Effects of Dimethyl Fumarate on Cognitive Performance and Brain Abnormalities in Multiple Sclerosis.
Study Details
Study Description
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:
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Can DMF slow or reduce the progression of cognitive dysfunction in RRMS patients?
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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:
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The Brief Repeatable Neuropsychological Battery (BRB);
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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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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:
- 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:
-
The Brief Repeatable Neuropsychological Battery (BRB)
-
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| RRMS patients with de novo DMF treatment RRMS patients with de novo treatment who start DMF. |
Drug: Dimethyl Fumarate 240 MG [Tecfidera]
DMF is admnistered to RRMS patients who are candidates for treatment according to clinical practice at a dosage of 120 mg twice daily, increased to 240 mg twice daily after 7 days.
|
| RRMS patients switching to DMF. RRMS patients who switch from first-line DMT treatment (interferon, glatiramer acetate, teriflunomide) to treatment with DMF. |
Drug: Dimethyl Fumarate 240 MG [Tecfidera]
DMF is admnistered to RRMS patients who are candidates for treatment according to clinical practice at a dosage of 120 mg twice daily, increased to 240 mg twice daily after 7 days.
|
Outcome Measures
Primary Outcome Measures
- Change in subjects' cognitive performance [Month 0 Baseline to Month 6 Follow-up]
Change from baseline Brief Repeatable Battery (BRB) score at 6 months.
- Change in subjects' cognitive performance [Month 0 Baseline to Month 12 Follow-up]
Change from baseline Brief Repeatable Battery (BRB) score at 12 months.
- Change in subjects' cognitive performance [Month 0 Baseline to Month 6 Follow-up]
Change from baseline Delis-Kaplan Executive Function System scale (DKEFS) - Sorting Test score at 6 months.
- Change in subjects' cognitive performance [Month 0 Baseline to Month 12 Follow-up]
Change from baseline Delis-Kaplan Executive Function System scale (DKEFS) - Sorting Test score at 12 months.
- Changes brain MRI parameters [Month 0 Baseline to Month 6 Follow-up]
Change from baseline GM and thalamus volume at 6 months.
- Changes brain MRI parameters [Month 0 Baseline to Month 12 Follow-up]
Change from baseline GM and thalamus volume at 12 months.
- Changes brain MRI parameters [Month 0 Baseline to Month 6 Follow-up]
Change from baseline DTI measures in the GM and thalamus at 6 months.
- Changes brain MRI parameters [Month 0 Baseline to Month 12 Follow-up]
Change from baseline DTI measures in the GM and thalamus at 12 months.
Secondary Outcome Measures
- Correlation between scores of cognitive battery and brain MRI parameters [Baseline and 6 and 12 months after.]
Correlation data between each test of cognitive battery, in terms of mean changes in total score observed at endpoint vs. baseline, and brain volume reduction and DTI parameters (in GM and thalamus), as mean change after 12 months of treatment.
Other Outcome Measures
- Difference between the two cohorts [Baseline and 6 and 12 months after.]
Difference between the two cohorts in terms of mean changes in total score of BRB and DKEFS scale and in terms of mean changes in brain volume and DTI parameters (in GM and thalamus).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients must voluntarily give written informed consent. Patients must read and fully understand the Informed Consent Form (ICF);
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Patient diagnosed with MS according to McDonald criteria;
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Adult patients, males or female patients ≥ 18 years old;
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Relapsing disease course;
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Expanded Disability Status Scale (EDSS) ≤5.5;
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Patients who initiate treatment with DMF 240 mg twice daily according prescribing criteria.
Exclusion Criteria:
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Diagnosis of non-relapsing MS;
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Use of experimental drug or investigational procedure during the study period;
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Pregnancy;
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Severe hepatic impairment;
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Relapse or corticosteroid use within 30 days prior to baseline MRI scan;
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Previous use of alemtuzumab, cladribine, rituximab, or mitoxantrone.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | IRCCS Centro Neurolesi "Bonino-Pulejo" | Messina | Italy | 98124 |
Sponsors and Collaborators
- IRCCS Centro Neurolesi "Bonino-Pulejo"
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MSDMF_2020