CPAP to Treat Cognitive Dysfunction in MS

NCT02544373 | Completed Results FDA Device

• 1 other identifier: HUM00098738
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Sclerosis

Keywords

OSA; Obstructive Sleep Apnea; Cognition; Cognitive Dysfunction; Memory; Positive Aiway Pressure; CPAP; MS

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

  baseline, 3 months

Other Outcomes (4)

• Association Between Polysomnographic Measures of Sleep Efficiency (Ratio of Time Spent Asleep to Total Time in Bed) and Baseline Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)

  3 weeks

• Association Between Wake Time After Sleep Onset (Total Time in Minutes Spent Awake After Sleep Onset, and Before Final Awakening Time) and Baseline Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)

  3 weeks

• Association Between the Total Arousal Index (Average Number of EEG Arousals Per Hour of Sleep) and Baseline Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)

  3 weeks

Study Arms (2)

Immediate PAP therapy (Group 1)

ACTIVE COMPARATOR

Subjects 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).

Device: PAP therapy

Standard Care PAP therapy (Group 2)

OTHER

Subjects 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).

Device: PAP therapy

Interventions

PAP therapy DEVICE

Positive airway pressure treatment for obstructive sleep apnea

Also known as: Positive airway pressure, CPAP, BiPAP, Continuous positive airway pressure, Bi-level positive airway pressure

Immediate PAP therapy (Group 1); Standard Care PAP therapy (Group 2)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Michigan: lead
• National Multiple Sclerosis Society: collaborator

Study Sites (1)

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (26)

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MeSH Terms

Conditions

Multiple Sclerosis; Sleep Apnea, Obstructive; Cognitive Dysfunction

Interventions

Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Results Point of Contact

• Title: Tiffany J. Braley, MD, MS, Associate Professor of Neurology
• Organization: University of Michigan

tbraley@med.umich.edu

734-936-6267

Study Officials

• Tiffany Braley, MD, MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Neurology

Study Record Dates

• First Submitted: May 26, 2015
• First Posted: September 9, 2015
• Study Start: November 12, 2015
• Primary Completion: June 25, 2021
• Study Completion: June 25, 2021
• Last Updated: September 14, 2022
• Results First Posted: September 14, 2022

Record last verified: 2022-08

Locations

US (1)