Effect of Dalfampridine in Patients With Hereditary Spastic Paraplegia

There are limited but encouraging results supporting the use of dalfampridine in patients with hereditary spastic paraplegia. The investigators aimed to investigate the effects of dalfampridine on walking speed, muscle length, spasticity, functional strength, and functional mobility in patients with hereditary spastic paraplegia. In this triple-blinded, randomized, placebo-controlled trial, 4 patients with hereditary spastic paraplegia received dalfampridine (10 mg twice daily) plus physiotherapy (2 times per week), and 4 patients received placebo plus physiotherapy for a total duration of 8 weeks. The assessor and treating physiotherapists, and patients were masked to the group allocation. The primary outcome was Timed 25-foot Walk Test at the end of the 8-week treatment. The secondary outcome measures were functional mobility, functional muscle strength, muscle length, and spasticity.

Study Overview

• Status: Completed
• Conditions: Hereditary Spastic Paraplegia
• Intervention / Treatment: Drug: Dalfampridine 10 MG; Behavioral: Physiotherapy; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Cyprus
  • Nicosia, Cyprus
    • Dr. Burhan Nalbantoğlu State Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of Hereditary Spastic Paraplegia at least 1 year ago

Exclusion Criteria:

• Having another neurological disorder
• An orthopedic deformity in the lower extremity
• Having a serious cognitive impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medication; Dalfampridine plus physiotherapy	Drug: Dalfampridine 10 MG; The participants in the experimental group received dalfampridine administered as 10 mg extended-release tablets every twelve hours for 8 weeks.; Behavioral: Physiotherapy; Conventional physiotherapy program including stretching and flexibility, strengthening, walking and balance exercises which were mainly focused on the lower limbs and improving walking. The program was applied 2 times per week for the total duration of 8 weeks.
Placebo Comparator: No Medication; Placebo plus physiotherapy	Behavioral: Physiotherapy; Conventional physiotherapy program including stretching and flexibility, strengthening, walking and balance exercises which were mainly focused on the lower limbs and improving walking. The program was applied 2 times per week for the total duration of 8 weeks.; Drug: Placebo; Control group received a placebo drug with the same administration method (2 times per week for the total duration of 8 weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Timed 25-foot Walk Test	The Timed 25-foot walk test (T25FW) is considered the "best characterized objective measure of walking disability and can be used across a wide range of walking disabilities". For the T25-FW, patients were instructed to walk as fast as they could in a safemanner along amarked 25-foot course. The time in seconds to complete each test was recorded, and the test was immediately repeated.	Change from baseline to week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sit to Stand Test	30 second Chair-Stand Test which is a reliable and valid measure used to assess lower extremity strength and endurance is used where the number of sitting and getting up within 30 seconds gives the score of the test.	Change from baseline to week 8
Timed Up and Go test	Functional mobility was evaluated using the Timed up and Go Test 'TUG' test, which is also reliable and valid test for people with Parkinson's disease. (Morris2001; Van2016). Upon issuing the command "Go," the participants stood up from a normal chair, walked 3 meters, turned, walked back to the chair, and sat. The time began with the command "Go" and ended when the participants sat back to the chair. This test was repeated three times, and the shortest performance time was recorded	Change from baseline to week 8
Modified Ashworth Scale	Modified Ashworth Scale (MAS) is one of the reliable and valid methods to measure muscle spasticity. The procedure to evaluate specific muscle groups; passively moved through the range of motion of a limb, and the resistance encountered during muscle stretch is rated on a five-point scale. Ashworth defines this rating as; 0 = no increase in tone, 1 = slight increase in tone at the end of the range of motion, 1+ = slight increase in tone throughout less than half the range of motion, 2 = increased muscle tone throughout the full range of motion, but passive movement is present. 3=tone movement that makes passive movement difficult, 4=rigidity .	Change from baseline to week 8
Muscle Length Measurement	Bilateral muscle length measurements were obtained using a standard goniometer. The patient positioned in supine position; the dorsiflexion has been tested for the gastrocnemius, the straight leg rise - hip angle has been measured to assess hamstrings, the Thomas test was used to assess iliopsoas and hip abduction angle was used for adductor group muscles.	Change from baseline to week 8

Collaborators and Investigators

• Sponsor: European University of Lefke
• Investigators: Principal Investigator: Ferda Selcuk, European University of Lefke

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2020
• Primary Completion (Actual): March 12, 2021
• Study Completion (Actual): March 12, 2021

Study Registration Dates

• First Submitted: November 4, 2022
• First Submitted That Met QC Criteria: November 4, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): November 22, 2022
• Last Update Submitted That Met QC Criteria: November 17, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Manifestations; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Paralysis; Muscle Hypertonia; Polyneuropathies; Hereditary Sensory and Motor Neuropathy; Muscle Spasticity; Paraplegia; Spastic Paraplegia, Hereditary; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Potassium Channel Blockers; 4-Aminopyridine
• Other Study ID Numbers: 45/20

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