AzTrials
AzTrials

Multiple SclerosisNCT02544373

CPAP to Treat Cognitive Dysfunction in MS

A study testing PAP therapy in people with Multiple Sclerosis, run by University of Michigan at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The objectives of this study are to determine the effects of obstructive sleep apnea (OSA) on cognitive function in patients with multiple sclerosis (MS); and to evaluate whether OSA treatment with positive airway pressure therapy could improve cognitive dysfunction in MS patients who have OSA. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
PAP therapy
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
135 participants
Where
1 siteUnited States
Study dates
12 Nov 2015to 25 Jun 2021
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age of 18-70 years at screening
  • Diagnosis of clinically definite MS
  • Willingness to undergo in-lab baseline polysomnography (PSG) and positive airway pressure (PAP) titration (if needed)
  • Willingness to undergo 2 separate 90-minute cognitive testing sessions
  • Either one of the following:
  • Score of >=2 sleep apnea risk factors on the "STOP-Bang" sleep apnea screening questionnaire. The STOP-Bang questionnaire is a screening tool consisting of eight items which reflect OSA risk factors. STOP-Bang scores of ≥3 indicate elevated risk for moderate-severe OSA in the general population, and scores as low as 2 are frequently seen in MS patients with OSA, based on previous data from the PI).
Show all 9Show fewer
  • OR
  • Have a pre-existing diagnosis of OSA based on a previous overnight sleep study (either home study or in-lab) but have not yet started using PAP therapy on a compliant basis. If OSA was NOT diagnosed by a U-M in-lab sleep study within the past year prior to screening, subjects must be willing to get new baseline in-lab U-M PSG as part of study.
  • Willingness to start treatment with PAP if OSA present

Who cannot join

  • Physical, psychiatric or cognitive impairment that prevents informed consent, PSG, PAP use, or reliable longitudinal follow-up
  • Cardiopulmonary conditions that may increase sleep apnea risk
  • Current treatment, such as PAP, for obstructive or central sleep apnea
  • History of surgical treatment for OSA
  • Nervous system diseases other than MS that may predispose subjects to OSA (such as Parkinson's disease, amyotrophic lateral sclerosis, or recent stroke)
  • History of concomitant central nervous system disease that could influence cognition, such as large vessel territory stroke, Alzheimer's disease, Parkinson's disease, or Lewy body dementia
Show all 16Show fewer
  • Concomitant systemic autoimmune disease with secondary central nervous system involvement (including CNS lupus or neurosarcoidosis).
  • Pregnancy
  • Evidence of clinical MS relapse within the last 30 days prior to enrollment
  • Systemic high dose steroid use (1 gram IV methylprednisolone daily for 3-5 days or equivalent)for an MS relapse within the last 30 days prior to enrollment
  • Unwillingness to initiate PAP therapy if clinically indicated
  • Severe depression at screening per the Patient Health Questionnaire-8 (PHQ-8) (The PHQ-8 is a brief, self-administered questionnaire that evaluates core symptoms associated with major depressive disorder. Scores range from 0 to 24 based on the frequency and severity of depressive symptoms over the previous two weeks.)
  • Anticipated initiation, dosage change, or discontinuation in medications that could, per the opinion of the investigators, influence cognitive test scores from baseline to follow-up, including MS disease modifying therapies, hypnotic agents, narcotic-based medications, benzodiazepines, antispasmodics, or 4-aminopyridine
  • ESS scores >= 16 on baseline visit
  • Subjects with extreme OSA accompanied by signs of cardiopulmonary compromise (RDI>60 respiratory events per hour with severe nocturnal hypoxia or unstable ECG rhythms on PSG), will be excluded unless they are randomized to immediate PAP arm
  • Any other condition or treatment that in the opinion of the investigator could affect subject safety or study eligibility

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

Other trials in United States

About this study

Official title: A Randomized Trial of Positive Airway Pressure Therapy to Treat Cognitive Dysfunction in MS Patients With Obstructive Sleep Apnea

The objectives of this study are to determine the effects of obstructive sleep apnea (OSA) on cognitive function in patients with multiple sclerosis (MS); and to evaluate whether OSA treatment with positive airway pressure therapy could improve cognitive dysfunction in MS patients who have OSA.

Read the detailed description

Up to 70% of patients with MS suffer from cognitive dysfunction (difficulties with thinking, information processing, verbal expression, or memory). Cognitive dysfunction is one of the most disabling symptoms of MS, that can profoundly affect job performance, family responsibilities, and quality of life. While no treatments have been shown to improve cognitive dysfunction in MS, many patients have not been evaluated or treated for other common health problems that could be contributing to their cognitive dysfunction.

Up to 50% of MS patients also suffer from obstructive sleep apnea (OSA). Obstructive sleep apnea is a common disorder in which the upper airway collapses during sleep, causing poor sleep quality and decreased oxygen levels in the blood. In patients without MS, OSA is a well-established cause of poor cognitive performance. Recent studies of non-MS patients also suggest that cognitive performance may improve with OSA treatment. Yet, despite the high number of MS patients with OSA, the relationship between OSA and cognitive performance, and the effects of OSA treatment on cognitive performance in MS, has not received sufficient study.

The objectives of this study are to determine the effects of obstructive sleep apnea (OSA) on cognitive function in patients with multiple sclerosis (MS); and to evaluate whether OSA treatment with positive airway pressure therapy could improve cognitive dysfunction in MS patients who also have OSA.

Interested participants with MS who screen positive on a commonly used screening tool used to detect those at high risk for OSA will be invited to participate. Consenting participants will have a baseline cognitive (memory and thinking) test to assess their cognitive function, and an overnight sleep study (polysomnogram, or PSG) to determine if they have obstructive sleep apnea. If the sleep study shows signs of sleep apnea, participants will be assigned treatment for their sleep apnea with positive airway pressure (PAP) therapy, either immediately (Group 1), or 3 months after the baseline sleep study (Group 2). Groups will be assigned at random (like flipping a coin). There is a 2/3 chance that participants will be assigned to Group 1. PAP therapy is considered standard clinical care for OSA. It involves wearing an apparatus that includes a hose and a mask (that covers the nose, or nose and mouth), connected to a small machine that blows air into the airway during sleep. In order to determine which airway pressure most effectively treats an individual's sleep apnea, and what type of mask is needed, a separate sleep study known as an overnight "PAP titration study" will also be performed. This study is similar to a PSG but also involves fitting of various masks which are then hooked up to the individual and PAP machine to test the effectiveness of various PAP settings, and to determine which mask is most tolerable for the individual.

Participants will also receive repeat cognitive testing at 3 months to see if the immediate sleep apnea treatment group (Group 1) shows improvements memory and thinking, as compared to the standard care treatment group (Group 2), who will not start apnea treatment until after their repeat cognitive test. Participants will be compensated for their travel and time throughout the course of the study.

Being tested
PAP therapy
Keywords
OSA, Obstructive Sleep Apnea, Cognition, Cognitive Dysfunction, Memory, Positive Aiway Pressure, CPAP, MS
Medical subject headings
Multiple Sclerosis, Sleep Apnea, Obstructive, Cognitive Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PAP therapyDevice

    Also called Positive airway pressure, CPAP, BiPAP, Continuous positive airway pressure

    Positive airway pressure treatment for obstructive sleep apnea

Study groups in NCT02544373
Study groupRoleWhat they receive
Immediate PAP therapy (Group 1)Active comparatorSubjects will receive PAP treatment for OSA as soon as possible after baseline PSG and repeat baseline cognitive testing 3 months after initiation of PAP therapy. PAP therapy is considered standard clinical care for OSA. It involves wearing an apparatus that includes a hose and a mask (that covers the nose, or nose and mouth), connected to a small machine that blows air into the airway during sleep. The degree of air pressure given depends on your apnea severity, and the supplied air pressure can be continuous or change with your breathing pattern (bilevel).
Receives: Device: PAP therapy
Standard Care PAP therapy (Group 2)OtherSubjects will delay PAP treatment for 3 months following their baseline sleep study, and repeat their baseline cognitive testing prior to PAP treatment for sleep apnea. PAP therapy is considered standard clinical care for OSA. It involves wearing an apparatus that includes a hose and a mask (that covers the nose, or nose and mouth), connected to a small machine that blows air into the airway during sleep. The degree of air pressure given depends on your apnea severity, and the supplied air pressure can be continuous or change with your breathing pattern (bilevel).
Receives: Device: PAP therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Association Between Obstructive Sleep Apnea (OSA) Severity [as Measured by Apnea Hypopnea Index (AHI) e.g., Number of Apneic Events Per Hour of Sleep] and Baseline Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)

    Bivariate associations between AHI measured with PSG, and baseline MACFIMS test results which include:

    • Controlled Oral Word Association Test (COWAT): verbal fluency;
    • Judgement of Line Orientation test (JLO): visuospatial perception;
    • Brief Visuospatial Memory Test Revised Total (BVMT-R Total) and Brief Visuospatial Memory Test Revised Delayed (BVMT-R Delayed): visual memory \& learning;
    • California Verbal Learning Test-II Total score (CVLT-II): verbal memory \& learning;
    • Paced Auditory Serial Addition Test-2 (PASAT-2), Paced Auditory Serial Addition Test-3 (PASAT-3) and Symbol Digit Modalities test (SDMT): memory, attention, processing speed.

    For each test higher scores indicate better cognitive performance. Beta coefficients were generated with multiple linear regression models, yielding the confidence intervals shown below.

    Measured: Participants had up to 3 weeks to complete both baseline cognitive testing and PSG

  2. Change From Baseline in Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)

    Mean change in scores on individual MACFIMS tests from baseline to month 3 cognitive testing, as calculated by Month 3 minus baseline score shown by treatment group. MACFIMS tests with score ranges (minimum-maximum) are listed here:

    • Controlled Oral Word Association Test (COWAT) 0 - no recognized upper limit;
    • Judgement of Line Orientation test (JLO) 0-34 based on scores adjusted for age and sex;
    • Brief Visuospatial Memory Test Revised Total (BVMT-R Total) 0-36;
    • Brief Visuospatial Memory Test Revised Delayed (BVMT-R Delayed), 0-12;
    • California Verbal Learning Test-II Total score (CVLT-II); (T scores necessary for analysis; 50=population mean; 10=SD);
    • Paced Auditory Serial Addition Test-2 (PASAT-2), 0-60;
    • Paced Auditory Serial Addition Test-3 (PASAT-3) 0-60; and
    • Symbol Digit Modalities test (SDMT) 0-110. For all measures, higher scores mean better performance, so based on subtracting 3 month values minus baseline, any positive numbers indicate improvement.

    Measured: baseline, 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Sep 2015 (estimated)
  2. Study start12 Nov 2015
  3. Primary completion25 Jun 2021
  4. Study completion25 Jun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
135 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02544373
Sponsor's protocol ID
HUM00098738
Status last verified
Aug 2022
First submitted
26 May 2015
Last updated
14 Sep 2022
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes

Publications

  • Brassington JC, Marsh NV. Neuropsychological aspects of multiple sclerosis. Neuropsychol Rev. 1998 Jun;8(2):43-77. doi: 10.1023/a:1025621700003.

    PubMed 9658410

  • Diamond BJ, DeLuca J, Kim H, Kelley SM. The question of disproportionate impairments in visual and auditory information processing in multiple sclerosis. J Clin Exp Neuropsychol. 1997 Feb;19(1):34-42. doi: 10.1080/01688639708403834.

    PubMed 9071639

  • DeLuca J, Barbieri-Berger S, Johnson SK. The nature of memory impairments in multiple sclerosis: acquisition versus retrieval. J Clin Exp Neuropsychol. 1994 Apr;16(2):183-9. doi: 10.1080/01688639408402629.

    PubMed 8021305

  • Kujala P, Portin R, Ruutiainen J. Memory deficits and early cognitive deterioration in MS. Acta Neurol Scand. 1996 May;93(5):329-35. doi: 10.1111/j.1600-0404.1996.tb00005.x.

    PubMed 8800343

  • Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology. 1991 May;41(5):685-91. doi: 10.1212/wnl.41.5.685.

    PubMed 2027484

  • Peyser JM, Rao SM, LaRocca NG, Kaplan E. Guidelines for neuropsychological research in multiple sclerosis. Arch Neurol. 1990 Jan;47(1):94-7. doi: 10.1001/archneur.1990.00530010120030.

    PubMed 2403789

  • Beatty WW, Paul RH, Wilbanks SL, Hames KA, Blanco CR, Goodkin DE. Identifying multiple sclerosis patients with mild or global cognitive impairment using the Screening Examination for Cognitive Impairment (SEFCI). Neurology. 1995 Apr;45(4):718-23. doi: 10.1212/wnl.45.4.718.

    PubMed 7723961

  • Knight RG, Devereux RC, Godfrey HP. Psychosocial consequences of caring for a spouse with multiple sclerosis. J Clin Exp Neuropsychol. 1997 Feb;19(1):7-19. doi: 10.1080/01688639708403832.

    PubMed 9071637

  • Rao SM, Leo GJ, Ellington L, Nauertz T, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology. 1991 May;41(5):692-6. doi: 10.1212/wnl.41.5.692.

    PubMed 1823781

  • O'Brien AR, Chiaravalloti N, Goverover Y, Deluca J. Evidenced-based cognitive rehabilitation for persons with multiple sclerosis: a review of the literature. Arch Phys Med Rehabil. 2008 Apr;89(4):761-9. doi: 10.1016/j.apmr.2007.10.019.

    PubMed 18374010

  • Canessa N, Castronovo V, Cappa SF, Aloia MS, Marelli S, Falini A, Alemanno F, Ferini-Strambi L. Obstructive sleep apnea: brain structural changes and neurocognitive function before and after treatment. Am J Respir Crit Care Med. 2011 May 15;183(10):1419-26. doi: 10.1164/rccm.201005-0693OC. Epub 2010 Oct 29.

    PubMed 21037021

  • Benedict RH, Cookfair D, Gavett R, Gunther M, Munschauer F, Garg N, Weinstock-Guttman B. Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS). J Int Neuropsychol Soc. 2006 Jul;12(4):549-58. doi: 10.1017/s1355617706060723.

    PubMed 16981607

  • Benedict RH, Fischer JS, Archibald CJ, Arnett PA, Beatty WW, Bobholz J, Chelune GJ, Fisk JD, Langdon DW, Caruso L, Foley F, LaRocca NG, Vowels L, Weinstein A, DeLuca J, Rao SM, Munschauer F. Minimal neuropsychological assessment of MS patients: a consensus approach. Clin Neuropsychol. 2002 Aug;16(3):381-97. doi: 10.1076/clin.16.3.381.13859.

    PubMed 12607150

  • Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366.

    PubMed 21387374

  • Kroenke K, Strine TW, Spitzer RL, Williams JB, Berry JT, Mokdad AH. The PHQ-8 as a measure of current depression in the general population. J Affect Disord. 2009 Apr;114(1-3):163-73. doi: 10.1016/j.jad.2008.06.026. Epub 2008 Aug 27.

    PubMed 18752852

Questions about this trial

What is this clinical trial studying?

A study testing PAP therapy in people with Multiple Sclerosis, run by University of Michigan at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Association Between Obstructive Sleep Apnea (OSA) Severity [as Measured by Apnea Hypopnea Index (AHI) e.g., Number of Apneic Events Per Hour of Sleep] and Baseline Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS) (time frame: Participants had up to 3 weeks to complete both baseline cognitive testing and PSG). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02544373, which also lists 26 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2022; AzTrials last refreshed its copy on 29 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in