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NCT Number: NCT07036939

Efficacy and Safety of Bilateral Cervical Lymphatic-Venous Anastomosis in the Treatment of Multiple System Atrophy

Multiple System Atrophy (MSA) is a rare and aggressive neurodegenerative disorder characterized by a combination of motor impairments, autonomic dysfunction, and cerebellar ataxia, with no currently available disease-modifying therapies. Emerging evidence suggests that impaired glymphatic clearance of pathological α-synuclein aggregates may contribute to disease progression. This clinical study investigates the potential of bilateral cervical lymphatic-venous anastomosis (LVA) - a microsurgical procedure connecting deep cervical lymphatics to veins - to enhance glymphatic drainage and slow disease progression in MSA patients.

This single-center prospective clinical study will enroll patients with clinically confirmed MSA to undergo bilateral cervical lymphatic-venous anastomosis (LVA). Through comprehensive pre- and postoperative evaluations including clinical scale assessments, blood biomarker testing, and neuroimaging examinations, the study aims to evaluate the short-term and long-term effects of bilateral LVA on patients' motor function, autonomic symptoms, and quality of life, as well as its potential to delay disease progression.

The study will further investigate whether the potential clinical improvements from LVA are mediated through enhanced intracranial lymphatic drainage function and subsequent clearance of pathological α-Syn protein in the brain. Safety assessments will include monitoring and recording both short-term and long-term postoperative complications. This research may provide a novel non-pharmacological intervention approach for MSA treatment.

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Key information

Conditions

Multiple System Atrophy Autonomic Nervous System Diseases Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Movement Disorders Nervous System Diseases Neurodegenerative Diseases Primary Dysautonomias Synucleinopathies

Age range

40 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Meets the 2022 Chinese Expert Consensus Diagnostic Criteria for Clinically Established Multiple System Atrophy (MSA).
  • Unified MSA Rating Scale Part IV (UMSARS-IV) global disability score ≤3.
  • Age: 40-70 years
  • ASA (American Society of Anesthesiologists) Physical Status Classification ≤III, indicating acceptable anesthesia risk.
  • Ability to complete neuropsychological assessments, physical examinations, brain MRI, and venous blood sampling.
  • Willing to participate, provide biospecimens, and sign informed consent.

Exclusion criteria

  • Cognitive/Psychiatric Disorders: Congenital intellectual disability or severe neurological/psychiatric disorders affecting compliance.
  • Severe Comorbidities: End-stage cardiac, hepatic, renal, or respiratory failure, or active malignancy with life expectancy <1 year.
  • Surgical Contraindications:
  • Coagulopathy (uncontrolled bleeding risk)
  • Allergy to surgical drugs/contrast agents
  • Active neck infection (skin/deep tissue)
  • Inability to adhere to study visits.
  • Participation in other competing clinical trials.

Treatment and study plan

Immediate LVA

Procedure

Bilateral cervical lymphatic-venous anastomosis (LVA) performed within 2 weeks after baseline assessments.

Delayed LVA

Procedure

Identical LVA procedure performed at 6 months (±2 weeks) post-baseline

Primary outcomes

  1. Efficacy of Bilateral LVA on MSA Symptoms at 3 Months (UMSARS-II Score Change)

    Time frame: Baseline to 3 months post-operation.

    Description:

    Change in Unified Multiple System Atrophy Rating Scale Part II (UMSARS-II) scores from baseline to 3 months post-LVA surgery.

    Scale Range: 0-56 (higher scores = worse motor function). Metric: Mean difference in total score.

  2. Safety of Bilateral LVA (Surgical Adverse Events)

    Time frame: Intraoperative to 3 months post-operation.

    Incidence of surgery-related adverse events (e.g., infection, bleeding, anastomosis failure) within 3 months post-operation.

    Metric: Percentage of participants with ≥1 adverse event (AE).

Secondary outcomes

  1. Long-term Efficacy of LVA on MSA Symptoms

    Time frame: Baseline to 6, 9, and 12 months post-operation.

    Change in UMSARS-II scores from baseline to 6, 9, and 12 months post-LVA. Scale Range: 0-56 (higher = worse). Metric: Mean difference at each timepoint.

  2. Effect of LVA on Plasma Biomarkers

    Time frame: Baseline to 3 months post-operation.

    Change in plasma biomarkers from baseline to 3 months post-LVA. Metric: Concentration (pg/mL) via ELISA.

  3. Assessment of Glymphatic Function via MRI ALPS Index

    Time frame: Preoperatively (baseline)，3 months post-LVA，12 months post-LVA

    Assessment of Glymphatic Function via MRI ALPS Index Glymphatic activity will be quantitatively evaluated using Diffusion Tensor Imaging along the Perivascular Space (DTI-ALPS) sequence on 3T MRI. The ALPS index will be calculated from diffusivity ratios (Dx/Dz) in the perivascular spaces of deep white matter (centrum semiovale level), reflecting interstitial fluid clearance efficiency. Higher ALPS indices indicate enhanced glymphatic function.

  4. Cognitive Improvement Post-LVA

    Time frame: Baseline to 3, 6, 9, and 12 months post-operation.

    Change in Montreal Cognitive Assessment (MoCA) scores from baseline to 3/6/9/12 months.

    Scale Range: 0-30 (higher = better cognition).

  5. Quality of Life Improvement

    Time frame: Baseline to 3, 6, 9, and 12 months post-operation.

    Change in Parkinson's Disease Questionnaire-39 (PDQ-39) scores from baseline to 3/6/9/12 months.

    Scale Range: 0-100 (lower = better QoL).

  6. Disease-Modifying Effect of LVA (Delayed vs. Immediate Surgery)

    Time frame: Baseline， 3 Months，6 Months，9Months，and 12 Months

    Differences in Unified Multiple System Atrophy Rating Scale Part II (UMSARS-II) Changes from Baseline to 3 Months，6 Months，9Months，and 12 Months

Study contacts

Contact information is provided by the study sponsor or research team.

Chao Gao, MD, PhD

CONTACT

[email protected]

+86 18217590273

Shengdi Chen, MD, PhD

CONTACT

[email protected]

+86 13818018166

Sponsors and collaborators

Lead sponsor

Ruijin Hospital

Other

Registry information

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Jun 25, 2025
Registry last updated
Jun 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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