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

NCT07887412 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: RIMUHC
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mitochondrial Disease

Keywords

Mitochondrial Diseases, Fatigue, Modafinil

Outcome Measures

Primary Outcomes (1)

• 6-Minute Walk Test (6MWT) Distance

  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.

  Baseline, Visit 2 (42 days) , Visit 3 (56 days) and Visit 4 (98 days)

Secondary Outcomes (2)

• 10-Metre Walk Assessment (10 MWA) Distance

  Baseline, Visit 2 (42 days) , Visit 3 (56 days) and Visit 4 (98 days)

• Fatigue Scale

  Baseline, Visit 2 (42 days) , Visit 3 (56 days) and Visit 4 (98 days)

Study Arms (2)

Modafinil

EXPERIMENTAL

Cycle 1 Modafinil vs Cycle 2 Placebo

Drug: Modafinil (Placebo)

Placebo

PLACEBO COMPARATOR

Cycle 1 Placebo vs Cycle 2 Modafinil

Drug: Modafinil (Placebo)

Interventions

Modafinil (Placebo) DRUG

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)

Modafinil; Placebo

Eligibility Criteria

• Age: 6 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kenneth Myers, MD: lead

Study Sites (1)

Researc Institue of McGill University Health Centre- Children Hospital of Montreal

Montreal, Quebec, H4A 3H9, Canada

Location

MeSH Terms

Conditions

Mitochondrial Diseases; Fatigue

Interventions

Modafinil

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Dr. Kenneth Myers, MD, PhD, Associate Professor

CONTACT

514-934-1934; kenneth.myers@mcgill.ca

Research Team, PhD

CONTACT

514-934-1934; myersresearch@rimuhc.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Division Director of Child Neurology (Division Director, Pediatric Neurology) at the Montreal Children's Hospital and an Associate Professor in the Department of Pediatrics and Department of Neurology & Neurosurgery at McGill University.

Study Record Dates

• First Submitted: October 14, 2026
• First Posted: October 21, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): January 31, 2031
• Last Updated: October 21, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)