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

Not Applicable

Not yet recruiting

• Conditions: Multiple System Atrophy

• Registration Number: NCT07036939
• Lead Sponsor: Ruijin Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-17
• Study First Submitted QC: 2025-06-17
• Last Update Submitted: 2025-06-17
• Study First Posted: 2025-06-25
• Last Update Posted: 2025-06-25
• Study Start: 2025-07-01
• Primary Completion: 2028-04-30
• Study Completion: 2028-04-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 46

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Efficacy of Bilateral LVA on MSA Symptoms at 3 Months (UMSARS-II Score Change)	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.
Safety of Bilateral LVA (Surgical Adverse Events)	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 Outcome Measures

Name	Time	Method
Long-term Efficacy of LVA on MSA Symptoms	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.
Effect of LVA on Plasma Biomarkers	Baseline to 3 months post-operation.	Change in plasma biomarkers from baseline to 3 months post-LVA. Metric: Concentration (pg/mL) via ELISA.
Assessment of Glymphatic Function via MRI ALPS Index	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.
Cognitive Improvement Post-LVA	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).
Quality of Life Improvement	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).
Disease-Modifying Effect of LVA (Delayed vs. Immediate Surgery)	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

Trial Locations

Locations (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China