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Dimethyl Fumarate for Obstructive Sleep Apnea

Primary Purpose

Obstructive Sleep Apnea, OSA, Sleep Apnea

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Dimethyl fumarate

Placebo

About this trial

This is an interventional treatment trial for Obstructive Sleep Apnea focused on measuring Obstructive Sleep Apnea, OSA, sleep apnea, snoring, dimethyl fumarate, CPAP, continuous positive airway pressure

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age of 18-65 years at screening;
Diagnosis of OSA as confirmed by previous clinical sleep study (polysomnography, PSG);
Refusal, inability, or high reluctance to use CPAP regularly for treatment of OSA, despite medical advice;
Willingness to undergo repeat sleep study (PSG) and blood studies;
Normal immune cell counts, as evidenced by complete blood count (CBC) done at screening

Exclusion Criteria:

Regular use of CPAP within the last 2 months
Physical, psychiatric or cognitive impairment that prevents informed consent, PSG, or reliable follow-up;
Cardiac conditions that may increase sleep apnea severity (e.g., congestive heart failure or recent heart attack);
Current successful treatment for obstructive or central sleep apnea, for example by CPAP, and patient agreement to continue with that treatment;
History of surgical treatment for OSA within past 6 months, or subsequent to last PSG confirmation that OSA is present;
Active nervous system diseases that may predispose subjects to OSA;
Systemic autoimmune disease that could increase inflammation and influence apnea severity (such as rheumatoid arthritis or lupus);
Pregnancy or breastfeeding;
Use of immunotherapies or immunosuppressants, currently or within past 6 months;
Anticipated initiation or dose change in tricyclic antidepressants, selective serotonin uptake inhibitors, or related compounds;
Participants with a history of active, serious or persistent infections.
Participants with recent surgery (within 3 months prior to screening), or anticipated surgery during the length of the study.
Systemic steroid use within the last 2 months (does not include local steroid injections or intranasal steroid spray);
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;
History of a lymphoproliferative disorder (such as leukemia);
History of Multiple Myeloma
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.
Refusal to use at least one reliable method of birth control (for women of childbearing age)
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)
Participants who report previous motor vehicle accidents or near-misses presumed to be due to excessive sleepiness while driving.
Any other condition or treatment that in the opinion of the investigator could affect subject safety or study eligibility.

Sites / Locations

University of Michigan

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Dimethyl Fumarate (Tecfidera®) capsules

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Mean Change in Apnea Severity as Measured by the Respiratory Disturbance Index (RDI)

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.

Secondary Outcome Measures

Mean Change in Serum Cytokine Levels (Mean Difference of Log-transformed Values)

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.

Full Information

NCT ID

NCT02438137

First Posted

April 18, 2015

Last Updated

April 28, 2017

Sponsor

University of Michigan

1. Study Identification

Unique Protocol Identification Number

NCT02438137

Brief Title

Dimethyl Fumarate for Obstructive Sleep Apnea

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Completed

Study Start Date

May 2015 (undefined)

Primary Completion Date

April 2016 (Actual)

Study Completion Date

May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Michigan

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obstructive Sleep Apnea, OSA, Sleep Apnea

Keywords

Obstructive Sleep Apnea, OSA, sleep apnea, snoring, dimethyl fumarate, CPAP, continuous positive airway pressure

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

65 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dimethyl Fumarate (Tecfidera®) capsules

Arm Type

Active Comparator

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Dimethyl fumarate

Other Intervention Name(s)

Tecfidera

Intervention Description

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

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Mean Change in Apnea Severity as Measured by the Respiratory Disturbance Index (RDI)

Description

Time Frame

Month 0 to Month 4

Secondary Outcome Measure Information:

Title

Mean Change in Serum Cytokine Levels (Mean Difference of Log-transformed Values)

Description

Time Frame

Month 0 to Month 4

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age of 18-65 years at screening; Diagnosis of OSA as confirmed by previous clinical sleep study (polysomnography, PSG); Refusal, inability, or high reluctance to use CPAP regularly for treatment of OSA, despite medical advice; Willingness to undergo repeat sleep study (PSG) and blood studies; Normal immune cell counts, as evidenced by complete blood count (CBC) done at screening Exclusion Criteria: Regular use of CPAP within the last 2 months Physical, psychiatric or cognitive impairment that prevents informed consent, PSG, or reliable follow-up; Cardiac conditions that may increase sleep apnea severity (e.g., congestive heart failure or recent heart attack); Current successful treatment for obstructive or central sleep apnea, for example by CPAP, and patient agreement to continue with that treatment; History of surgical treatment for OSA within past 6 months, or subsequent to last PSG confirmation that OSA is present; Active nervous system diseases that may predispose subjects to OSA; Systemic autoimmune disease that could increase inflammation and influence apnea severity (such as rheumatoid arthritis or lupus); Pregnancy or breastfeeding; Use of immunotherapies or immunosuppressants, currently or within past 6 months; Anticipated initiation or dose change in tricyclic antidepressants, selective serotonin uptake inhibitors, or related compounds; Participants with a history of active, serious or persistent infections. Participants with recent surgery (within 3 months prior to screening), or anticipated surgery during the length of the study. Systemic steroid use within the last 2 months (does not include local steroid injections or intranasal steroid spray); 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; History of a lymphoproliferative disorder (such as leukemia); History of Multiple Myeloma 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. Refusal to use at least one reliable method of birth control (for women of childbearing age) 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) Participants who report previous motor vehicle accidents or near-misses presumed to be due to excessive sleepiness while driving. Any other condition or treatment that in the opinion of the investigator could affect subject safety or study eligibility.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tiffany J. Braley, MD, MS

Organizational Affiliation

University of Michigan

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Dimethyl Fumarate for Obstructive Sleep Apnea

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