ew strategies for diagnostic, therapeutic and clinical care in neurological diseases

Phase 1

• Conditions: Multiple sclerosis with cerebellar ataxia; MedDRA version: 20.1Level: PTClassification code 10028245Term: Multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2014-004650-34-IT
• Lead Sponsor: IRCCS FONDAZIONE ISTITUTO NEUROLOGICO NAZIONALE C. MONDINO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-11-05
• Last Update Posted: 5 January 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

Aged 18–70 years,
With clinically defined multiple sclerosis (McDonald 2010),
Able to complete two trials of the timed 25-foot walk (T25FW)
EDSS between 4 and 6,
International Cooperative Ataxia Rating Scale (ICARS) walking capacities score =2,
Pyramidal Functional System Score (FSS) =2.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

Onset of multiple sclerosis exacerbation within 90 days of screening,
A history of seizures a history of seizures or the presence of vascular, infectious or methabolic lesions of the cerebral cortex leading to symptomatic seizures,
Allergy to pyridine or tablet excipients
Patients treated with drugs containing 4-aminopyridine,
Any condition that would interfere with the conduct or interpretation of the study,
Contraindication to the use of the Transcranial Magnetic Stimulator,
Clinically significant abnormal laboratory values or electrocardiogram at screening,
Patients with impaired renal function mild, moderate or severe (creatinine cleareance <80 ml/min),
Patients treated with OCT2 inhibitors, for example cimetidine,
Women were excluded if they were pregnant, lactating or of childbearing potential and not using adequate birth control.

We set additional restrictions on changes in concomitant medications to avoid related changes in multiple sclerosis symptoms during the trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety and clinical effectiveness of cerebellar TBS and 4-aminopiridine for enhancing the effects of gait rehabilitation;Secondary Objective: To describe the behavioural changes in motor control and learning induced by cerebellar iTBS and by 4-AP, and to detect the associated changes in the cerebello-cortical circuits in multiple sclerosis (MS) patients with CGA;Primary end point(s): we expect to find a >21.43% difference between the treatment (baseline/end of treatment T25FT score ratio: mean 1.4, SD 0.17) and the placebo group (baseline/end of treatment T25FT score ratio: mean 1.1, SD 0.04).;Timepoint(s) of evaluation of this end point: At the end of the two-week experimental treatment period (day 14) with respect to baseline.