Modafinil for Fatigue in Mitochondrial Disease

This trial aims to determine if modafinil, a medication that promotes wakefulness, can reduce fatigue and enhance physical endurance in individuals with mitochondrial disease, a genetic condition that hinders energy production. The study will compare modafinil to a placebo to assess its effectiveness and safety. Suitable candidates for this trial include those aged 6 to 60 with a confirmed mitochondrial disease and fatigue that disrupts daily life, who can walk at least 15 meters independently. Participants will take both modafinil and a placebo at different times, each for seven weeks, with a break in between. The trial will measure the distance participants can walk in six minutes to evaluate improvement. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment's journey toward becoming widely available.

Research has shown that modafinil is generally well-tolerated and has been tested for safety in various conditions. For example, in individuals with ALS (a disease affecting muscle control), modafinil did not cause serious side effects. One study found it safe for patients experiencing sleepiness due to conditions like sleep apnea (a disorder where breathing repeatedly stops and starts during sleep).

In these studies, most participants did not experience serious harmful effects. The medication has been tested in over 3,500 people, providing a good understanding of its safety. While some side effects, such as headaches or nausea, can occur, they are usually mild and manageable.

Most treatments for mitochondrial disease-related fatigue focus on managing symptoms through lifestyle changes and supplements. But Modafinil works differently, targeting the brain’s neurotransmitters to promote wakefulness and reduce fatigue. Researchers are excited because Modafinil has the potential to improve energy levels and quality of life more effectively than current options. Additionally, its unique mechanism could offer relief to patients who have not found success with traditional treatments.

Research has shown that modafinil can help reduce tiredness in various conditions. Studies have found that people taking modafinil daily experienced a significant drop in fatigue levels, improving by 33-38 points on a fatigue measurement scale compared to their starting scores. Modafinil has also been used to lessen tiredness related to cancer and has shown promise in conditions like amyotrophic lateral sclerosis (ALS), where it was well-tolerated and helped reduce fatigue symptoms. While some results vary, modafinil is known for its ability to fight excessive sleepiness and improve alertness, making it a possible option for those with fatigue due to mitochondrial diseases. In this trial, participants will receive modafinil in one cycle and a placebo in another cycle to evaluate its effectiveness specifically for fatigue in mitochondrial disease.⁶⁷⁸⁹¹⁰