MODAFIMS: A Trial to Evaluate Predictors of Response to MODAFinil in Patients With Multiple Sclerosis

NCT06592352 | Recruiting Phase 2

• 2 other identifiers: MODAFIMS2022-501414-53-00
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Multiple Sclerosis; Cognitive Impairment

Keywords

multiple sclerosis; cognitive impairment; functional MRI

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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.

  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.

  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

  Day 1 (baseline) and Day 84 (3 months after treatment)

• Stroop test

  Screening and Day 84 (3 months after treatment)

• MS-QoL-54 total score

  Screening and Day 84 (3 months after treatment).

Study Arms (1)

Modafinil Generis 100 mg

EXPERIMENTAL

Modafinil Generis 100 mg, in a dose of 200mg, once a day, orally.

Drug: Modafinil Generis 100 mg

Interventions

Modafinil Generis 100 mg DRUG

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

Also known as: Modafinil Generis

Modafinil Generis 100 mg

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Clinical Academic Center (2CA-Braga): lead

Study Sites (1)

Clinical Academic Center - Braga (2CA-Braga)

Braga, 4710-243, Portugal

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• João Cerqueira, MD, PhD

  2CA-Braga

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mónica Gonçalves

CONTACT

+351 253 027 249; 2ca@ccabraga.org

Rosana Magalhães

CONTACT

+351 253 027 249; cro@ccabraga.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: April 3, 2024
• First Posted: September 19, 2024
• Study Start: August 27, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: August 13, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)