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

22 août 2026 mis à jour par: 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).

Aperçu de l'étude

Statut

Retiré

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Observationnel

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Oui

Méthode d'échantillonnage

Échantillon non probabiliste

Population étudiée

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.

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

Cohortes et interventions

Groupe / Cohorte
Intervention / Traitement
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.
Autre: 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).
Autre: 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).
Autre: 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).
Autre: No Intervention: Observational Cohort
No intervention; observation of altitude exposure and SpO₂ levels

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Incidence of Multiple System Atrophy (MSA) at 12 Months
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Altitude-MSA Association: Hazard Ratio by Altitude Category
Délai: 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
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

West China Hospital

Collaborateurs

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

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

13 juin 2026

Achèvement primaire (Estimé)

30 juillet 2027

Achèvement de l'étude (Estimé)

30 juillet 2027

Dates d'inscription aux études

Première soumission

13 juin 2026

Première soumission répondant aux critères de contrôle qualité

13 juin 2026

Première publication (Réel)

18 juin 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

25 août 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

22 août 2026

Dernière vérification

1 juin 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • WestChinaH-HX-2026-001

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Délai de partage IPD

Data will be available beginning 12 months after study completion.

Critères d'accès au partage IPD

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

Type d'informations de prise en charge du partage d'IPD

  • PROTOCOLE D'ÉTUDE
  • SÈVE

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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