Multiple System AtrophyHANCNCT07657520
High-Altitude Neurodegeneration Cohort (HANC) Study
An observational study of Multiple System Atrophy, run by West China Hospital at 1 site in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 40 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple System Atrophy
- How many people
- 0 participants
- Where
- 1 siteChina
- Study dates
- 13 Jun 2026to 30 Jul 2027
- How long will I take part?
- 12 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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).
Read the detailed description
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.
- Conditions
- Multiple System Atrophy
- Being tested
- No Intervention: Observational Cohort
- Keywords
- Chronic Hypoxia, Altitude Sickness
- Medical subject headings
- Multiple System Atrophy, Altitude Sickness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No Intervention: Observational CohortOther
No intervention; observation of altitude exposure and SpO₂ levels
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: No Intervention: Observational Cohort | |
| 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). Receives: Other: No Intervention: Observational Cohort | |
| 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). Receives: Other: No Intervention: Observational Cohort | |
| 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). Receives: Other: No Intervention: Observational Cohort |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Multiple System Atrophy (MSA) at 12 Months
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.
Measured: Baseline to Month 12
Secondary outcomes (3)
Altitude-MSA Association: Hazard Ratio by Altitude Category
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.
Measured: Baseline to Month 12
SpO₂-MSA Association: Hazard Ratio by Nocturnal SpO₂
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.
Measured: Baseline to Month 12
MSA Subtype-Specific Incidence Rates
Incidence rates of MSA-P (parkinsonian subtype) and MSA-C (cerebellar subtype) separately, estimated by clinical phenotype at diagnosis.
Measured: Baseline to Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2026
- Study start13 Jun 2026
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Jul 2027 (estimated)
Why it stopped: Withdrawn due to internal administrative review
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple System AtrophyStudies of the same condition, open and under way.
- More trials run by West China HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Affiliated Hospital of Qinghai University, Tibet Autonomous Region People's Hospital, Kunming Medical University, The First Affiliated Hospital of Guangzhou Medical University, First Affiliated Hospital of Suzhou Medical College, First People's Hospital of Hangzhou, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Guiyang No.1 People's Hospital, Lanzhou University Second Hospital, The First People's Hospital of Yinchuan, Second Affiliated Hospital of Xi'an Jiaotong University, First Affiliated Hospital of Chongqing Medical University, The First People's Hospital of Xining City, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
- Responsible party
- Principal investigator, Zhigang Lan, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07657520
- Sponsor's protocol ID
- WestChinaH-HX-2026-001
- Acronym
- HANC
- Status last verified
- Jun 2026
- First submitted
- 13 Jun 2026
- Last updated
- 25 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-Altitude Neurodegeneration Cohort (HANC) Phase II: A Prospective Multicenter Validation Study on the Association Between Chronic Physiological Hypoxia and Multiple System Atrophy
- ClinicalTrials.gov ID
- NCT07657520
- Acronym / sponsor ID
- HANC / WestChinaH-HX-2026-001
- Conditions
- Multiple System Atrophy
- Keywords
- Chronic Hypoxia, Altitude Sickness
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Withdrawn due to internal administrative review
- Enrolment
- 0 participants (actual)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Collaborators
- Affiliated Hospital of Qinghai University, Tibet Autonomous Region People's Hospital, Kunming Medical University, The First Affiliated Hospital of Guangzhou Medical University, First Affiliated Hospital of Suzhou Medical College, First People's Hospital of Hangzhou, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Guiyang No.1 People's Hospital, Lanzhou University Second Hospital, The First People's Hospital of Yinchuan, Second Affiliated Hospital of Xi'an Jiaotong University, First Affiliated Hospital of Chongqing Medical University, The First People's Hospital of Xining City, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
- Study start
- 13 Jun 2026 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Jul 2027 (estimated)
- First posted
- 18 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 12 Months
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| GROUP_1_Lowland (<500 m) | – | Other: No Intervention: Observational CohortParticipants residing at altitudes below 500 meters. Enrollment sites include Shanghai (4 m), Guangzhou, Suzhou, Hangzhou, Wuhan, Changsha, Nanjing, and Zhengzhou. |
| GROUP_2_Intermediate (500-2,000 m) | – | Other: No Intervention: Observational CohortParticipants 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). |
| GROUP_3_Highland (2,000-3,500 m) | – | Other: No Intervention: Observational CohortParticipants 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). |
| GROUP_4_Extreme Altitude (>3,500 m) | – | Other: No Intervention: Observational CohortParticipants residing at altitudes above 3,500 meters. Enrollment sites include Lhasa (3,656 m), Nagqu (4,500 m), and Ali (4,500 m). |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No Intervention: Observational CohortNo intervention; observation of altitude exposure and SpO₂ levels | Other | GROUP_1_Lowland (<500 m), GROUP_2_Intermediate (500-2,000 m), GROUP_3_Highland (2,000-3,500 m), GROUP_4_Extreme Altitude (>3,500 m) |
Primary outcome
Incidence of Multiple System Atrophy (MSA) at 12 Months
Time frame: 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.
3 secondary outcomes
Altitude-MSA Association: Hazard Ratio by Altitude Category
Time frame: Baseline to Month 12
SpO₂-MSA Association: Hazard Ratio by Nocturnal SpO₂
Time frame: Baseline to Month 12
MSA Subtype-Specific Incidence Rates
Time frame: Baseline to Month 12
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple System Atrophy, run by West China Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Multiple System Atrophy (MSA) at 12 Months (time frame: Baseline to Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2026.