High-Altitude Neurodegeneration Cohort (HANC) Phase II Study (HANC Phase II)
High-Altitude Neurodegeneration Cohort (HANC) Phase II: A Prospective Multicenter Validation Study on the Association Between Chronic Physiological Hypoxia and Multiple System Atrophy
調査の概要
詳細な説明
Background: Multiple system atrophy (MSA) is a rapidly progressive synucleinopathy characterized by glial cytoplasmic inclusions in oligodendrocytes. Although most cases are considered sporadic, an environmental trigger has not been established. Epidemiological observations have reported disproportionately high MSA prevalence at high altitudes, but these have been dismissed as ascertainment bias. Chronic hypoxia stabilizes hypoxia-inducible factors (HIFs), which regulate mitochondrial gene expression and oxidative stress pathways.
Hypothesis: Chronic physiological hypoxia is an independent causal risk factor for MSA, operating through a HIF-1α-dependent mitochondrial lipid peroxidation cascade.
Study Design: Phase II is a prospective validation cohort designed to replicate findings from the retrospective Phase I (N=284,756). Unlike the retrospective Phase I which relied on healthcare claims data, Phase II collects primary data prospectively using standardized protocols.
Altitude Strata: Participants were enrolled from four altitude categories: (1) Lowland: <500 m (8 sites); (2) Intermediate: 500-2,000 m (7 sites); (3) Highland: 2,000-3,500 m (5 sites); (4) Extreme altitude: >3,500 m (3 sites).
Exposure Assessment: Residential altitude was verified through national identity registry cross-linkage. Nocturnal peripheral oxygen saturation (SpO₂) was measured using Nonin WristOx2 devices sampled at 1 Hz for three consecutive nights.
Outcome Adjudication: All potential MSA cases identified during follow-up will be adjudicated by a panel of five board-certified movement disorders specialists using the Gilman second consensus criteria. Adjudication will be supplemented by brain MRI review and video examination where available. Only probable and definite MSA cases are included in primary analyses.
Statistical Analysis: Cox proportional hazards models will be used to estimate hazard ratios for MSA incidence by altitude category and SpO₂ quartiles, adjusting for age, sex, smoking, pesticide exposure, family history, SNCA genotype, BMI, and occupational solvent exposure. Kaplan-Meier survival curves will compare MSA-free survival across altitude strata.
研究の種類
入学 (推定)
連絡先と場所
研究場所
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Sichuan
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Chengdu、Sichuan、中国
- West China Hospital of Sichuan University
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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
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- Self-identified Han Chinese ethnicity
- Age between 40 and 75 years (inclusive)
- No prior diagnosis of parkinsonism at baseline
- Permanent residence at study site location for ≥1 year prior to enrollment
- Ability to provide written informed consent
Exclusion Criteria:
- Pre-existing diagnosis of Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, or any other parkinsonian disorder at baseline
- Severe chronic pulmonary disease (e.g., COPD GOLD stage ≥3) affecting baseline SpO₂ measurement
- Severe cardiovascular disease (e.g., New York Heart Association Class III or IV heart failure)
- Cognitive impairment precluding completion of study procedures
- Current enrollment in any interventional clinical trial
- Life expectancy <12 months due to any medical condition
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
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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GROUP_1_Lowland (<500 m)
Participants residing at altitudes below 500 meters.
Enrollment sites include Shanghai (4 m), Guangzhou, Suzhou, Hangzhou, Wuhan, Changsha, Nanjing, and Zhengzhou.
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No intervention; observation of altitude exposure and SpO₂ levels
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GROUP_2_Intermediate (500-2,000 m)
Participants residing at altitudes between 500 and 2,000 meters.
Enrollment sites include Kunming (1,890 m), Guiyang (1,100 m), Lanzhou (1,520 m), Yinchuan (1,100 m), Xi'an (400 m - borderline, verify), Chengdu (500 m), and Chongqing (240 m).
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No intervention; observation of altitude exposure and SpO₂ levels
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GROUP_3_Highland (2,000-3,500 m)
Participants residing at altitudes between 2,000 and 3,500 meters.
Enrollment sites include Xining (2,295 m), Golog (3,700 m - verify), Haixi (2,980 m), Yushu (3,700 m), and Ganzi (3,400 m).
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No intervention; observation of altitude exposure and SpO₂ levels
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GROUP_4_Extreme Altitude (>3,500 m)
Participants residing at altitudes above 3,500 meters.
Enrollment sites include Lhasa (3,656 m), Nagqu (4,500 m), and Ali (4,500 m).
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No intervention; observation of altitude exposure and SpO₂ levels
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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 |
|---|---|---|
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Incidence of Multiple System Atrophy (MSA) at 12 Months
時間枠：Baseline to Month 12
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Number of participants with newly diagnosed probable or definite MSA during the 12-month follow-up period.
Diagnosis is based on Gilman second consensus criteria and adjudicated by an independent panel of five movement disorders specialists.
Adjudication includes brain MRI review and video examination where available.
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Baseline to Month 12
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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 |
|---|---|---|
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Altitude-MSA Association: Hazard Ratio by Altitude Category
時間枠：Baseline to Month 12
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Association between residential altitude category (4 strata: <500 m, 500-2,000 m, 2,000-3,500 m, >3,500 m) and MSA incidence, estimated using multivariable Cox proportional hazards models adjusted for age, sex, smoking, pesticide exposure, family history, SNCA genotype, BMI, and occupational solvent exposure.
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Baseline to Month 12
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SpO₂-MSA Association: Hazard Ratio by Nocturnal SpO₂
時間枠：Baseline to Month 12
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Association between mean nocturnal peripheral oxygen saturation (SpO₂) quartiles (<88%, 88-91%, 92-94%, >94%) and MSA incidence, estimated using multivariable Cox proportional hazards models with the same covariate adjustment set as the primary analysis.
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Baseline to Month 12
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MSA Subtype-Specific Incidence Rates
時間枠：Baseline to Month 12
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Incidence rates of MSA-P (parkinsonian subtype) and MSA-C (cerebellar subtype) separately, estimated by clinical phenotype at diagnosis.
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Baseline to Month 12
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協力者と研究者
スポンサー
協力者
研究記録日
主要日程の研究
研究開始 (実際)
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
その他の研究ID番号
- WestChinaH-HX-2026-001
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?
IPD 共有時間枠
IPD 共有アクセス基準
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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No Intervention: Observational Cohortの臨床試験
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