Dimethyl Fumarate for Obstructive Sleep Apnea

NCT ID: NCT02438137

Last Updated: 2017-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2016-05-31

Brief Summary

The overall purpose of this study is to determine whether the oral medication dimethyl fumarate is an effective treatment for obstructive sleep apnea in patients who are unable, unwilling, or uneager to use positive airway pressure therapy.

Detailed Description

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.

Conditions

Obstructive Sleep Apnea; OSA; Sleep Apnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Dimethyl Fumarate (Tecfidera®) capsules

The starting dose for dimethyl fumarate (Tecfidera®, http://www.tecfidera.com/pdfs/full-prescribing-information.pdf) is 120 mg twice a day orally. After 7 days, the dose should be increased to the maintenance dose of 240 mg twice a day, though slower dose escalations are possible to increase tolerability, if necessary. Participants randomized to dimethyl fumarate will be instructed to take this medication twice a day with breakfast and dinner for a period of 4 months.

Group Type: ACTIVE_COMPARATOR

Dimethyl fumarate

Intervention Type: DRUG

Dimethyl fumarate capsules will be dispensed during routine study appointments. 120 mg tablets will be dispensed to facilitate dose titrations. Drug will be dispensed in 1 month supply, so that compliance can be reconciled at monthly follow-up visits, and recorded in accountability logs. Participants will be instructed to take the medication with food, in the morning and at dinnertime. If participants miss a dose, they will be instructed to resume their normal dose at the next scheduled time, and be instructed not to take an extra dose at their next dosing interval if they previously miss a dose.

Placebo

The placebo is an inert product that looks like a pill and is identical to dimethyl fumarate capsules, but it contains no medicine. Participants randomized to placebo will be instructed to take placebo twice a day with breakfast and dinner for a period of 4 months.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsules will be dispensed during routine study appointments. Placebo will be dispensed in 1 month supply, so that compliance can be reconciled at monthly follow-up visits, and recorded in accountability logs. Participants will be instructed to take the placebo with food, in the morning and at dinnertime. If participants miss a dose, they will be instructed to resume their normal dose at the next scheduled time, and be instructed not to take an extra dose at their next dosing interval if they previously miss a dose.

Interventions

Dimethyl fumarate

Dimethyl fumarate capsules will be dispensed during routine study appointments. 120 mg tablets will be dispensed to facilitate dose titrations. Drug will be dispensed in 1 month supply, so that compliance can be reconciled at monthly follow-up visits, and recorded in accountability logs. Participants will be instructed to take the medication with food, in the morning and at dinnertime. If participants miss a dose, they will be instructed to resume their normal dose at the next scheduled time, and be instructed not to take an extra dose at their next dosing interval if they previously miss a dose.

Intervention Type: DRUG

Placebo

Placebo capsules will be dispensed during routine study appointments. Placebo will be dispensed in 1 month supply, so that compliance can be reconciled at monthly follow-up visits, and recorded in accountability logs. Participants will be instructed to take the placebo with food, in the morning and at dinnertime. If participants miss a dose, they will be instructed to resume their normal dose at the next scheduled time, and be instructed not to take an extra dose at their next dosing interval if they previously miss a dose.

Intervention Type: DRUG

Other Intervention Names

Tecfidera

Eligibility Criteria

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. Participants with a history of active, serious or persistent infections.

12. Participants 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. Participants 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Tiffany J. Braley, MD, MS

Assistant Professor, Department of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tiffany J. Braley, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

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Other Identifiers

HUM00080121

Identifier Type: -

Identifier Source: org_study_id