Dimethyl Fumarate for Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a common disorder that involves collapse of the upper
airway during sleep, leading to low blood oxygen levels and sleep disruption. Untreated OSA
increases the risk of many health consequences, including high blood pressure, heart
disease, stroke, diabetes, memory problems, fatigue, sleepiness, and impaired memory.
Despite its profound public health and societal impact, there are no known medications that
can effectively treat OSA, and up to 50% of patients cannot tolerate current treatments. The
primary treatment for OSA, known as Continuous Positive Airway Pressure (CPAP), is delivered
by a mechanical device and mask that blows air into the airway to keep it open during sleep.
Although CPAP controls OSA, many patients can't tolerate the discomfort of the mask, and up
to 50% of patients cannot use CPAP appropriately.

Several recent studies of OSA patients suggest that inflammation in the airway and the
bloodstream may worsen OSA, and that medications that control inflammation may improve OSA.
In particular, a previous study from the researchers suggests that multiple sclerosis (MS)
patients who are on MS therapies that control inflammation may have less severe OSA than
those who are not. MS is an autoimmune disease that is associated with inflammation of the
nervous system. As OSA may also be caused or worsened by inflammation, this clinical trial
aims to study the effects of a specific MS medication known as dimethyl fumarate (brand name
- Tecfidera®) to see if it may also be useful to treat OSA. Tecfidera® is already approved
by the Food and Drug Administration (FDA) to treat patients with MS. However, it is not
approved by the FDA for the treatment of OSA and is thus considered an investigational drug
in this study.

Study-related activities will last for 5 months. Consenting participants will receive a
baseline overnight sleep study to assess their current sleep apnea severity. Participants
will then be given either oral dimethyl fumarate or placebo for a period of 4 months, and
will be followed on a monthly basis during the course of the study. At the end of the study,
participants will undergo a repeat overnight sleep study to monitor for changes in their
sleep apnea severity. Treatments will be assigned at random (like flipping a coin), and
participants will not be aware of which treatment they receive. There is a 2/3 chance that
participants will receive dimethyl fumarate. Participants will also undergo blood draws and
complete several surveys during their monthly study visits. Participants will be compensated
for their travel and time throughout the course of the study.

Inclusion Criteria:

1. Age of 18-65 years at screening;

2. Diagnosis of OSA as confirmed by previous clinical sleep study (polysomnography,
PSG);

3. Refusal, inability, or high reluctance to use CPAP regularly for treatment of OSA,
despite medical advice;

4. Willingness to undergo repeat sleep study (PSG) and blood studies;

5. Normal immune cell counts, as evidenced by complete blood count (CBC) done at
screening

Exclusion Criteria:

1. Regular use of CPAP within the last 2 months

2. Physical, psychiatric or cognitive impairment that prevents informed consent, PSG, or
reliable follow-up;

3. Cardiac conditions that may increase sleep apnea severity (e.g., congestive heart
failure or recent heart attack);

4. Current successful treatment for obstructive or central sleep apnea, for example by
CPAP, and patient agreement to continue with that treatment;

5. History of surgical treatment for OSA within past 6 months, or subsequent to last PSG
confirmation that OSA is present;

6. Active nervous system diseases that may predispose subjects to OSA;

7. Systemic autoimmune disease that could increase inflammation and influence apnea
severity (such as rheumatoid arthritis or lupus);

8. Pregnancy or breastfeeding;

9. Use of immunotherapies or immunosuppressants, currently or within past 6 months;

10. Anticipated initiation or dose change in tricyclic antidepressants, selective
serotonin uptake inhibitors, or related compounds;

11. Subjects with a history of active, serious or persistent infections.

12. Subjects with recent surgery (within 3 months prior to screening), or anticipated
surgery during the length of the study.

13. Systemic steroid use within the last 2 months (does not include local steroid
injections or intranasal steroid spray);

14. Current diagnosis of cancer that is not considered to be cured or in remission by the
treating physician, cancer treatment of any kind within the last 6 months prior to
screening (chemo, radiation, surgery), or anticipated cancer treatment during the
length of the study;

15. History of a lymphoproliferative disorder (such as leukemia);

16. History of Multiple Myeloma

17. History of decreased immune cell counts per a blood test known as a CBC, specifically
lymphocyte counts less than 1.2 K/μL at screening.

18. Refusal to use at least one reliable method of birth control (for women of
childbearing age)

19. Newly diagnosed (within 2 months) OSA subjects who have an AHI > 30 and history of
serious, recent, or unstable cardiovascular disease (including but not limited to
recent MI, recent stroke/TIA, or unstable angina)

20. Subjects who report previous motor vehicle accidents or near-misses presumed to be
due to excessive sleepiness while driving.

21. Any other condition or treatment that in the opinion of the investigator could affect
subject safety or study eligibility.