Trial Outcomes & Findings for CPAP to Treat Cognitive Dysfunction in MS (NCT NCT02544373)
NCT ID: NCT02544373
Last Updated: 2022-09-14
Results Overview
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.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
135 participants
Primary outcome timeframe
Participants had up to 3 weeks to complete both baseline cognitive testing and PSG
Results posted on
2022-09-14
Participant Flow
Of 135 enrolled participants,131 received both baseline cognitive testing and polysomnography for Aim 1 (pre-intervention) analyses (outside of the interventional phase of the study. Among these 131 participants, 111 were randomized for this trial.
Participant milestones
| Measure |
Immediate PAP Therapy (Group 1)
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).
PAP therapy: Positive airway pressure treatment for obstructive sleep apnea
|
Standard Care PAP Therapy (Group 2)
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).
PAP therapy: Positive airway pressure treatment for obstructive sleep apnea
|
|---|---|---|
|
Overall Study
STARTED
|
71
|
40
|
|
Overall Study
COMPLETED
|
58
|
35
|
|
Overall Study
NOT COMPLETED
|
13
|
5
|
Reasons for withdrawal
| Measure |
Immediate PAP Therapy (Group 1)
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).
PAP therapy: Positive airway pressure treatment for obstructive sleep apnea
|
Standard Care PAP Therapy (Group 2)
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).
PAP therapy: Positive airway pressure treatment for obstructive sleep apnea
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
5
|
3
|
|
Overall Study
Withdrawal by Subject
|
8
|
2
|
Baseline Characteristics
CPAP to Treat Cognitive Dysfunction in MS
Baseline characteristics by cohort
| Measure |
Immediate PAP Therapy (Group 1)
n=71 Participants
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).
PAP therapy: Positive airway pressure treatment for obstructive sleep apnea
|
Standard Care PAP Therapy (Group 2)
n=40 Participants
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).
PAP therapy: Positive airway pressure treatment for obstructive sleep apnea
|
Total
n=111 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
48.9 years
STANDARD_DEVIATION 9 • n=5 Participants
|
49.2 years
STANDARD_DEVIATION 9.2 • n=7 Participants
|
49.0 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
50 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
78 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
61 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian/Alaskan Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown/Not reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic
|
69 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
106 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
71 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
111 Participants
n=5 Participants
|
|
Apnea Hypopnea Index
|
23.1113 units on a scale
STANDARD_DEVIATION 19.22115 • n=5 Participants
|
20.4875 units on a scale
STANDARD_DEVIATION 16.30875 • n=7 Participants
|
22.1658 units on a scale
STANDARD_DEVIATION 18.19362 • n=5 Participants
|
PRIMARY outcome
Timeframe: Participants had up to 3 weeks to complete both baseline cognitive testing and PSGPopulation: These analyses were conducted to examine associations between apnea severity and cognitive performance prior to randomization and PAP intervention. Four out of 135 consented had missing data that did not allow analysis of associations.
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.
Outcome measures
| Measure |
All Participants Prior to Randomization
n=131 Participants
All participants who received both baseline cognitive testing and diagnostic polysomnography (PSG), prior to randomization. Participants who did not have obstructive sleep apnea (OSA) on PSG concluded the study prior to randomization.
|
Standard Care PAP Therapy (Group 2)
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).
PAP therapy: Positive airway pressure treatment for obstructive sleep apnea
|
|---|---|---|
|
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)
COWAT
|
-0.014 beta coefficient
Interval -0.126 to 0.099
|
—
|
|
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)
JLO
|
-0.003 beta coefficient
Interval -0.044 to 0.037
|
—
|
|
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)
BVMT-R Total
|
-0.061 beta coefficient
Interval -0.124 to 0.001
|
—
|
|
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)
BVMT-R Delayed
|
-0.026 beta coefficient
Interval -0.051 to -0.001
|
—
|
|
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)
CVLT-II Total
|
0.009 beta coefficient
Interval -0.117 to 0.135
|
—
|
|
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)
PASAT-2 Total
|
-0.022 beta coefficient
Interval -0.13 to 0.086
|
—
|
|
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)
PASAT-3 Total
|
-0.061 beta coefficient
Interval -0.189 to 0.067
|
—
|
|
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)
SDMT
|
-0.137 beta coefficient
Interval -0.268 to -0.007
|
—
|
PRIMARY outcome
Timeframe: baseline, 3 monthsPopulation: includes participants who had MACFIMS testing at both timepoints (baseline and month 3)
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.
Outcome measures
| Measure |
All Participants Prior to Randomization
n=71 Participants
All participants who received both baseline cognitive testing and diagnostic polysomnography (PSG), prior to randomization. Participants who did not have obstructive sleep apnea (OSA) on PSG concluded the study prior to randomization.
|
Standard Care PAP Therapy (Group 2)
n=40 Participants
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).
PAP therapy: Positive airway pressure treatment for obstructive sleep apnea
|
|---|---|---|
|
Change From Baseline in Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)
COWAT
|
2.5 score
Standard Deviation 8.23
|
2.69 score
Standard Deviation 8.35
|
|
Change From Baseline in Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)
JLO
|
0.28 score
Standard Deviation 2.78
|
0.60 score
Standard Deviation 3.39
|
|
Change From Baseline in Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)
BVMT-R Total
|
1.81 score
Standard Deviation 5.04
|
1.43 score
Standard Deviation 4.99
|
|
Change From Baseline in Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)
BVMT-R Delayed
|
0.95 score
Standard Deviation 1.99
|
0.54 score
Standard Deviation 1.88
|
|
Change From Baseline in Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)
CVLT-II
|
2.84 score
Standard Deviation 9.59
|
4.77 score
Standard Deviation 8.88
|
|
Change From Baseline in Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)
PASAT-2
|
2.27 score
Standard Deviation 6.95
|
2.09 score
Standard Deviation 5.14
|
|
Change From Baseline in Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)
PASAT-3
|
0.61 score
Standard Deviation 7.16
|
2.53 score
Standard Deviation 8.33
|
|
Change From Baseline in Performance on the Minimal Assessment of Cognitive Function in MS Battery (MACFIMS)
SDMT
|
0.16 score
Standard Deviation 6.24
|
1.03 score
Standard Deviation 6.72
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 weeksOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 weeksOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 weeksOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 weeksOutcome measures
Outcome data not reported
Adverse Events
Immediate PAP Therapy (Group 1)
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Standard Care PAP Therapy (Group 2)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Immediate PAP Therapy (Group 1)
n=71 participants at risk
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).
PAP therapy: Positive airway pressure treatment for obstructive sleep apnea
|
Standard Care PAP Therapy (Group 2)
n=40 participants at risk
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).
PAP therapy: Positive airway pressure treatment for obstructive sleep apnea
|
|---|---|---|
|
Infections and infestations
Common cold
|
8.5%
6/71 • AE data were collected from the time participants were randomized until 30 days after the treatment period (per protocol = 3 month treatment period + 30 day post-treatment = 4 months).
|
0.00%
0/40 • AE data were collected from the time participants were randomized until 30 days after the treatment period (per protocol = 3 month treatment period + 30 day post-treatment = 4 months).
|
|
Respiratory, thoracic and mediastinal disorders
Congestion
|
8.5%
6/71 • AE data were collected from the time participants were randomized until 30 days after the treatment period (per protocol = 3 month treatment period + 30 day post-treatment = 4 months).
|
0.00%
0/40 • AE data were collected from the time participants were randomized until 30 days after the treatment period (per protocol = 3 month treatment period + 30 day post-treatment = 4 months).
|
Additional Information
Tiffany J. Braley, MD, MS, Associate Professor of Neurology
University of Michigan
Phone: 734-936-6267
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place