Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system. Typical brain lesions of the disease may be partially repaired by an endogenous remyelination process which is limited and tends to deplete over the course of the disease. Cladribine tablets are an approved treatment that promotes selective lymphocyte depletion, reducing the inflammatory activity of the disease. The present study is based on the hypothesis that improved inflammatory control through cladribine tablets provides a tissue microenvironment more favorable for remyelination of brain lesions in MS. This hypothesis will be evaluated by a single-arm, open-label, phase IV, single-center, proof-of-concept clinical trial in which 10 participants with relapsing-remitting, highly active MS, relatively early in the course of the disease, will receive conventional treatment with cladribine tablets and will be followed-up for 48 months. Neurological, neuropsychological and magnetic resonance imaging (MRI) parameters will be measured. Remyelination will be assessed by a novel MRI technique called the q-Space myelin map. Additionally, the peripheral blood lymphocyte and cytokine profiles will be evaluated in order to understand the immunological aspects that influence the remyelination capacity in patients treated with cladribine tablets. The study will be conducted in accordance with current regulations governing clinical research in Brazil.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Cladribine tablets (Mavenclad®, Merck KGaA, Darmstadt, Germany) will be given according to the label with a cumulative dose of 3.5 mg/kg body weight distributed over 2 years as one treatment course of 1.75 mg/kg per year. Each treatment course will consist of 2 weeks of treatment, one at the beginning of the first month and one at the beginning of the second month of the respective year of treatment. Each treatment week will consist of 4 or 5 days in which the participant will receive 10 mg or 20 mg (1 or 2 tablets, respectively) as a single daily dose, depending on body weight, according to the tables available in label. Upon completion of the two treatment courses, no further courses will be required in years 3 and 4.
Pontifical Catholic University of Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, Brazil
Proportion of remyelinated lesions (as assessed by neuroradiologist) in q-Space myelin map
Time frame: 36 months after initiation of cladribine tablets treatment
Median "lesion ratio" (i.e., myelin index: lesion signal / normal appearing white matter signal) in q-Space myelin map
Time frame: 36 months after initiation of cladribine tablets treatment
Mean signal intensity of lesions in q-Space myelin map
Time frame: 36 months after initiation of cladribine tablets treatment
Correlation between lymphocyte profile and remyelination parameters in q-Space myelin map
Time frame: Transversally (at months 0, 12, 24, and 36) and longitudinally (over 36 months following initiation of cladribine tablets treatment)
Correlation between cytokine profile and remyelination parameters in q-Space myelin map
Time frame: Transversally (at months 0, 12, 24, and 36) and longitudinally (over 36 months following initiation of cladribine tablets treatment)
Correlation between remyelination parameters in q-Space myelin map and evolution of clinical scores (annualized relapse rate, EDSS, MSFC and their subtests)
Time frame: Over 36 months following initiation of cladribine tablets treatment
Correlation between remyelination parameters in q-Space myelin map and evolution of neuropsychological scores (BICAMS and MFIS subtests)
Time frame: Over 36 months following initiation of cladribine tablets treatment
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