Dalfampridine in Egyptian Patients With Multiple Sclerosis

Effect of Dalfampridine on Gait Impairment, Cognition and Fatigue in Egyptian Patients With Multiple Sclerosis

The only approved treatment for impaired ambulation in MS is Dalfampridine (also known as fampridine, 4-aminopyridine, 4-AP). Fampridine penetrates the blood-brain barrier and improves impaired axonal conduction by selectively blocking potassium channels. Moreover, further studies investigated the possible beneficial effect of dalfampridine on cognitive functions and fatigue.

The main objective of this study is to investigate the effect of dalfampridine on gait impairment, cognitive functions and fatigue in a sample of Egyptian patients with multiple sclerosis.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Dalfampridine ER, 10 Mg Oral Tablet, Extended Release; Drug: Placebo

Detailed Description

Type of the Study: randomized double blinded placebo controlled study. Study Setting: MS outpatient clinic in Ain Shams University hospital and Dar Alshefa Hospital, they are located in Eastern Cairo and serves large sector of the ministry of health patients in Greater Cairo.

Period two years. Population patients with relapsing remittent multiple sclerosis attending to ms clinic meeting the inclusion criteria.

Sample size: 100 patients (50 patients in active group and 50 patients in placebo group).

Study Procedures:

Patients diagnosed with MS will be evaluated for inclusion and exclusion criteria using the selected screening scales. Eligible patients will be randomly assigned to one of two groups: dalfampridine ER 10mg twice daily group and placebo group for 12 consecutive weeks.

All patients will be subjected to:

Comprehensive medical history and neurological examination. Demographic information (sex, age and education years), as well as clinical characteristics of them (age at onset, duration of illness, onset of last relapse, received DMD and other medications during the study).

MRI brain and spine lesions (site & number of lesions). Check list for side effects of dalfampridine. Expanded Disability Status Scale (EDSS) (Kurtzke, 1983). The Patient Health Questionnaire (PHQ-9) Arabic translation (Kroenke et al., 2001).

Gait assessment by:

• Timed 25 foot walk test (25FWT) (Motl et al., 2017).
• Hauser ambulatory index (Hauser et al., 1983).
• Berg balance scale (Berg et al., 1992).
• Falls in last 2 weeks.

Cognitive assessment by:

• Arabic validated version of the BICAM battery, which compromised the symbol digit modality test (SDMT, information processing speed), verbal learning test (VLT, verbal memory) and brief visuospatial memory teat revised (BVMT-R, visual memory) (Alboudi et al., 2020).
• Montreal Cognitive Assessment (MoCA) Arabic version (Abd El-Rahman and El-Gaafary, 2009).
• Frontal assessment battery (FAB) (for executive functions) (Dubois and Litvan, 2000).

Fatigue assessment by:

o Modified fatigue impact scale (MFIS) in last 4 weeks Arabic version (Farran et al., 2020).

• Assessment for gait, cognition and fatigue will be done at baseline and after 12 weeks of treatment by a blinded rater.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ali Shalash, PhD; Phone Number: 01111124815; Email: ali_neuro@yahoo.com
• Study Contact Backup: Name: Eman Hamid, MD

Study Locations

• Egypt
  • Cairo, Egypt, 11591
    • Recruiting
    • Ain Shams Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years.
• Individuals diagnosed with RRMS based on revised McDonald Criteria 2017
• Patients with Expanded Disability Status Scale (EDSS) ≤ 5.5
• Patients with gait impairment according to 25 foot walk test (25FWT) with cutoff ≥ 4 seconds

Exclusion Criteria:

• Women who are pregnant, intended to be pregnant or breastfeeding.
• Past History of epilepsy or trigeminal neuralgia.
• History of any psychiatric or medical illness affecting cognition and fatigue.
• Other comorbidities that might affect gait.
• Clinical relapse in the last three months.
• Uncooperative patients or couldn't perform the required scales.
• Patients with moderate to severe depression according to patient health questionnaire (PHQ-9) with cutoff point ≥15.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: dalfampridine; patients received dalfampridine ER 10mg twice daily	Drug: Dalfampridine ER, 10 Mg Oral Tablet, Extended Release; The only approved treatment for impaired ambulation in MS is Dalfampridine (also known as fampridine, 4-aminopyridine, 4-AP). Fampridine penetrates the blood-brain barrier and improves impaired axonal conduction by selectively blocking potassium channels
Placebo Comparator: Placebo; patients received placebo	Drug: Placebo; placebo similar to Dalfampridine capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gait	Timed 25 foot walk test (25FWT), higher scores mean a worse outcome	at 3 months
gait	Hauser ambulatory index, higher scores mean a worse outcome	3 months
Balance	Berg balance scale, higher scores mean a worse outcome	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cognition	Arabic validated version of the BICAM battery	3 months
fatigue	Modified fatigue impact scale: physical, 0 to 36; cognitive, 0 to 40; and psychosocial, 0 to 8. higher scores mean a worse outcome	3 months
cognition	MOCA, higher scores mean a better outcome	3 months
Cognition	frontal assessment battery	3 months

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: December 5, 2021
• First Submitted That Met QC Criteria: February 15, 2023
• First Posted (Estimate): February 16, 2023

Study Record Updates

• Last Update Posted (Estimate): February 16, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Gait; cognition; Fatigue; Multiple sclerosis,; Dalfampridine
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Potassium Channel Blockers; 4-Aminopyridine
• Other Study ID Numbers: FMASU MD 551/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No