Multiple SclerosisPhase 2MODAFIMSNCT06592352
MODAFIMS: A Trial to Evaluate Predictors of Response to MODAFinil in Patients With Multiple Sclerosis
A Phase 2 study testing Modafinil Generis 100 mg in people with Multiple Sclerosis and Cognitive Impairment, run by Clinical Academic Center (2CA-Braga) at 1 site in Portugal.
Trial summary
This is a phase II/exploratory clinical trial with a single-center, open-label design to evaluate the effect of modafinil on cognitive deficits in adult patients with multiple sclerosis and identify predictors of response using functional Magnetic Resonance Imaging (fMRI). Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Multiple Sclerosis, Cognitive Impairment
- What is being tested?
- Modafinil Generis 100 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 sitePortugal
- Study dates
- 27 Aug 2024to Sep 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Participant is willing and able to give informed consent for the participation in the trial.
- Patients that are able to read and write.
- Male or female, aged between 18 and 64 years old at the time of signing the ICF.
- Diagnosed with Relapsing-Remitting MS or Clinically Isolated Syndrome, according to McDonald 2017 diagnostic criteria (Thompson et al., 2018).
- Expanded disability status score (EDSS) less than 6.5.
- Presence of subjective cognitive complaints.
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- SDMT score (number of correct responses within 90 seconds) at Screening ≤ 55 (Benedict et al., 2016; Parmenter et al., 2007).
- Female participants of childbearing potential and male participants whose partner is of childbearing potential must be willing to ensure that they or their partner use protocol's recommended effective contraception methods, which is not based only on hormonal methods, during all the 6 months of the trial (3 months of treatment plus 3 months of safety follow-up).
- Male participants must agree to refrain from donation of semen from first study treatment administration up to at least 90 days after last administration.
- Participants, that in the medical investigator's opinion, are able and willing to comply with all trial requirements.
Who cannot join
- Female participant who is pregnant, breastfeeding or planning pregnancy during the trial.
- Participants who have participated in another research trial involving an investigational product within the past 5 half-lives of the other investigational product.
- Participants who have any disability that, in the opinion of the investigator, significantly interferes with the neuropsychological testing and/or the tasks in the functional MRI.
- Participants not able to undergo MRI scanning.
- Participants who have any contra-indication for taking modafinil, according to the prescribing information and SmPC, such as hypersensitivity to the active substance and any excipient present in the modafinil or any documented adverse reaction after modafinil intake.
- Participants with known hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
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- Participants with a history of left ventricular hypertrophy or cor pulmonale and patients with mitral valve prolapse who developed mitral valve prolapse syndrome when previously treated with central nervous system stimulants.
- Current use of modafinil, armodafinil.
- Current use of other psychostimulants, including amphetamines, cocaine, bupropion, gingko biloba, among others, and beverages or food containing methylxanthines (e.g., coffee, tea, cola, caffeine, chocolate, sodas) exceeding 500 mg methylxanthines per day (for example, consumption of more than 5 espresso coffees or 100 mg of dark chocolate per day; Sanchez, 2017).
- Significant neurological history aside from MS (e.g., Epilepsy).
- Significant psychiatric history (e.g., Schizophrenia, Bipolar Disorder, Major Depression, severe anxiety disorder, aggressive or hostile behaviour).
- A documented history of attempted suicide in the last 2 years OR suicidal ideation with intent, with or without a plan or method (e.g., positive response to items 4 or 5 in the assessment of suicidal ideation on the C-SSRS) over the 6 months prior to the Screening Visit.
- Significant insomnia (grade \> 1 according to Common Terminology Criteria for Adverse Events, CTCAE v5)
- History of severe hypersensitivity reactions to any medicine.
- Presence of any clinically significant abnormality in ECG morphology or ECG parameters.
- Known immunodeficiency syndrome.
- Have serum alanine aminotransferase (ALT) values greater than 3 times the upper limit of normal at screening.
- Positive test for anti-Human Immunodeficiency virus 1 or 2 antibodies, Hepatitis B surface antigen (HBsAg) or anti Hepatitis C virus antibodies.
- Creatinine clearance \< 20 ml/min determined by Cockcroft-Gault equation.
- History of alcoholism or drug abuse.
- Average daily consumption of more than 20 cigarettes.
- Participants with disability that interferes with the performance of the CT procedures (for example, motor deficit in upper limb, decreased visual acuity even with correction).
- Participants with increased risk of epileptic seizures, history of cardiac arrhythmias, or uncontrolled moderate to severe hypertension.
- Participants taking warfarin or any other prohibited medication.
- Sleep complaints confirmed by Epworth Sleepiness Scale (ESS) scale score \>10 at screening visit OR known sleep disorder.
- Any other condition that, in the opinion of the investigator, contra-indicates the participation of the patient.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Portugal1 site, 1 recruiting
- Recruiting
Clinical Academic Center - Braga (2CA-Braga)
Braga, 4710-243
João Cerqueira, MD, PhD, +351253027249, joao.cerqueira@ccabraga.org
João Cerqueira, MD, PhD
About this study
Official title: MODAFIMS: An Open-label, Single-center Clinical Trial to Evaluate Predictors of Response to MODAFinil in the Treatment of Cognitive Deficits in Patients With Multiple Sclerosis
This is a phase II/exploratory clinical trial with a single-center, open-label design to evaluate the effect of modafinil on cognitive deficits in adult patients with multiple sclerosis and identify predictors of response using functional Magnetic Resonance Imaging (fMRI).
Read the detailed description
Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. There are no commercially authorized therapeutic options available for the treatment of cognitive impairment in patients with multiple sclerosis. It is then necessary to conduct robust clinical trials to select better therapies.
Modafinil is a drug approved by INFARMED and European Medicines Agency (EMA) for the treatment of excessive sleepiness associated with narcolepsy. Modafinil has been tested in 5 clinical trials in patients with multiple sclerosis and the results indicated a potential improvement in cognitive deficits in tasks that measure executive function, verbal memory, and/or working memory performance.
Despite encouraging results, there is a huge variation in its effect in individual patients and a significant proportion of sub-optimal/non-responders. Therefore, it is important to identify personalized predictors of response to best tailor the treatment to each patient.
This is a phase II/exploratory clinical trial with a single-center, open-label design to evaluate the effect of modafinil on cognitive deficits in adult patients with multiple sclerosis and identify predictors of response using functional Magnetic Resonance Imaging (fMRI).
The primary objective of the clinical trial is to identify fMRI markers of response to modafinil. In other words, our aim is to analyse brain activity (using fMRI) before and after modafinil intake and select the features that can better differentiate between responders and non-responders. These patient groups will be determined according to the improvement rate in the Symbol digit modalities test (SDMT) - which will be evaluated at screening, baseline and at the end of treatment.
The clinical trial will be conducted at Centro Clínico Académico - Braga, Associação (2CA-Braga), Unidade Local de Saúde de Braga (ULS Braga), E.P.E.. Participants will be recruited at the outpatient unit of the Neurology department of ULS de Braga.
A total of 64 eligible patients will be enrolled to receive modafinil at a dose 200 mg (2 tablets of 100 mg) once per day in the morning for 3 months.
- Conditions
- Multiple Sclerosis, Cognitive Impairment
- Being tested
- Modafinil Generis 100 mg
- Keywords
- multiple sclerosis, cognitive impairment, functional MRI
- Medical subject headings
- Multiple Sclerosis, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modafinil Generis 100 mgDrug
Also called Modafinil Generis
All participants enrolled in the study will receive the study intervention drug (Modafinil Generis 100 mg). Dose 200 mg once per day (2 tablets of 100 mg) in the morning for 3 months (84 days), Oral administration
| Study group | Role | What they receive |
|---|---|---|
| Modafinil Generis 100 mg | Experimental | Modafinil Generis 100 mg, in a dose of 200mg, once a day, orally. Receives: Drug: Modafinil Generis 100 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute changes in brain fuction and connectivity measured using resting state fMRI.
Acute changes in brain functional connectivity at rest will be measured using resting-state fMRI through Echo-planar imaging (EPI) sequences.
Measured: Day 1 (baseline): before and 3 hours (± 30 minutes) after modafinil administration.
Long-term changes in brain function and connectivity measured using resting state fMRI.
Long-term changes inbrain functional connectivity at rest will be measured using resting-state fMRI through Echo-planar imaging (EPI) sequences.
Measured: Day 1 (baseline), 3 hours (± 30 minutes) after medication; and Day 84 (3 months after treatment with modafinil), 3 hours (±30 minutes) after medication.
Secondary outcomes (8)
Acute changes in brain function and connectivity measured using a Go/no-Go task fMRI.
Acute changes in brain activity during a Go/No-Go task, measured using task-based fMRI through Echo-planar imaging (EPI) sequences.
Measured: Baseline (day 1): before and 3 hours (± 30 minutes) after modafinil administration.
Long-term changes in brain function and connectivity measured using a Go/no-Go task fMRI.
Long-term changes in brain activity during a Go/No-Go task, measured using task-based fMRI through Echo-planar imaging (EPI) sequences.
Measured: Day 1 (baseline), 3 hours (± 30 minutes) after medication; and Day 84 (3 months after treatment with modafinil), 3 hours (±30 minutes) after medication.
SDMT score
Symbol Digit Modalities Test (SDMT) is a cognitive function test to assess visual attention and information processing speed, which involves a simple substitution task. The SDMT includes a reference key of 9 symbols, each paired with a single digit. Below the reference key are rows of symbols arranged randomly. The participant will have 90 seconds to say out loud the number that corresponds to each symbol. Answers are registered by the rater in the SDMT form and the score corresponds to the number of correct answers given within the 90-seconds interval. A decrease of 4 points from baseline on the SDMT is considered a meaningful worsening.
Measured: Day 1 (baseline) and Day 84 (3 months after treatment)
Stroop test
The Stroop test is a measure of executive function, including selective attention capacity, processing speed, behaviour inhibition and interference resistance. The performance in this test is measured by the interference index.
Measured: Screening and Day 84 (3 months after treatment)
MS-QoL-54 total score
Multiple Sclerosis Quality of Life-54 (MS-QoL-54) is a multidimensional health-related quality of life (QoL) measure combining generic and MS-specific items into a single tool. MS-QoL-54 has a total of 54-items generating 12 subscales along with two summary scores, and two additional single-item measures. The subscales are: physical function, role limitations-physical, role limitations-emotional, pain, emotional well-being, energy, health perceptions, social function, cognitive function, health distress, overall QoL, and sexual function.
The single item measures are satisfaction with sexual function and change in health. The summary scores are the physical health composite summary and the mental health composite summary. Scores range from 0 to 100, with higher values representing a better QoL.
Measured: Screening and Day 84 (3 months after treatment).
WPAI:MS total score
The Work Productivity and Activity Impairment Questionnaire for MS is a 6-item questionnaire which measures the impact of MS on the patients' work productivity (including the duration of work time missed due to the disease and decrease in productivity when working while experiencing symptoms) and non-working activities (for example, childcare) during the past seven days.
Measured: Screening and Day 84 (3 months after treatment).
MFIS total score
The Modified Fatigue Impact Scale (MFIS) is a 21-item tool used to rate the impact of fatigue during the last 4 weeks on a 5-point Likert scale, from "Never" (0) to "Almost always" (4). The total score is the sum of all items from 0 to 84, with higher scores indicating greater impact of fatigue.
Measured: Screening and Day 84 (3 months after treatment).
PDQ total score
Perceived Deficits Questionnaire (PDQ) is a 20-items self-report measure to assess perceived cognitive impairment during the past 4 weeks. The total score ranges from 0 to 80, and higher scores reflect greater perceived cognitive impairment.
Measured: Screening and Day 84 (3 months after treatment with modafinil)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start27 Aug 2024
- Primary completionJun 2026 (estimated)
- Study completionSep 2026 (estimated)
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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- single-center, open-label design to evaluate the effect of modafinil on cognitive deficits in adult patients with multiple sclerosis and identify predictors of response using functional Magnetic Resonance Imaging (fMRI).
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinical Academic Center (2CA-Braga)
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- João Cerqueira, MD, PhD, Principal investigator, 2CA-Braga
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06592352
- Sponsor's protocol ID
- MODAFIMS
- Other IDs
- 2022-501414-53-00
- Acronym
- MODAFIMS
- Status last verified
- Aug 2025
- First submitted
- 3 Apr 2024
- Last updated
- 13 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MODAFIMS: An Open-label, Single-center Clinical Trial to Evaluate Predictors of Response to MODAFinil in the Treatment of Cognitive Deficits in Patients With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT06592352
- Acronym / sponsor ID
- MODAFIMS / MODAFIMS
- Conditions
- Multiple Sclerosis, Cognitive Impairment
- Keywords
- multiple sclerosis, cognitive impairment, functional MRI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Clinical Academic Center (2CA-Braga)University, hospital or other
- Study start
- 27 Aug 2024 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 19 Sep 2024 (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.
This is a phase II/exploratory clinical trial with a single-center, open-label design to evaluate the effect of modafinil on cognitive deficits in adult patients with multiple sclerosis and identify predictors of response using functional Magnetic Resonance Imaging (fMRI).
Detailed description
Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. There are no commercially authorized therapeutic options available for the treatment of cognitive impairment in patients with multiple sclerosis. It is then necessary to conduct robust clinical trials to select better therapies.
Modafinil is a drug approved by INFARMED and European Medicines Agency (EMA) for the treatment of excessive sleepiness associated with narcolepsy. Modafinil has been tested in 5 clinical trials in patients with multiple sclerosis and the results indicated a potential improvement in cognitive deficits in tasks that measure executive function, verbal memory, and/or working memory performance.
Despite encouraging results, there is a huge variation in its effect in individual patients and a significant proportion of sub-optimal/non-responders. Therefore, it is important to identify personalized predictors of response to best tailor the treatment to each patient.
This is a phase II/exploratory clinical trial with a single-center, open-label design to evaluate the effect of modafinil on cognitive deficits in adult patients with multiple sclerosis and identify predictors of response using functional Magnetic Resonance Imaging (fMRI).
The primary objective of the clinical trial is to identify fMRI markers of response to modafinil. In other words, our aim is to analyse brain activity (using fMRI) before and after modafinil intake and select the features that can better differentiate between responders and non-responders. These patient groups will be determined according to the improvement rate in the Symbol digit modalities test (SDMT) - which will be evaluated at screening, baseline and at the end of treatment.
The clinical trial will be conducted at Centro Clínico Académico - Braga, Associação (2CA-Braga), Unidade Local de Saúde de Braga (ULS Braga), E.P.E.. Participants will be recruited at the outpatient unit of the Neurology department of ULS de Braga.
A total of 64 eligible patients will be enrolled to receive modafinil at a dose 200 mg (2 tablets of 100 mg) once per day in the morning for 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single-center, open-label design to evaluate the effect of modafinil on cognitive deficits in adult patients with multiple sclerosis and identify predictors of response using functional Magnetic Resonance Imaging (fMRI).
| Arm | Type | Receives |
|---|---|---|
| Modafinil Generis 100 mg | Experimental | Drug: Modafinil Generis 100 mgModafinil Generis 100 mg, in a dose of 200mg, once a day, orally. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Participant is willing and able to give informed consent for the participation in the trial.
- Patients that are able to read and write.
- Male or female, aged between 18 and 64 years old at the time of signing the ICF.
- Diagnosed with Relapsing-Remitting MS or Clinically Isolated Syndrome, according to McDonald 2017 diagnostic criteria (Thompson et al., 2018).
- Expanded disability status score (EDSS) less than 6.5.
Key exclusion criteria (26 listed)
- Female participant who is pregnant, breastfeeding or planning pregnancy during the trial.
- Participants who have participated in another research trial involving an investigational product within the past 5 half-lives of the other investigational product.
- Participants who have any disability that, in the opinion of the investigator, significantly interferes with the neuropsychological testing and/or the tasks in the functional MRI.
- Participants not able to undergo MRI scanning.
- Participants who have any contra-indication for taking modafinil, according to the prescribing information and SmPC, such as hypersensitivity to the active substance and any excipient present in the modafinil or any documented adverse reaction after modafinil intake.
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 |
|---|---|---|
| Modafinil Generis 100 mgAlso: Modafinil GenerisAll participants enrolled in the study will receive the study intervention drug (Modafinil Generis 100 mg). Dose 200 mg once per day (2 tablets of 100 mg) in the morning for 3 months (84 days), Oral administration | Drug | Modafinil Generis 100 mg |
Primary outcome
Acute changes in brain fuction and connectivity measured using resting state fMRI.
Time frame: Day 1 (baseline): before and 3 hours (± 30 minutes) after modafinil administration.
Acute changes in brain functional connectivity at rest will be measured using resting-state fMRI through Echo-planar imaging (EPI) sequences.
Long-term changes in brain function and connectivity measured using resting state fMRI.
Time frame: Day 1 (baseline), 3 hours (± 30 minutes) after medication; and Day 84 (3 months after treatment with modafinil), 3 hours (±30 minutes) after medication.
Long-term changes inbrain functional connectivity at rest will be measured using resting-state fMRI through Echo-planar imaging (EPI) sequences.
8 secondary outcomes
Acute changes in brain function and connectivity measured using a Go/no-Go task fMRI.
Time frame: Baseline (day 1): before and 3 hours (± 30 minutes) after modafinil administration.
Long-term changes in brain function and connectivity measured using a Go/no-Go task fMRI.
Time frame: Day 1 (baseline), 3 hours (± 30 minutes) after medication; and Day 84 (3 months after treatment with modafinil), 3 hours (±30 minutes) after medication.
SDMT score
Time frame: Day 1 (baseline) and Day 84 (3 months after treatment)
Stroop test
Time frame: Screening and Day 84 (3 months after treatment)
MS-QoL-54 total score
Time frame: Screening and Day 84 (3 months after treatment).
WPAI:MS total score
Time frame: Screening and Day 84 (3 months after treatment).
MFIS total score
Time frame: Screening and Day 84 (3 months after treatment).
PDQ total score
Time frame: Screening and Day 84 (3 months after treatment with modafinil)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2025.
- Individual participant dataSharing planned: No
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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.
João Cerqueira, MD, PhD principal investigator
2CA-Braga
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Modafinil Generis 100 mg in people with Multiple Sclerosis and Cognitive Impairment, run by Clinical Academic Center (2CA-Braga) at 1 site in Portugal.
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 10 inclusion and 26 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: looking for participants now, as of the sponsor's last update on 13 Aug 2025. 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 Portugal. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mónica Gonçalves (+351 253 027 249, 2ca@ccabraga.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute changes in brain fuction and connectivity measured using resting state fMRI. (time frame: Day 1 (baseline): before and 3 hours (± 30 minutes) after modafinil administration.). The study lists 2 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 13 Aug 2025.