Dalfampridine in Egyptian Patients With Multiple Sclerosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Dalfampridine ER, 10 Mg Oral Tablet, Extended Release
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: dalfampridine<br>patients received dalfampridine ER 10mg twice daily | Drug: Dalfampridine ER, 10 Mg Oral Tablet, Extended Release<br>* 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<br>|
| Placebo Comparator: Placebo<br>patients received placebo | Drug: Placebo<br>* placebo similar to Dalfampridine capsule<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple sclerosis,, Dalfampridine, Gait, cognition, Fatigue