High-Altitude Neurodegeneration Cohort (HANC) Phase II Study (HANC Phase II)
13 de junio de 2026 actualizado por: 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).
Descripción general del estudio
Estado
Activo, no reclutando
Condiciones
Intervención / Tratamiento
Descripción detallada
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 de estudio
De observación
Inscripción (Estimado)
20000
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
-
-
Sichuan
-
Chengdu, Sichuan, Porcelana
- West China Hospital of Sichuan University
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Sí
Método de muestreo
Muestra no probabilística
Población de estudio
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.
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
|---|---|
|
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.
|
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).
|
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).
|
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).
|
No intervention; observation of altitude exposure and SpO₂ levels
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Incidence of Multiple System Atrophy (MSA) at 12 Months
Periodo de tiempo: 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
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Altitude-MSA Association: Hazard Ratio by Altitude Category
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
13 de junio de 2026
Finalización primaria (Estimado)
30 de julio de 2027
Finalización del estudio (Estimado)
30 de julio de 2027
Fechas de registro del estudio
Enviado por primera vez
13 de junio de 2026
Primero enviado que cumplió con los criterios de control de calidad
13 de junio de 2026
Publicado por primera vez (Actual)
18 de junio de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
18 de junio de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
13 de junio de 2026
Última verificación
1 de junio de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Sinucleinopatías
- Enfermedades Cerebrales
- Enfermedades del Sistema Nervioso Central
- Enfermedades del Sistema Nervioso
- Enfermedades de las vías respiratorias
- Trastornos de la respiración
- Enfermedades neurodegenerativas
- Trastornos del movimiento
- Enfermedades de los ganglios basales
- Disautonomías primarias
- Enfermedades del sistema nervioso autónomo
- Atrofia multisistémica
- Vertigo
Otros números de identificación del estudio
- WestChinaH-HX-2026-001
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
SÍ
Marco de tiempo para compartir IPD
Data will be available beginning 12 months after study completion.
Criterios de acceso compartido de IPD
Requests should be directed to the corresponding author; a signed data access agreement will be required.
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
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