Clinical trial NCT05811949: Effects of Dimethyl Fumarate on Cognitive Performance and Brain Abnormalities in Multiple Sclerosis.
Official title: Effects of Dimethyl Fumarate on Cognitive Performances and Gray Matter and Thalamic Pathology in Multiple Sclerosis: a Correlation Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Lead sponsor: IRCCS Centro Neurolesi Bonino Pulejo
Sponsor class: OTHER
First posted: 2023-04-13
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study is conducted in 52 patients: twenty-six de novo MS patients who start DMF treatment and 26 patients who switch from first-line DMT treatment (interferon, glatiramer acetate, teriflunomide) to treatment with DMF are matched for age and gender. Sample size calculation considers a significance level of 5% and a power of 80% to detect a difference of 0.22 with a standard deviation of 0.5, assuming a patients' loss of 20-30%.

Brief summary: The goal of this observational study is to evaluate the slowing/reduction of cognitive dysfunction progression and to evaluate grey matter (GM) and thalamus structural changes in Relapsing-Remitting Multiple Sclerosis (RRMS) patients after 12 months of treatment with Dimethyl Fumarate (DMF).

The main questions it aims to answer are:

* Can DMF slow or reduce the progression of cognitive dysfunction in RRMS patients?
* Can DMF slow the reduction of brain volume in RRMS patients?

At baseline visit, RRMS patients undergo extensive neurological examination in which their disability is evaluated by using Expanded Disability Status Scale (EDSS). The efficacy assessments of this study are:

1. The Brief Repeatable Neuropsychological Battery (BRB);
2. Executive functions: Delis-Kaplan Function System (DKEFS) scale - Sorting Test.

All RRMS patients undergo MRI: conventional MRI measures (T2-, T1-enhancing and T1-hypointense lesions), global brain atrophy, regional brain atrophy and Diffusion Tensor Imaging (DTI) (GM and thalamus) examinations.

Six and 12 months after the baseline visit, the RRMS patients in treatment with DMF undergo the BRB, DKEFS and MRI/DTI study and neurological evaluation (EDSS).

Detailed description: Dimethyl fumarate (DMF) is an oral disease-modifying therapy (DMT) approved for management of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. Clinical trials have shown that DMF has a significant beneficial impact on relapse rate, disability accrual and the number of new lesions along with their volumes. In addition, a neuroprotective role of DMF has been suggested to occur on both the gray matter (GM) and thalamus. However, there are no correlation data in the literature between the effects of DMF on cognitive performance and those on the GM, with a focus on thalamic pathology in MS patients.

The primary objectives of this study are:

i) to evaluate the slowing/reduction of cognitive dysfunction progression in RRMS patients after 12 months of treatment with DMF; ii) to evaluate the effects of DMF on Magnetic Resonance Imaging (MRI) parameters in GM and thalamus.

The secondary objective is to evaluate how the effects on cognitive dysfunction progression are associated to the effect of slowing the brain volume reduction at MRI (antiatrophic effect) and to change of Diffusion Tensor Imaging (DTI) parameters that DMT might have in RRMS patients, in the GM and thalamus.

The tertiary objective is to assess whether differences exist between patients with RRMS de novo to DMF treatment and patients switching from first-line DMT to DMF.

After signing informed consent, demographics, medical history and current therapies are collected for each RRMS patient enrolled. RRMS patients undergo extensive neurological examination in which their disability is evaluated by using EDSS. The efficacy assessments of this study are:

1. The Brief Repeatable Neuropsychological Battery (BRB)
2. Executive functions: Delis-Kaplan Function System (DKEFS) scale - Sorting Test.

All MS patients undergo MRI: conventional MRI measures (T2-, T1-enhancing and T1-hypointense lesions), global brain atrophy, regional brain atrophy and DTI (GM and thalamus) examinations.

Six and 12 months after the baseline visit, the RRMS patients in treatment with DMF undergo the BRB, DKEFS and MRI/DTI study and neurological evaluation (EDSS).

Eligibility criteria: Inclusion Criteria:

* Patients must voluntarily give written informed consent. Patients must read and fully understand the Informed Consent Form (ICF);
* Patient diagnosed with MS according to McDonald criteria;
* Adult patients, males or female patients ≥ 18 years old;
* Relapsing disease course;
* Expanded Disability Status Scale (EDSS) ≤5.5;
* Patients who initiate treatment with DMF 240 mg twice daily according prescribing criteria.

Exclusion Criteria:

* Diagnosis of non-relapsing MS;
* Use of experimental drug or investigational procedure during the study period;
* Pregnancy;
* Severe hepatic impairment;
* Relapse or corticosteroid use within 30 days prior to baseline MRI scan;
* Previous use of alemtuzumab, cladribine, rituximab, or mitoxantrone.

Primary outcomes:
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Change in subjects' cognitive performance
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Changes brain MRI parameters
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Changes brain MRI parameters
timeFrame: Month 0 Baseline to Month 12 Follow-up
measure: Changes brain MRI parameters
timeFrame: Month 0 Baseline to Month 6 Follow-up
measure: Changes brain MRI parameters
timeFrame: Month 0 Baseline to Month 12 Follow-up
Secondary outcomes:
measure: Correlation between scores of cognitive battery and brain MRI parameters
timeFrame: Baseline and 6 and 12 months after.
Other outcomes:
measure: Difference between the two cohorts
timeFrame: Baseline and 6 and 12 months after.
Locations:
city: Messina
country: Italy
facility: IRCCS Centro Neurolesi "Bonino-Pulejo"
Study officials:
References: