CPAP to Treat Cognitive Dysfunction in MS
A Randomized Trial of Positive Airway Pressure Therapy to Treat Cognitive Dysfunction in MS Patients With Obstructive Sleep Apnea
What it found
Results are posted in the registry, but without a statistical test of the main measure. See the numbers below.
What was tested
Treatment tested
- PAP therapy
Results by group
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)
Participants had up to 3 weeks to complete both baseline cognitive testing and PSG
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| All Participants Prior to Randomization | -0.014 beta coefficient | -0.126–0.099 | 131 |
| All Participants Prior to Randomization | -0.003 beta coefficient | -0.044–0.037 | 131 |
| All Participants Prior to Randomization | -0.061 beta coefficient | -0.124–0.001 | 131 |
| All Participants Prior to Randomization | -0.026 beta coefficient | -0.051–-0.001 | 131 |
| All Participants Prior to Randomization | 0.009 beta coefficient | -0.117–0.135 | 131 |
| All Participants Prior to Randomization | -0.022 beta coefficient | -0.13–0.086 | 131 |
| All Participants Prior to Randomization | -0.061 beta coefficient | -0.189–0.067 | 131 |
| All Participants Prior to Randomization | -0.137 beta coefficient | -0.268–-0.007 | 131 |
Change From Baseline in Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)
baseline, 3 months
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Immediate PAP Therapy (Group 1) | 2.5 score | 8.23 (Standard Deviation) | 71 |
| Standard Care PAP Therapy (Group 2) | 2.69 score | 8.35 (Standard Deviation) | 40 |
| Immediate PAP Therapy (Group 1) | 0.28 score | 2.78 (Standard Deviation) | 71 |
| Standard Care PAP Therapy (Group 2) | 0.60 score | 3.39 (Standard Deviation) | 40 |
| Immediate PAP Therapy (Group 1) | 1.81 score | 5.04 (Standard Deviation) | 71 |
| Standard Care PAP Therapy (Group 2) | 1.43 score | 4.99 (Standard Deviation) | 40 |
| Immediate PAP Therapy (Group 1) | 0.95 score | 1.99 (Standard Deviation) | 71 |
| Standard Care PAP Therapy (Group 2) | 0.54 score | 1.88 (Standard Deviation) | 40 |
| Immediate PAP Therapy (Group 1) | 2.84 score | 9.59 (Standard Deviation) | 71 |
| Standard Care PAP Therapy (Group 2) | 4.77 score | 8.88 (Standard Deviation) | 40 |
| Immediate PAP Therapy (Group 1) | 2.27 score | 6.95 (Standard Deviation) | 71 |
| Standard Care PAP Therapy (Group 2) | 2.09 score | 5.14 (Standard Deviation) | 40 |
| Immediate PAP Therapy (Group 1) | 0.61 score | 7.16 (Standard Deviation) | 71 |
| Standard Care PAP Therapy (Group 2) | 2.53 score | 8.33 (Standard Deviation) | 40 |
| Immediate PAP Therapy (Group 1) | 0.16 score | 6.24 (Standard Deviation) | 71 |
| Standard Care PAP Therapy (Group 2) | 1.03 score | 6.72 (Standard Deviation) | 40 |
Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.
Safety
| Group | Participants at risk | Serious adverse events | Deaths |
|---|---|---|---|
| Immediate PAP Therapy (Group 1) | 71 | 0 (0.0%) | 0 |
| Standard Care PAP Therapy (Group 2) | 40 | 0 (0.0%) | 0 |
As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.
What it measured
Main measures
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)
Participants had up to 3 weeks to complete both baseline cognitive testing and PSG
Thinking and memoryMood and sleepChange From Baseline in Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)
baseline, 3 months
Thinking and memory
Who could take part
MS (type not specified) · 18 to 70
Show the full criteria
Inclusion criteria
1. Age of 18-70 years at screening 2. Diagnosis of clinically definite MS 3. Willingness to undergo in-lab baseline polysomnography (PSG) and positive airway pressure (PAP) titration (if needed) 4. Willingness to undergo 2 separate 90-minute cognitive testing sessions 5. 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). 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. 6. Willingness to start treatment with PAP if OSA present
Exclusion criteria
1. Physical, psychiatric or cognitive impairment that prevents informed consent, PSG, PAP use, or reliable longitudinal follow-up 2. Cardiopulmonary conditions that may increase sleep apnea risk 3. Current treatment, such as PAP, for obstructive or central sleep apnea 4. History of surgical treatment for OSA 5. Nervous system diseases other than MS that may predispose subjects to OSA (such as Parkinson's disease, amyotrophic lateral sclerosis, or recent stroke) 6. 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 7. Concomitant systemic autoimmune disease with secondary central nervous system involvement (including CNS lupus or neurosarcoidosis). 8. Pregnancy 9. Evidence of clinical MS relapse within the last 30 days prior to enrollment 10. 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 11. Unwillingness to initiate PAP therapy if clinically indicated 12. 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.) 13. 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 14. ESS scores >= 16 on baseline visit 15. 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 16. Any other condition or treatment that in the opinion of the investigator could affect subject safety or study eligibility
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
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.
Papers
Results
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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.Background
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History
Started
Nov 2015
Main results due
Jun 2021
Finished
Jun 2021
Results posted
Sept 2022