Exploration of the Association Between White Matter Lesion Burden and Dalfampridine Response in Insidious-Onset Vascular Parkinsonism (DAL-VaP)

An Exploratory Cohort Study to Evaluate Whether White Matter Lesion Burden Correlates With Dalfampridine Response in Insidious-Onset Vascular Parkinsonism and Parkinson-Plus Syndromes

This single-center observational cohort study will be conducted at Tangdu Hospital, Fourth Military Medical University. Patients presenting parkinsonism and poor levodopa response will be enrolled, including insidious-onset vascular parkinsonism (VaP) and Parkinson-plus syndromes (PPS). Within each diagnostic subgroup, participants will receive either dalfampridine 10 mg twice daily for 4 weeks combined with conventional therapy, or conventional therapy alone. Change in Timed Up and Go (TUG) time, gait speed, balance, daily function, and quality of life metrics assessed from baseline to Week 4.

Study Overview

• Status: Completed
• Conditions: Vascular Parkinsonism

Detailed Description

Insidious-onset vascular parkinsonism (VaP) is characterized by typical clinical manifestations including gait impairment, postural instability, poor levodopa responsiveness, and diffuse cerebral white matter lesions (WMLs). Dalfampridine is an agent indicated to manage gait dysfunction among patients diagnosed with multiple sclerosis. This study will collect standardized gait and functional scale assessments in participants with insidious-onset VaP and participants with Parkinson-plus syndromes (PPS).

Single-center observational cohort study performed at Tangdu Hospital, Fourth Military Medical University, Xi'an, China. Parkinsonism and poor levodopa response will be divided into two diagnostic subgroups (VaP, PPS). Each subgroup will receive one of two treatment regimens: dalfampridine 10 mg twice daily for 4 weeks plus conventional therapy, or conventional therapy alone.

Change in Timed Up and Go (TUG) test time,10-meter walking speed, Tinetti scale score, ADL scale score, FES-I score, FOG-Q score, and SF-36 summary scores recorded at baseline and Week 4 among participants with VaP.

Baseline white matter lesion volume will be documented as a baseline clinical characteristic of all enrolled participants.

• Study Type: Observational
• Enrollment (Actual): 72

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710038
      • Tangdu Hospital, Fourth Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with insidious-onset vascular parkinsonism or Parkinson-plus syndromes, with gait impairment and poor levodopa response.

Description

Inclusion Criteria:

• Age ≥ 18 years
• Clinical diagnosis of insidious-onset vascular parkinsonism or Parkinson-plus syndromes
• Gait, balance, or mobility impairment
• Poor levodopa response (<10% improvement in UPDRS-III after levodopa challenge)
• Ability to complete all study assessments

Exclusion Criteria:

• Seizure disorder or epilepsy
• Multiple sclerosis
• Repeated traumatic brain injury
• Encephalitis, brain tumor, or normal-pressure hydrocephalus
• Severe peripheral neuropathy
• Severe systemic illness or active infection
• Other neurological/psychiatric conditions interfering with assessments

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
VaP + Dalfampridine; Patients with insidious-onset vascular parkinsonism treated with dalfampridine 10 mg twice daily plus conventional therapy for 4 weeks.
VaP + Conventional Therapy; Patients with insidious-onset vascular parkinsonism treated with conventional therapy alone for 4 weeks.
PPS + Dalfampridine; Patients with Parkinson-plus syndromes treated with dalfampridine 10 mg twice daily plus conventional therapy for 4 weeks.
PPS + Conventional Therapy; Patients with Parkinson-plus syndromes treated with conventional therapy alone for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Timed Up and Go (TUG) Time From Baseline to Week 4	Change in the time taken to complete the Timed Up and Go (TUG) test from baseline to Week 4.	Baseline to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 10-Meter Walk Test Speed From Baseline to Week 4	Change in speed during the 10-Meter Walk Test from baseline to Week 4.	Baseline to Week 4
Change in Tinetti Balance and Gait Scale Score From Baseline to Week 4	Change in total score on the full Tinetti Balance and Gait Scale from baseline to Week 4. The scale ranges from 0 to 28; higher scores indicate superior balance and walking function.	Baseline to Week 4
Change in Activities of Daily Living (ADL) Scale Score From Baseline to Week 4	Change in total score on the full Activities of Daily Living (ADL) Scale from baseline to Week 4. Scores range from 0 to 100; higher scores reflect better daily living performance.	Baseline to Week 4
Change in Falls Efficacy Scale-International (FES-I) Score From Baseline to Week 4	Change in total score on the full Falls Efficacy Scale-International (FES-I) from baseline to Week 4. Scores range from 16 to 64; higher scores correspond to greater fear of falling.	Baseline to Week 4
Change in Freezing of Gait Questionnaire (FOG-Q) Score From Baseline to Week 4	Change in total score on the full Freezing of Gait Questionnaire (FOG-Q) from baseline to Week 4. Scores range from 0 to 24; higher scores mean more severe gait freezing symptoms.	Baseline to Week 4
Change in SF-36 Physical and Mental Component Summary Scores From Baseline to Week 4	Change in Physical Component Summary and Mental Component Summary scores on the full SF-36 Health Survey from baseline to Week 4. Each summary score ranges from 0 to 100; higher scores represent better physical or mental health status.	Baseline to Week 4

Collaborators and Investigators

• Sponsor: Tang-Du Hospital
• Investigators: Principal Investigator: Wei Zhang, MD, PhD, Tang-Du Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): January 31, 2025

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 28, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 28, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Vascular parkinsonism; Dalfampridine; Parkinson-plus syndromes; Gait impairment; White matter lesions
• Other Study ID Numbers: K202307-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No