Efficacy and Safety of Modafinil to Treat Fatigue in People With Mitochondrial Disease.

NCT07887412 · tracked via the Priya Life Science Canada tracker

Sponsor

Kenneth Myers, MD

Phase

Phase 3

Started

2026-12-01

Last updated

2026-10-26

Condition(s) studied

Mitochondrial Disease

Investigational drug(s) / intervention(s)

Modafinil (M) →Placebo

Modafinil (M): Formulation: Blue colour capsules, for oral administration, containing 100 mg of active modafinil or matching placebo Route(s) of administration: Oral DOSE REGIMEN Arm 1: Modafinil * Week #1: 2 caps (50 mg) daily (am) * Weeks #2 to 6: 2 caps (50 mg), bid (am and pm) * Week #7: 2 caps (50 mg) daily (am) * Week # 8: Washout Placebo * Week #9: 2 caps daily (am) * Week #10 to 14: 2 caps bid (am and pm) * Week # 15: 2 caps daily (am) OR Arm 2: Placebo * Week #1: 2 caps daily (am) * Week #2 to 6: 2 caps bid (am and pm) * Week #7: 2 caps daily (am) * Week #8: Washout Modafinil * Week #9: 2 caps (50 mg) daily (am) * Weeks #10 to 14: 2 caps (50 mg) bid (am and pm) * Week #15: 2 caps (50 mg) daily (am)

Placebo: Formulation: Blue colour capsules, for oral administration, containing no active modafinil and matching the active modafinil capsules in appearance. Route(s) of administration: Oral DOSE REGIMEN Arm 1: Modafinil Followed by Placebo- Placebo (Cycle 2): Week #9: 2 caps daily (am) Weeks #10 to 14: 2 caps, bid (am and noon) Week #15: 2 caps daily (am) OR Arm 2: Placebo Followed by Modafinil- Placebo (Cycle 1): Week #1: 2 caps daily (am) Weeks #2 to 6: 2 caps, bid (am and noon) Week #7: 2 caps daily (am) Week #8: Washout

Study summary

Mitochondrial diseases are genetic disorders that affect the body's ability to produce energy. Fatigue is a common symptom that can significantly affect daily activities, physical functioning, and quality of life. This study will evaluate whether modafinil, a medication used to promote wakefulness, can improve fatigue and physical endurance in people with mitochondrial disease. The study will also assess the safety and tolerability of modafinil in this population.

Fatigue prevents patients from engaging in activities necessary to maintain a healthy body and adequate brain stimulation. By treating fatigue, we could improve the quality of life of patients with mitochondrial DNA depletion syndrome by promoting better brain stimulation.

15 participants aged 6 to 60 years who have a confirmed diagnosis of mitochondrial disease and clinically significant fatigue will be enrolled. Participants must be able to walk independently for at least 15 meters and meet the other study eligibility criteria.

This is a single-center, randomized, double-blind, placebo-controlled crossover study Participants will be randomly assigned to one of two treatment sequences. One group will receive modafinil first, followed by a placebo, while the other group will receive placebo first, followed by modafinil. Each treatment period will last 7 weeks, with a 1-week washout period between treatments. Modafinil and placebo will be administered orally according to the study dosing schedule. Participants and study investigators /research teams will not know which treatment is being received during each treatment period, only the pharmacy team is unblended and know which study drug vs placebo you are assigned in which group.

The primary outcome measure is the distance walked during the 6-minute walk test, which assesses physical endurance. Secondary outcome measures include walking speed and gait, fatigue severity, the impact of fatigue on daily functioning, and quality of life. Fatigue will be assessed using validated questionnaires appropriate for the participants' age Safety will be evaluated through physical and neurological examinations, blood pressure and heart rate measurements, electrocardiograms, blood tests, and the recording of adverse events.

The treatment period will last approximately 16 weeks per participant, with additional follow-up contact planned for up to 6 months after the participant completes the trial. The study aims to determine whether modafinil improves physical endurance and fatigue in people with mitochondrial disease and to characterize its safety in this population.

Eligibility

Sex

ALL

Min age

6 Years

Max age

60 Years

Healthy volunteers

Inclusion Criteria: * • Written informed consent obtained. * Age 6 - 60 years (Weight ≥ 20 kg). * Genetic diagnosis of a mitochondrial disease. * Clinical diagnosis of a mitochondrial disorder by a neurologist or geneticist. * Patient/family report that fatigue is impacting function and/or quality of life. * Fatigue severity scale (FSS) score \> 36 (patients age 18 years or older) or PROMIS pediatric fatigue score \> 60 (patients aged 6-17 years) * Able to walk at least 15 metres independently. * Have blood pressure values greater than those for the 5th percentile and less than the 95th percentile on the National High Blood Pressure Education Program guidelines for blood pressure levels for boys and girls ages 6 to 16 years * Able to swallow a capsule similar in size and shape to the study drug tablet * Negative urine drug screen (UDS) for any illicit drug, alcohol (ethanol), stimulants at screening; if positive for stimulants (prescribed for excessive sleepiness) at screening, UDS to be repeated after a washout period and before baseline * Females of childbearing age: * Negative urinary pregnancy test at screening * Agree to use effective contraception for the duration of the study Exclusion Criteria: * • Inability of the patient or a parent or legal guardian to give informed consent for any reason. * Cardiac disease * Hepatic dysfunction * Life threatening and/or unstable clinical condition which in the opinion of the investigator might compromise trial completion * Systemic steroid therapy within 30 days * Known hypersensitivity or intolerance, to modafinil or related substances or to any component of the formulation. * Sleep apnea * Narcolepsy * Started an experimental drug in the previous 12 months * Received any investigational drug within 4 weeks of the baseline visit * Any disorder that could interfere with drug absorption, distribution, metabolism, or excretion (including previous gastrointestinal surgery) * Any clinically significant deviation from the normal range(s) in the physical examination or ECG findings, or clinical laboratory test results (ie, serum chemistry, hematology) at the screening or baseline visit * Absolute neutrophil count (ANC) below the lower limit of normal at screening (NOTE: If the ANC is below the lower limit of normal at the baseline visit, the medical monitor will be consulted for continued eligibility in the study.) * A history of alcohol, narcotic, or any other substance abuse * A pregnant or lactating/nursing female * Current or past history of psychosis, mania, major depressive disorder, or other clinically significant psychiatric disorders.

Primary outcome measure(s)

6-Minute Walk Test (6MWT) Distance — Baseline, Visit 2 (42 days) , Visit 3 (56 days) and Visit 4 (98 days)
The 6-minute walk test measures the distance walked in a 6-minute period (in metres), and is a validated measure of exercise endurance that has been used as an outcome in previous clinical trials for mitochondrial disease. The minimum possible distance is 0 metres, with no predefined maximum. Higher distances indicate better functional exercise capacity (better outcome).

Trial sites (1)

Facility	City	Region	Status
Researc Institue of McGill University Health Centre- Children Hospital of Montreal	Montreal	Quebec

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07887412 on ClinicalTrials.gov ↗ ← All trials in Canada