Dimethyl Fumarate for Obstructive Sleep Apnea

April 28, 2017 updated by: Tiffany J. Braley, MD, MS, University of Michigan

A Randomized Clinical Trial of Dimethyl Fumarate as a Novel Therapeutic Agent for Obstructive Sleep Apnea

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: 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.
Other Names:
  • Tecfidera
Placebo Comparator: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change in Apnea Severity as Measured by the Respiratory Disturbance Index (RDI)
Time Frame: Month 0 to Month 4
For the 50 participants who had interpretable month 4 polysomnography (PSG) data available, mean change in sleep apnea severity, as measured by the mean change in respiratory disturbance index (RDI) between baseline (Month 0) PSG and Month 4 PSG, was calculated. The RDI represents the total number of apneas, hypopneas and respiratory-related arousals per hour of sleep.
Month 0 to Month 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change in Serum Cytokine Levels (Mean Difference of Log-transformed Values)
Time Frame: Month 0 to Month 4
Levels of markers in the blood known as cytokines (measured in picograms per milliliter) were measured on a monthly basis from Month 0 (baseline) to Month 4. The outcome is the mean difference in cytokine level from baseline to month 4 (mean level at Month 4 - mean level at Baseline). Values were log-transformed for normality, prior to analysis.
Month 0 to Month 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Investigators

  • Principal Investigator: Tiffany J. Braley, MD, MS, University of Michigan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2015

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

May 1, 2016

Study Registration Dates

First Submitted

April 18, 2015

First Submitted That Met QC Criteria

May 5, 2015

First Posted (Estimate)

May 8, 2015

Study Record Updates

Last Update Posted (Actual)

May 31, 2017

Last Update Submitted That Met QC Criteria

April 28, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HUM00080121

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Obstructive Sleep Apnea

Clinical Trials on Dimethyl fumarate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Japan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe