preclinical and clinical evidence implicates calcitonin gene-related peptide (CGRP) signaling at the intersection of these two conditions: CGRP and its receptors are expressed in cochlear inner and outer hair cells, the spiral ganglion, and the vestibular end organs; in a chronic migraine mouse model, cochlear CGRP expression is upregulated and CGRP administration attenuates cochlear deficits; and in humans, conventional migraine preventive medications have been shown to reduce tinnitus burden as measured by the TFI. Whether CGRP-targeting agents confer additional or differential benefit for tinnitus - given their direct cochlear and vestibular targets - has not been evaluated in a randomized controlled trial.
COMPACT-PM addresses this gap using a randomized, open-label, active-comparator controlled design. A placebo arm is not included because withholding migraine preventive treatment from patients with a clinical indication for preventive therapy would be ethically inappropriate; both arms therefore receive active, clinically indicated migraine treatment, and randomization controls for treatment selection bias. Within each arm, the specific agent is selected by the treating clinician based on clinical appropriateness, patient factors, and insurance coverage; participants must have confirmed insurance access to at least one CGRP-targeting agent prior to randomization.
研究の種類
入学 (推定)
段階
- フェーズ 4
連絡先と場所
研究連絡先
- 名前:Jwala P Rejimon, AuD
- 電話番号:650-736-2354
- メール:jrejimon@stanford.edu
研究連絡先のバックアップ
- 名前:Research Coordinator
- メール:traneric@stanford.edu
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Age 18 years or older
- Non-pulsatile, subjective tinnitus present for at least 6 months
- Tinnitus Functional Index (TFI) score greater than 25 at screening, indicating at least mild-to-moderate tinnitus burden
- Current or past history of migraine, vestibular migraine, or episodic headache disorder, diagnosed by a physician or meeting ICHD-3 criteria
- Clinically appropriate candidate for migraine preventive therapy as determined by the treating clinician
- Stable medication regimen for at least 3 months prior to enrollment (no new medications started or stopped within 3 months of screening)
- Ability to provide written informed consent
- Ability to complete self-report questionnaires in English or with certified interpreter assistance
- Willingness to attend three in-person study visits over 24 weeks and complete daily symptom diaries
Exclusion Criteria:
- Pulsatile tinnitus or objective tinnitus (tinnitus audible to examiner)
- Pregnancy, planned pregnancy during the study period, or breastfeeding
- Participation in any other interventional tinnitus treatment research protocol during the study period
- Currently receiving a CGRP-targeting medication (for participants being considered for the conventional arm) or a conventional migraine preventive medication listed in this protocol (for participants being considered for the CGRP arm) - to avoid within-arm ineligibility at randomization
- Known contraindication to all medications within the assigned study arm
- History of serious cardiovascular event (myocardial infarction, stroke, or unstable angina) within 6 months of enrollment
- Severe hepatic or renal impairment that would contraindicate study medications
- Active psychiatric disorder requiring medication adjustment within 3 months of enrollment
- Known hypersensitivity or prior serious adverse reaction to a medication within the assigned study arm
- Active malignancy or life expectancy less than 12 months
- Inability to complete study procedures or follow-up visits in the judgment of the investigator
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的:CGRP-Targeting Therapy
Participants assigned to this arm receive one CGRP-targeting migraine preventive agent selected by the treating clinician based on clinical appropriateness and patient factors.
Options include anti-CGRP monoclonal antibodies (galcanezumab, erenumab, fremanezumab, eptinezumab) or gepants (atogepant, rimegepant).
Treatment duration is 24 weeks.
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240 mg loading dose, then 120 mg monthly; intramuscular injection.
Manufacturer: Eli Lilly.
70-140 mg monthly; subcutaneous injection.
Manufacturer: Amgen/Novartis.
100-300 mg every 3 months; intravenous infusion.
Manufacturer: Lundbeck.
10, 30, or 60 mg daily; oral.
Manufacturer: AbbVie.
|
|
アクティブコンパレータ:Conventional Migraine Preventive Therapy
Participants assigned to this arm receive one conventional migraine preventive agent selected by the treating clinician based on clinical appropriateness and patient factors.
Options are organized by class: antidepressants (amitriptyline, nortriptyline, venlafaxine), antihypertensives (propranolol, verapamil, candesartan), or anticonvulsants (topiramate).
Treatment duration is 24 weeks.
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10-100 mg daily; oral.
Generic.
10-100 mg daily; oral.
Generic.
10-120 mg daily; oral.
Generic.
120-480 mg SR daily; oral.
Generic.
2-32 mg daily; oral. Generic.
12.5-200 mg daily; oral.
Generic.
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in Tinnitus Functional Index (TFI) Score
時間枠:Baseline to 24 weeks
|
The TFI is a validated 25-item self-report questionnaire measuring the negative impact of tinnitus on daily life.
Scores range from 0-100; higher scores indicate greater tinnitus burden.
The minimally important clinical difference is 13 points.
The primary endpoint is the between-arm difference in TFI change from baseline to 24 weeks.
The Tinnitus Functional Index (TFI) is a validated 25-item self-report questionnaire measuring the negative impact of tinnitus on daily life.
Scores range from 0-100; higher scores indicate greater tinnitus burden.
The minimally important clinical difference is 13 points.
The primary endpoint is the between-arm difference in TFI change from baseline to 24 weeks, with a greater reduction indicating better outcome.
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Baseline to 24 weeks
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in Tinnitus Functional Index (TFI) Score at 12 Weeks
時間枠:Baseline to 12 weeks
|
Between-arm difference in TFI change from baseline to 12 weeks, to characterize early treatment response.
The Tinnitus Functional Index (TFI) is a validated 25-item self-report questionnaire measuring the negative impact of tinnitus on daily life.
Scores range from 0-100; higher scores indicate greater tinnitus burden.
The minimally important clinical difference is 13 points.
The primary endpoint is the between-arm difference in TFI change from baseline to 24 weeks, with a greater reduction indicating better outcome.
|
Baseline to 12 weeks
|
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TFI Score Trajectory
時間枠:Weeks 4, 8, 16, 20
|
Within- and between-arm TFI change at weeks 4, 8, 16, and 20 to characterize the time course of tinnitus response.
The Tinnitus Functional Index (TFI) is a validated 25-item self-report questionnaire measuring the negative impact of tinnitus on daily life.
Scores range from 0-100; higher scores indicate greater tinnitus burden.
The minimally important clinical difference is 13 points.
The primary endpoint is the between-arm difference in TFI change from baseline to 24 weeks, with a greater reduction indicating better outcome.
|
Weeks 4, 8, 16, 20
|
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Change in Tinnitus Handicap Inventory (THI) Score
時間枠:Baseline, 12 weeks, 24 weeks
|
The THI is a validated 25-item questionnaire measuring tinnitus-related handicap across functional, emotional, and catastrophic subscales.
Scores range from 0-100.
The Tinnitus Handicap Inventory (THI) is a validated 25-item questionnaire measuring tinnitus-related handicap across functional, emotional, and catastrophic subscales.
Scores range from 0-100; higher scores indicate greater handicap and worse outcome.
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Baseline, 12 weeks, 24 weeks
|
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Change in Visual Analog Scale (VAS) Tinnitus Loudness
時間枠:Baseline, 12 weeks, 24 weeks
|
Participant-rated tinnitus loudness on a 0-10 VAS, where 0 = no loudness and 10 = worst imaginable loudness.
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Baseline, 12 weeks, 24 weeks
|
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Change in Visual Analog Scale (VAS) Tinnitus Unpleasantness
時間枠:Baseline, 12 weeks, 24 weeks
|
Participant-rated tinnitus unpleasantness on a 0-10 VAS, where 0 = not unpleasant and 10 = worst imaginable unpleasantness.
|
Baseline, 12 weeks, 24 weeks
|
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Patient Global Impression of Change (PGIC)
時間枠:12 weeks, 24 weeks
|
Single-item participant-rated global impression of change in tinnitus since starting study treatment, rated on a 7-point scale from 1 (very much worse) to 7 (very much improved).
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12 weeks, 24 weeks
|
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Change in Headache Impact Test-6 (HIT-6) Score
時間枠:Baseline, 12 weeks, 24 weeks
|
The HIT-6 is a validated 6-item questionnaire measuring the impact of headaches on daily functioning.
Scores range from 36-78; higher scores indicate greater headache impact.
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Baseline, 12 weeks, 24 weeks
|
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Change in Migraine Disability Assessment (MIDAS) Score
時間枠:Baseline, 12 weeks, 24 weeks
|
The Migraine Disability Assessment (MIDAS) quantifies headache-related disability over the prior 3 months based on lost productive time, scored in days.
Scores range from 0 to unlimited; higher scores indicate greater disability and worse outcome.
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Baseline, 12 weeks, 24 weeks
|
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Change in Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI) Score
時間枠:Baseline, 12 weeks, 24 weeks
|
The Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI) is a validated 25-item patient-reported outcome measure specific to vestibular migraine, assessing symptom frequency, severity, and impact.
Scores range from 0-100; higher scores indicate greater disease burden and worse outcome.
Administered to all participants; subgroup analysis planned for those with confirmed vestibular migraine diagnosis.
|
Baseline, 12 weeks, 24 weeks
|
|
Change in Dizziness Handicap Inventory (DHI) Score
時間枠:Baseline, 12 weeks, 24 weeks
|
The Dizziness Handicap Inventory (DHI) is a validated 25-item questionnaire measuring the self-perceived handicap imposed by dizziness and unsteadiness.
Scores range from 0-100; higher scores indicate greater handicap and worse outcome.
|
Baseline, 12 weeks, 24 weeks
|
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Monthly Headache Days
時間枠:Baseline through 24 weeks
|
Number of headache days per month recorded in participant daily diary, averaged over each 4-week interval between study visits.
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Baseline through 24 weeks
|
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Monthly Dizzy Days
時間枠:Baseline through 24 weeks
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Number of days with dizziness or vertigo per month recorded in participant daily diary, averaged over each 4-week interval between study visits.
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Baseline through 24 weeks
|
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Monthly Nausea Days
時間枠:Baseline through 24 weeks
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Number of days with nausea per month recorded in participant daily diary, averaged over each 4-week interval between study visits.
|
Baseline through 24 weeks
|
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Acute Medication Use
時間枠:Baseline through 24 weeks
|
Number of days per month with acute migraine or vestibular rescue medication use, recorded in participant daily diary.
|
Baseline through 24 weeks
|
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Change in Pure Tone Audiometric Thresholds
時間枠:Baseline, 12 weeks, 24 weeks
|
Change in air conduction pure tone thresholds at 250-8000 Hz from baseline, assessed by standard audiogram.
|
Baseline, 12 weeks, 24 weeks
|
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Change in Speech-in-Noise Performance (QuickSIN)
時間枠:Baseline, 12 weeks, 24 weeks
|
Change in signal-to-noise ratio loss from baseline as measured by the Quick Speech-in-Noise (QuickSIN) test, reflecting auditory processing in noise.
|
Baseline, 12 weeks, 24 weeks
|
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Change in Auditory Brainstem Response (ABR)
時間枠:Baseline, 12 weeks, 24 weeks
|
Change in ABR wave latencies and amplitudes from baseline, reflecting peripheral and central auditory pathway integrity.
|
Baseline, 12 weeks, 24 weeks
|
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Change in Tinnitus Pitch and Loudness Characteristics
時間枠:Baseline, 12 weeks, 24 weeks
|
Change in psychoacoustic tinnitus pitch match (Hz) and loudness match (dB SL) from baseline.
|
Baseline, 12 weeks, 24 weeks
|
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Change in Video Head Impulse Test (vHIT)
時間枠:Baseline, 12 weeks, 24 weeks
|
Change in semicircular canal vestibulo-ocular reflex (VOR) gain and saccades from baseline, assessed by vHIT across all six semicircular canals.
|
Baseline, 12 weeks, 24 weeks
|
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Rotary Chair - VOR Gain
時間枠:Baseline, 12 weeks, 24 weeks
|
Change in vestibulo-ocular reflex (VOR) gain from baseline, assessed by sinusoidal harmonic acceleration rotary chair testing across multiple frequencies.
Gain is a unitless ratio (eye velocity / chair velocity); values closer to 1.0 indicate better vestibular function.
|
Baseline, 12 weeks, 24 weeks
|
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Change in Cervical and Ocular Vestibular Evoked Myogenic Potentials (cVEMP/oVEMP)
時間枠:Baseline, 12 weeks, 24 weeks
|
Change in cVEMP and oVEMP amplitude, threshold, and latency from baseline, reflecting saccular, utricular, and inferior/superior vestibular nerve function.
|
Baseline, 12 weeks, 24 weeks
|
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VNG - Ocular Motor Testing
時間枠:Baseline, 12 weeks, 24 weeks
|
Change in ocular motor parameters from baseline assessed by videonystagmography (VNG), including gaze stability, saccade accuracy and latency, smooth pursuit gain, and optokinetic response gain.
Each parameter is reported in its respective unit (degrees/second, milliseconds, or unitless ratio); values will be analyzed individually.
|
Baseline, 12 weeks, 24 weeks
|
|
Adverse Event Rate
時間枠:Baseline through 24 weeks plus 30-day safety follow-up
|
Frequency and severity of adverse events and serious adverse events in each arm, assessed throughout the study period and graded by CTCAE criteria.
|
Baseline through 24 weeks plus 30-day safety follow-up
|
|
TFI Responder Rate
時間枠:24 weeks
|
Proportion of participants in each arm achieving a clinically meaningful reduction of 13 or more points from baseline on the Tinnitus Functional Index (TFI) at 24 weeks, representing the minimum important clinical difference established by Meikle et al. (2012).
|
24 weeks
|
|
Rotary Chair - VOR Phase
時間枠:Time Frame: Baseline, 12 weeks, 24 weeks
|
Change in vestibulo-ocular reflex (VOR) phase lead from baseline, assessed by sinusoidal harmonic acceleration rotary chair testing.
Phase is reported in degrees; lower phase lead at low frequencies indicates better vestibular compensation.
|
Time Frame: Baseline, 12 weeks, 24 weeks
|
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Rotary Chair - VOR Symmetry
時間枠:Time Frame: Baseline, 12 weeks, 24 weeks
|
Change in vestibulo-ocular reflex (VOR) directional preponderance/symmetry from baseline, assessed by sinusoidal harmonic acceleration rotary chair testing.
Symmetry is reported as a percentage asymmetry; values closer to 0% indicate better symmetry.
|
Time Frame: Baseline, 12 weeks, 24 weeks
|
|
VNG - Positional and Positioning Nystagmus
時間枠:Time Frame: Baseline, 12 weeks, 24 weeks
|
Change in nystagmus slow-phase velocity (SPV) from baseline during positional and positioning maneuvers assessed by videonystagmography (VNG).
SPV is reported in degrees/second; lower values indicate less nystagmus.
|
Time Frame: Baseline, 12 weeks, 24 weeks
|
|
VNG - Caloric Testing
時間枠:Time Frame: Baseline, 12 weeks, 24 weeks
|
Change in unilateral weakness and directional preponderance from baseline assessed by caloric irrigation during videonystagmography (VNG).
Unilateral weakness and directional preponderance are reported as percentages; values closer to 0% indicate better symmetry.
|
Time Frame: Baseline, 12 weeks, 24 weeks
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in Hyperacusis Questionnaire (HQ) Score
時間枠:Baseline, 12 weeks, 24 weeks
|
The Hyperacusis Questionnaire (HQ) is a 14-item questionnaire measuring hyperacusis severity and impact.
Scores range from 0-42; higher scores indicate greater hyperacusis severity and worse outcome.
Included as an exploratory outcome given the frequent co-occurrence of hyperacusis and tinnitus in this population.
|
Baseline, 12 weeks, 24 weeks
|
|
Pupillometry Changes
時間枠:Baseline, 12 weeks, 24 weeks
|
Change in sound-evoked pupil dilation amplitude and latency from baseline, as a measure of olivocochlear and autonomic auditory pathway function. Change in resting pupil diameter from baseline as a measure of baseline autonomic tone. Exploratory mechanistic outcome. |
Baseline, 12 weeks, 24 weeks
|
協力者と研究者
スポンサー
捜査官
- 主任研究者:Kristen K. Steenerson、Stanford University
- 主任研究者:Matthew Fitzgerald、Stanford University
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
- 神経症状
- 脳疾患
- 中枢神経系疾患
- 神経系疾患
- 頭痛障害、一次性
- 頭痛の病気
- 耳鼻咽喉科疾患
- 感覚障害
- 耳の病気
- 聴覚障害
- 病理学的状態、徴候および症状
- 徴候と症状
- 片頭痛
- 耳鳴り
- 有機化学物質
- 炭化水素
- 炭化水素、周期的
- 炭水化物
- ナフタレン
- 多環芳香族炭化水素
- 炭化水素、芳香
- 多環式化合物
- アミン
- アルコール
- フェノキシプロパノラミン
- プロパノラミン
- アミノアルコール
- プロパノール
- フェネチルアミン
- エチルアミン
- 砂糖
- ジベンゾシクロヘプテン
- ベンゾシクロヘペテン
- 六角形
- 単糖
- フルクトース
- ケトス
- トピラマート
- ベラパミル
- プロプラノロール
- アミトリプチリン
- ノルトリプチリン
- eptinezumab
- atogepant
- エレヌマブ
- ガルカネズマブ
- カンデサルタン
その他の研究ID番号
- IRB Protocol #86437
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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