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
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Anslået)
Kontakter og lokationer
Studiesteder
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Sichuan
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Chengdu, Sichuan, Kina
- West China Hospital of Sichuan University
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Prøveudtagningsmetode
Studiebefolkning
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
Intervention / Behandling |
|---|---|
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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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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Incidence of Multiple System Atrophy (MSA) at 12 Months
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Altitude-MSA Association: Hazard Ratio by Altitude Category
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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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Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- WestChinaH-HX-2026-001
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-delingstidsramme
IPD-delingsadgangskriterier
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- SAP
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