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

NCT07036939 | Not Yet Recruiting DMC

• 1 other identifier: 2025-264
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple System Atrophy

Keywords

Multiple system atrophy; glymphatic system; lymphatic-venous anastomosis

Outcome Measures

Primary Outcomes (2)

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

  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.

  Baseline to 3 months post-operation.

• Safety of Bilateral LVA (Surgical Adverse Events)

  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).

  Intraoperative to 3 months post-operation.

Secondary Outcomes (6)

• Long-term Efficacy of LVA on MSA Symptoms

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

• Effect of LVA on Plasma Biomarkers

  Baseline to 3 months post-operation.

• Assessment of Glymphatic Function via MRI ALPS Index

  Preoperatively (baseline)，3 months post-LVA，12 months post-LVA

• Cognitive Improvement Post-LVA

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

• Quality of Life Improvement

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

Study Arms (2)

Immediate LVA group

EXPERIMENTAL

Participants will undergo bilateral cervical lymphatic-venous anastomosis (LVA) surgery within 2 weeks after baseline assessments (including clinical scales, biomarker testing, and neuroimaging).

Procedure: Immediate LVA

Delayed LVA Group

ACTIVE COMPARATOR

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

Procedure: Delayed LVA

Interventions

Immediate LVA PROCEDURE

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

Immediate LVA group

Delayed LVA PROCEDURE

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

Delayed LVA Group

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Multiple System Atrophy

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Shengdi Chen, MD, PhD

CONTACT

+86 13818018166; chensd@rjh.com.cn

Chao Gao, MD, PhD

CONTACT

+86 18217590273; anshangaochao@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 17, 2025
• First Posted: June 25, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: June 25, 2025

Record last verified: 2025-06

Locations

CN (1)