Multiple SclerosisNCT05811949
Effects of Dimethyl Fumarate on Cognitive Performance and Brain Abnormalities in Multiple Sclerosis.
An observational study of Multiple Sclerosis, run by IRCCS Centro Neurolesi Bonino Pulejo at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Dimethyl Fumarate 240 MG [Tecfidera]
- How many people
- 52 participants
- Where
- 1 siteItaly
- Study dates
- 24 Feb 2021to 7 Jun 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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%.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Dimethyl Fumarate on Cognitive Performances and Gray Matter and Thalamic Pathology in Multiple Sclerosis: a Correlation Study.
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:
Read more
- 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:
- The Brief Repeatable Neuropsychological Battery (BRB);
- 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).
Read the 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).
- Conditions
- Multiple Sclerosis
- Being tested
- Dimethyl Fumarate 240 MG [Tecfidera]
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dimethyl Fumarate 240 MG [Tecfidera]Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| RRMS patients with de novo DMF treatment | RRMS patients with de novo treatment who start DMF. Receives: Drug: Dimethyl Fumarate 240 MG [Tecfidera] | |
| RRMS patients switching to DMF. | RRMS patients who switch from first-line DMT treatment (interferon, glatiramer acetate, teriflunomide) to treatment with DMF. Receives: Drug: Dimethyl Fumarate 240 MG [Tecfidera] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in subjects' cognitive performance
Change from baseline in Selective Reminding Test - Long-Term Storage (SRT-LTS) Raw Score of Brief Repeatable Battery (BRB) at 6 months. This is one of the five tests of BRB for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total score ranged from 0 to 72. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 6 Follow-up
Change in subjects' cognitive performance
Change from baseline in Selective Reminding Test - Consistent Long Term Retrieval (SRT-CLTR) Raw Score of Brief Repeatable Battery (BRB) at 6 months. This is one of the five tests of BRB for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. If a word in LTS is consistently recalled on all subsequent trials, it is then scored as Consistent Long Term Retrieval (CLTR). The total of the words in CLTR of all six trials is summed. The total score ranged from 0 to 72. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 6 Follow-up
Change in subjects' cognitive performance
Change from baseline in Spatial Recall Test (SPART) Raw Score of Brief Repeatable Battery (BRB) at 6 months. The spatial recall test assesses visuospatial learning and delayed recall. The total score ranged from 0 to 30. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 6 Follow-up
Change in subjects' cognitive performance
Change from baseline in Symbol Digit Modalities Test (SDMT) Raw Score of Brief Repeatable Battery (BRB) at 6 months. Symbol Digit Modality Test (SDMT) for sustained attention and information processing speed. The score is the number of correct answers in 90 seconds. The total score ranged from 0 to 110. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 6 Follow-up
Change in subjects' cognitive performance
Change from baseline in Paced Auditory Serial Addition Test - 3 Seconds (PASAT 3) Raw Score of Brief Repeatable Battery (BRB) at 6 months. Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The total score ranged from 0 to 60. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 6 Follow-up
Change in subjects' cognitive performance
Change from baseline in Paced Auditory Serial Addition Test - 2 (PASAT 2) Raw Score of Brief Repeatable Battery (BRB) at 6 months. Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The total score ranged from 0 to 60. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 6 Follow-up
Change in subjects' cognitive performance
Change from baseline in Selective Reminding Test - Delayed Recall (SRT-D) Raw Score of Brief Repeatable Battery (BRB) at 6 months. The tests SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall).The total score ranged from 0 to 12. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 6 Follow-up
Change in subjects' cognitive performance
Change from baseline in Spatial Recall Test - Delayed Recall (SPART-D) of Brief Repeatable Battery (BRB) at 6 months. Spatial Recall Test (SPART) for visuospatial learning and delayed recall. Spatial Recall Test (10/36): The spatial recall test assesses visuospatial learning and delayed recall (10/36-D). The total score ranged from 0 to 10. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 6 Follow-up
Change in subjects' cognitive performance
Change from baseline in Word List Generation (WLG) of Brief Repeatable Battery (BRB) at 6 months. Word List Generation (COWAT/WLG): The COWAT assesses verbal fluency on semantic stimulus by asking the patient to produce as many words as possible belonging to a semantic category. No maximum range is available. Higher values represent a better outcome. The score is the number of correct words. The more words the patient pronounces, the better it is. We can imagine that the minimum value might be zero words, but it is not a score scale.
Measured: Month 0 Baseline to Month 6 Follow-up
Change in subjects' cognitive performance
Change from baseline in Selective Reminding Test - Long-Term Storage (SRT-LTS) Raw Score of Brief Repeatable Battery (BRB) at 12 months. One of the five tests of BRB is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total score ranged from 0 to 72. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 12 Follow-up
Change in subjects' cognitive performance
Change from baseline in Selective Reminding Test - Consistent Long Term Retrieval (SRT-CLTR) Raw Score of Brief Repeatable Battery (BRB) at 12 months. One of the five tests of BRB is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. If a word in LTS is consistently recalled on all subsequent trials, it is then scored as Consistent Long Term Retrieval (CLTR). The total of the words in CLTR of all six trials is summed. The total score ranged from 0 to 72. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 12 Follow-up
Change in subjects' cognitive performance
Change from baseline in Spatial Recall Test (SPART) Raw Score of Brief Repeatable Battery (BRB) at 12 months. The spatial recall test assesses visuospatial learning and delayed recall. The total score ranged from 0 to 30. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 12 Follow-up
Change in subjects' cognitive performance
Change from baseline in Symbol Digit Modalities Test (SDMT) Raw Score of Brief Repeatable Battery (BRB) at 12 months. Symbol Digit Modality Test (SDMT) for sustained attention and information processing speed. The score is the number of correct answers in 90 seconds. The total score ranged from 0 to 110. Higher values represent a better outcome
Measured: Month 0 Baseline to Month 12 Follow-up
Change in subjects' cognitive performance
Change from baseline in Paced Auditory Serial Addition Test - 3 Seconds (PASAT 3) Raw Score of Brief Repeatable Battery (BRB) at 12 months. Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The total score ranged from 0 to 60. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 12 Follow-up
Change in subjects' cognitive performance
Change from baseline in Paced Auditory Serial Addition Test - 2 (PASAT 2) Raw Score of Brief Repeatable Battery (BRB) at 12 months. +Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The total score ranged from 0 to 60. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 12 Follow-up
Change in subjects' cognitive performance
Change from baseline in Selective Reminding Test - Delayed Recall (SRT-D) Raw Score of Brief Repeatable Battery (BRB) at 12 months. The tests SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall).The total score ranged from 0 to 12. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 12 Follow-up
Change in subjects' cognitive performance
Change from baseline in Spatial Recall Test - Delayed Recall (SPART-D) of Brief Repeatable Battery (BRB) at 12 months. Spatial Recall Test (SPART) for visuospatial learning and delayed recall.Spatial Recall Test (10/36): The spatial recall test assesses visuospatial learning and delayed recall (10/36-D). The total score ranged from 0 to 10. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 12 Follow-up
Change in subjects' cognitive performance
Change from baseline in Word List Generation (WLG) of Brief Repeatable Battery (BRB) at 12 months. Word List Generation (COWAT/WLG): The COWAT assesses verbal fluency on semantic stimulus by asking the patient to produce as many words as possible belonging to a semantic category. No maximum range is available. Higher values represent a better outcome. The score is the number of correct words. The more words the patient pronounces, the better it is. We can imagine that the minimum value might be zero words, but it is not a score scale.
Measured: Month 0 Baseline to Month 12 Follow-up
Change in subjects' cognitive performance
Change from baseline in Delis-Kaplan Executive Function System (DKEFS) Condition 1: Free Sorting, Confirmed Correct Sort - Card Set 1+2 at 6 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. The DKFES test consisted of two testing procedures: free sorting and sort recognition. In free sorting, six scores are obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) is obtained, as well as the sum of description scores of both sets. The total score ranges from 0 to 16. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 6 Follow-up
Change in subjects' cognitive performance
Change from baseline in DKEFS Condition 1: Free Sorting, Free Sorting, Description Score, Card Set 1+2 at 6 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) was obtained, as well as the sum of description scores of both sets. The total score ranged from 0 to 64. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 6 Follow-up
Change in subjects' cognitive performance
Change from baseline in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score- Card Set 1+22 at 6 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. Free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. The total score ranged from 0 to 64. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 6 Follow-up
Change in subjects' cognitive performance
Change from baseline in Delis-Kaplan Executive Function System (DKEFS) Condition 1: Free Sorting, Confirmed Correct Sort - Card Set 1+2 at 12 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. The DKFES test consisted of two testing procedures: free sorting and sort recognition. In free sorting, six scores are obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) is obtained, as well as the sum of description scores of both sets. The total score ranges from 0 to 16. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 12 Follow-up
Change in subjects' cognitive performance
Change from baseline in DKEFS Condition 1: Free Sorting, Free Sorting, Description Score, Card Set 1+2 at 12 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) was obtained, as well as the sum of description scores of both sets. The total score ranged from 0 to 64. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 12 Follow-up
Change in subjects' cognitive performance
Change from baseline in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score - Card Set 1+22 at 12 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. Free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. The total score ranged from 0 to 64. Higher values represent a better outcome.
Measured: Month 0 Baseline to Month 12 Follow-up
Changes brain MRI parameters
Change from baseline GM and thalamus volume at 6 months.
Measured: Month 0 Baseline to Month 6 Follow-up
Changes brain MRI parameters
Change from baseline GM and thalamus volume at 12 months.
Measured: Month 0 Baseline to Month 12 Follow-up
Changes brain MRI parameters
Change from baseline DTI measures in the GM and thalamus at 6 months.
Measured: Month 0 Baseline to Month 6 Follow-up
Changes brain MRI parameters
Change from baseline DTI measures in the GM and thalamus at 12 months.
Measured: Month 0 Baseline to Month 12 Follow-up
Secondary outcomes (1)
Correlation between scores of cognitive battery and brain MRI parameters
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.
Measured: Baseline and 6 and 12 months after.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2023
- Study start24 Feb 2021
- Primary completion11 Oct 2022
- Study completion7 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS Centro Neurolesi Bonino Pulejo
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05811949
- Sponsor's protocol ID
- MSDMF_2020
- Status last verified
- Oct 2024
- First submitted
- 17 Mar 2023
- Last updated
- 15 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Dimethyl Fumarate on Cognitive Performances and Gray Matter and Thalamic Pathology in Multiple Sclerosis: a Correlation Study.
- ClinicalTrials.gov ID
- NCT05811949
- Acronym / sponsor ID
- MSDMF_2020
- Conditions
- Multiple Sclerosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- IRCCS Centro Neurolesi Bonino PulejoUniversity, hospital or other
- Study start
- 24 Feb 2021 (actual)
- Primary completion
- 11 Oct 2022 (actual)
- Study completion
- 7 Jun 2023 (actual)
- First posted
- 13 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- The Brief Repeatable Neuropsychological Battery (BRB);
- 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:
- 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RRMS patients with de novo DMF treatment | – | Drug: Dimethyl Fumarate 240 MG [Tecfidera]RRMS patients with de novo treatment who start DMF. |
| RRMS patients switching to DMF. | – | Drug: Dimethyl Fumarate 240 MG [Tecfidera]RRMS patients who switch from first-line DMT treatment (interferon, glatiramer acetate, teriflunomide) to treatment with DMF. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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%.
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | RRMS patients switching to DMF., RRMS patients with de novo DMF treatment |
Primary outcome
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline in Selective Reminding Test - Long-Term Storage (SRT-LTS) Raw Score of Brief Repeatable Battery (BRB) at 6 months. This is one of the five tests of BRB for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total score ranged from 0 to 72. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline in Selective Reminding Test - Consistent Long Term Retrieval (SRT-CLTR) Raw Score of Brief Repeatable Battery (BRB) at 6 months. This is one of the five tests of BRB for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. If a word in LTS is consistently recalled on all subsequent trials, it is then scored as Consistent Long Term Retrieval (CLTR). The total of the words in CLTR of all six trials is summed. The total score ranged from 0 to 72. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline in Spatial Recall Test (SPART) Raw Score of Brief Repeatable Battery (BRB) at 6 months. The spatial recall test assesses visuospatial learning and delayed recall. The total score ranged from 0 to 30. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline in Symbol Digit Modalities Test (SDMT) Raw Score of Brief Repeatable Battery (BRB) at 6 months. Symbol Digit Modality Test (SDMT) for sustained attention and information processing speed. The score is the number of correct answers in 90 seconds. The total score ranged from 0 to 110. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline in Paced Auditory Serial Addition Test - 3 Seconds (PASAT 3) Raw Score of Brief Repeatable Battery (BRB) at 6 months. Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The total score ranged from 0 to 60. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline in Paced Auditory Serial Addition Test - 2 (PASAT 2) Raw Score of Brief Repeatable Battery (BRB) at 6 months. Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The total score ranged from 0 to 60. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline in Selective Reminding Test - Delayed Recall (SRT-D) Raw Score of Brief Repeatable Battery (BRB) at 6 months. The tests SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall).The total score ranged from 0 to 12. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline in Spatial Recall Test - Delayed Recall (SPART-D) of Brief Repeatable Battery (BRB) at 6 months. Spatial Recall Test (SPART) for visuospatial learning and delayed recall. Spatial Recall Test (10/36): The spatial recall test assesses visuospatial learning and delayed recall (10/36-D). The total score ranged from 0 to 10. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline in Word List Generation (WLG) of Brief Repeatable Battery (BRB) at 6 months. Word List Generation (COWAT/WLG): The COWAT assesses verbal fluency on semantic stimulus by asking the patient to produce as many words as possible belonging to a semantic category. No maximum range is available. Higher values represent a better outcome. The score is the number of correct words. The more words the patient pronounces, the better it is. We can imagine that the minimum value might be zero words, but it is not a score scale.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline in Selective Reminding Test - Long-Term Storage (SRT-LTS) Raw Score of Brief Repeatable Battery (BRB) at 12 months. One of the five tests of BRB is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total score ranged from 0 to 72. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline in Selective Reminding Test - Consistent Long Term Retrieval (SRT-CLTR) Raw Score of Brief Repeatable Battery (BRB) at 12 months. One of the five tests of BRB is SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall). A word recalled on two consecutive trials is considered to have entered long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total of the words in LTS of all six trials is then summed. If a word in LTS is consistently recalled on all subsequent trials, it is then scored as Consistent Long Term Retrieval (CLTR). The total of the words in CLTR of all six trials is summed. The total score ranged from 0 to 72. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline in Spatial Recall Test (SPART) Raw Score of Brief Repeatable Battery (BRB) at 12 months. The spatial recall test assesses visuospatial learning and delayed recall. The total score ranged from 0 to 30. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline in Symbol Digit Modalities Test (SDMT) Raw Score of Brief Repeatable Battery (BRB) at 12 months. Symbol Digit Modality Test (SDMT) for sustained attention and information processing speed. The score is the number of correct answers in 90 seconds. The total score ranged from 0 to 110. Higher values represent a better outcome
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline in Paced Auditory Serial Addition Test - 3 Seconds (PASAT 3) Raw Score of Brief Repeatable Battery (BRB) at 12 months. Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The total score ranged from 0 to 60. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline in Paced Auditory Serial Addition Test - 2 (PASAT 2) Raw Score of Brief Repeatable Battery (BRB) at 12 months. +Paced Auditory Serial Addition Test (PASAT) for working memory (and sustained attention and information processing speed). The total score ranged from 0 to 60. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline in Selective Reminding Test - Delayed Recall (SRT-D) Raw Score of Brief Repeatable Battery (BRB) at 12 months. The tests SRT (Selective Reminding Test) for episodic memory (verbal learning and delayed recall).The total score ranged from 0 to 12. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline in Spatial Recall Test - Delayed Recall (SPART-D) of Brief Repeatable Battery (BRB) at 12 months. Spatial Recall Test (SPART) for visuospatial learning and delayed recall.Spatial Recall Test (10/36): The spatial recall test assesses visuospatial learning and delayed recall (10/36-D). The total score ranged from 0 to 10. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline in Word List Generation (WLG) of Brief Repeatable Battery (BRB) at 12 months. Word List Generation (COWAT/WLG): The COWAT assesses verbal fluency on semantic stimulus by asking the patient to produce as many words as possible belonging to a semantic category. No maximum range is available. Higher values represent a better outcome. The score is the number of correct words. The more words the patient pronounces, the better it is. We can imagine that the minimum value might be zero words, but it is not a score scale.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline in Delis-Kaplan Executive Function System (DKEFS) Condition 1: Free Sorting, Confirmed Correct Sort - Card Set 1+2 at 6 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. The DKFES test consisted of two testing procedures: free sorting and sort recognition. In free sorting, six scores are obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) is obtained, as well as the sum of description scores of both sets. The total score ranges from 0 to 16. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline in DKEFS Condition 1: Free Sorting, Free Sorting, Description Score, Card Set 1+2 at 6 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) was obtained, as well as the sum of description scores of both sets. The total score ranged from 0 to 64. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score- Card Set 1+22 at 6 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. Free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. The total score ranged from 0 to 64. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline in Delis-Kaplan Executive Function System (DKEFS) Condition 1: Free Sorting, Confirmed Correct Sort - Card Set 1+2 at 12 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. The DKFES test consisted of two testing procedures: free sorting and sort recognition. In free sorting, six scores are obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) is obtained, as well as the sum of description scores of both sets. The total score ranges from 0 to 16. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline in DKEFS Condition 1: Free Sorting, Free Sorting, Description Score, Card Set 1+2 at 12 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. In sort recognition, a description score for card set 1 and 2 (or 3 and 4 for version B) was obtained, as well as the sum of description scores of both sets. The total score ranged from 0 to 64. Higher values represent a better outcome.
Change in subjects' cognitive performance
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score - Card Set 1+22 at 12 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. Free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. The total score ranged from 0 to 64. Higher values represent a better outcome.
Changes brain MRI parameters
Time frame: Month 0 Baseline to Month 6 Follow-up
Change from baseline GM and thalamus volume at 6 months.
Changes brain MRI parameters
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline GM and thalamus volume at 12 months.
Changes brain MRI parameters
Time frame: 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
Time frame: Month 0 Baseline to Month 12 Follow-up
Change from baseline DTI measures in the GM and thalamus at 12 months.
1 secondary outcome
Correlation between scores of cognitive battery and brain MRI parameters
Time frame: Baseline and 6 and 12 months after.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by IRCCS Centro Neurolesi Bonino Pulejo at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in subjects' cognitive performance (time frame: Month 0 Baseline to Month 6 Follow-up). The study lists 28 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.