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High-Altitude Neurodegeneration Cohort (HANC) Phase II Study (HANC Phase II)

13 giugno 2026 aggiornato da: Zhigang Lan, West China Hospital

High-Altitude Neurodegeneration Cohort (HANC) Phase II: A Prospective Multicenter Validation Study on the Association Between Chronic Physiological Hypoxia and Multiple System Atrophy

Chronic physiological hypoxia has been implicated in the pathogenesis of multiple system atrophy (MSA), a fatal neurodegenerative disorder of unknown etiology. This prospective, multicenter, observational cohort study (Phase II of the High-Altitude Neurodegeneration Cohort [HANC] study) aims to validate the association between chronic hypoxia exposure and incident MSA risk. A total of 20,000 Han Chinese participants aged 40-75 years will be enrolled from 23 sites across China spanning an altitude gradient from 4 m to 4,500 m. All participants will undergo standardized in-person assessment including questionnaires, physical examination, blood collection, and 3-night consecutive nocturnal pulse oximetry monitoring. Participants are to be followed for incident MSA over 12 months. The primary outcome is newly diagnosed MSA (probable or definite per Gilman consensus criteria), adjudicated by an independent panel of movement disorders specialists. Secondary outcomes include the association between altitude strata and MSA incidence, the association between mean nocturnal SpO₂ and MSA incidence, and incidence rates across MSA subtypes (MSA-P and MSA-C).

Panoramica dello studio

Stato

Attivo, non reclutante

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Osservativo

Iscrizione (Stimato)

20000

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Cina
    • Sichuan
      • Chengdu, Sichuan, Cina
        • West China Hospital of Sichuan University

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

Sì

Metodo di campionamento

Campione non probabilistico

Popolazione di studio

Han Chinese adults aged 40-75 years residing at altitudes ranging from 4 m to 4,500 m across 23 sites in China, with no prior diagnosis of parkinsonism at baseline.

Descrizione

Inclusion Criteria:

  1. Self-identified Han Chinese ethnicity
  2. Age between 40 and 75 years (inclusive)
  3. No prior diagnosis of parkinsonism at baseline
  4. Permanent residence at study site location for ≥1 year prior to enrollment
  5. Ability to provide written informed consent

Exclusion Criteria:

  1. Pre-existing diagnosis of Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, or any other parkinsonian disorder at baseline
  2. Severe chronic pulmonary disease (e.g., COPD GOLD stage ≥3) affecting baseline SpO₂ measurement
  3. Severe cardiovascular disease (e.g., New York Heart Association Class III or IV heart failure)
  4. Cognitive impairment precluding completion of study procedures
  5. Current enrollment in any interventional clinical trial
  6. Life expectancy <12 months due to any medical condition

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

Coorti e interventi

Gruppo / Coorte
Intervento / Trattamento
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.
Altro: No Intervention: Observational Cohort
No intervention; observation of altitude exposure and SpO₂ levels
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).
Altro: No Intervention: Observational Cohort
No intervention; observation of altitude exposure and SpO₂ levels
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).
Altro: No Intervention: Observational Cohort
No intervention; observation of altitude exposure and SpO₂ levels
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).
Altro: No Intervention: Observational Cohort
No intervention; observation of altitude exposure and SpO₂ levels

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Incidence of Multiple System Atrophy (MSA) at 12 Months
Lasso di tempo: Baseline to Month 12
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.
Baseline to Month 12

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Altitude-MSA Association: Hazard Ratio by Altitude Category
Lasso di tempo: Baseline to Month 12
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.
Baseline to Month 12
SpO₂-MSA Association: Hazard Ratio by Nocturnal SpO₂
Lasso di tempo: Baseline to Month 12
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.
Baseline to Month 12
MSA Subtype-Specific Incidence Rates
Lasso di tempo: Baseline to Month 12
Incidence rates of MSA-P (parkinsonian subtype) and MSA-C (cerebellar subtype) separately, estimated by clinical phenotype at diagnosis.
Baseline to Month 12

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

West China Hospital

Collaboratori

First People's Hospital of Hangzhou
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
The First Affiliated Hospital of Guangzhou Medical University
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Second Affiliated Hospital of Xi'an Jiaotong University
First Affiliated Hospital of Chongqing Medical University
Affiliated Hospital of Qinghai University
Tibet Autonomous Region People's Hospital
First Affiliated Hospital of Suzhou Medical College
Kunming Medical University
Lanzhou University Second Hospital
The First People's Hospital of Yinchuan
Guiyang No.1 People's Hospital
The First People's Hospital of Xining City

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

13 giugno 2026

Completamento primario (Stimato)

30 luglio 2027

Completamento dello studio (Stimato)

30 luglio 2027

Date di iscrizione allo studio

Primo inviato

13 giugno 2026

Primo inviato che soddisfa i criteri di controllo qualità

13 giugno 2026

Primo Inserito (Effettivo)

18 giugno 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

18 giugno 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

13 giugno 2026

Ultimo verificato

1 giugno 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • WestChinaH-HX-2026-001

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Periodo di condivisione IPD

Data will be available beginning 12 months after study completion.

Criteri di accesso alla condivisione IPD

Requests should be directed to the corresponding author; a signed data access agreement will be required.

Tipo di informazioni di supporto alla condivisione IPD

  • STUDIO_PROTOCOLLO
  • LINFA

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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Prove cliniche su No Intervention: Observational Cohort

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Sponsor e collaboratori

Condizioni mediche

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CROs by country

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Condizioni

Malattie rare

Interventi farmacologici

Supplementi dietetici

Sponsor / Collaboratori

Sedi

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