Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06467682 |
| Other study ID # |
EEBK/EP 2023/60 |
| Secondary ID |
101034403 |
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 2024 |
| Est. completion date |
May 2025 |
Study information
| Verified date |
June 2024 |
| Source |
University of Cyprus |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Obstructive sleep apnea (OSA) contributes to a number of adverse health effects, particularly
on brain health. Chronic sleep disturbances caused by OSA could adversely affect cognitive
health. Exercise is recommended as a non-pharmacological intervention for patients who are
intolerant to continuous positive airway pressure (CPAP) and has been shown to have
beneficial effects on brain health and cognitive function. The aim of this protocol is to
investigate the effects of a 12-week tele-exercise program on cognitive function and specific
parameters of brain activity, including brain metabolism and oxygenation, in patients with
OSA. The project aims to demonstrate the multi-dimensional relationship between exercise,
cognition and brain oxygenation/metabolism. Our local ethics committee has approved the
study. Our population sample (group A = OSA with cognitive impairment (CI) and tele-exercise;
group B = OSA with CI and no tele-exercise; group C = OSA without CI and no tele-exercise)
will undergo assessment both before and after a 12-week tele-exercise intervention program.
This assessment will include a comprehensive battery of subjective and objective assessment
tests. Data will be analysed according to group stratification. We hypothesize a beneficial
effect of tele-exercise on sleep and cognitive parameters and we are confident that this
study will raise awareness among healthcare professionals of the brain health benefits of
exercise in patients with low compliance to CPAP treatment.
Description:
Background: Obstructive sleep apnea (OSA) is characterized by repetitive episodes of
obstruction of the upper airway during sleep and leads to intermittent hypoxia, sleep
fragmentation, hypercapnia and sympathetic hyperactivity which are associated with multiple
adverse effects on health, in particular with brain health. Hyperarousability in OSA has a
negative impact on sleep in the macro- and micro-architecture and sleep continuity, both of
which are important players in neurogenesis, brain plasticity, alertness, and memory
formation and consolidation. Thus, chronic sleep changes caused by OSA could negatively
affect cognitive health. Both sleep fragmentation and intermittent hypoxia interfere with
brain structure and function, increasing their vulnerability to neurodegenerative diseases.
The prevalence of OSA is increasing as it is conjoined with obesity and it tends to elude
clinicians' attention, as in only 10% of the population the definitive diagnosis can be
established. Almost 80% of OSA patients report declining performance at work while 40% of
dementia risk is attributable to modifiable risk factors such as physical inactivity.
Exercise offers a wide variety of benefits for the general population as it improves the
cardiopulmonary, and metabolic profile. In addition, exercise is recommended as a low-cost,
easily administered, and non-pharmacologic intervention, with positive effect on brain health
and cognitive function, mainly by improving the sleep architecture, by enhancing the
neurovascular oxygenation process and cerebral oxygenation, by reducing sympathetic
overactivity and improving vascular function at rest and during exercise or mental stress.
Finally, it has been shown that exercise can counteract the many aspects of decline in the
brain's environment, such as the reduced blood flow and the lack of important factors (i.e.
brain-derived neurotrophic factor-BDNF) that nurture brain neurons and encourage the growth
and development of new neurons and synapses.
Therefore, long-term exercise providing the greatest and longest-lasting benefits e.g.
increase cerebral neurovascular dynamics as assessed with functional Near-Infrared
Spectroscopy (fNIRS) method and the intensity of exercise being related to cognitive
functions such as improve memory after 12-week aerobic exercise and exercise with
resistances. The effectiveness of different physical activity programs has not been properly
established and some studies suggest that supervised versus self-selected programs might have
similar results. In addition, the types of exercise programs in patients with sleep disorders
have been addressed in literature. However, it has been noted that compliance in supervised
programs in particular those lasting several weeks can often be an important limitation of
the studies. Tele-exercising could be a key to overcome this important limitation, however,
data on tele-exercising seems to be scarce.
Purpose: The main goal of the study is to explore the impact of a 12-week tele-exercising
program on the cognitive profile as well as on specific parameters of brain functions, brain
metabolism and brain oxygenation in patients with obstructive sleep apnea, thus highlighting
the multidimensional relationship between physical exercise, cognition and brain
oxygenation/metabolism. We will therefore apply a 12-week, wearable-track, tele-exercise
intervention in patients with a Sleep Apnea Syndrome with and without cognitive impairment
and compare the groups outcome on cognition and brain metabolism.
The primary aim of this study is to investigate the extent to which tele-exercise improves
cognitive functions in patients with OSA.
For this aim, we will compare the cognitive performance at baseline and at 12-weeks follow-up
in 3 groups of patients.
1. Patients with OSA without cognitive impairment
2. Patients with cognitive impairment assigned to a 12-week tele-exercising program
3. Patients with cognitive impairment not assigned to a tele-exercising intervention
For the screening of cognitive impairment and the evaluation of cognitive outcome, the
following cognitive tests will be performed:
- Attention/orientation, memory, verbal fluency, language and visuospatial abilities at
ADDENBROOKE'S COGNITIVE EXAMINATION - ACE-R.
- Outcome: Changes between baseline and follow-up at ACE-R subdomains' scores
- Executive function and rote memory
- Outcome: Score at Trail Making Test A and B (TMT)
- Verbal episodic memory based on subdomains of encoding process and immediate recall,
free and cued recall, recognition and delayed recall
- Outcome: Score in a serial verbal learning task, with control of encoding and recall,
according to the modified procedure of Grober and Buschke
- Procedural memory:
- Outcome: performance in a variation of the visual-motor skill-learning task the Mirror
Tracing Task (MTT)
- Working memory with subdomains the auditory information processing speed, flexibility
and working memory span:
- Outcome: performance in the Modified Paced Auditory Serial Addition Test (PASAT) and in
a task for "Transformed Auditory Span".
The secondary aims of this study are:
1. To investigate the extent to which tele-exercise has a positive impact on brain
oxygenation and metabolism in patients with OSA.
Outcome: cerebral oxygenation according to fNIRS-based measure levels of oxy-hemoglobin
(HbO) and deoxygenated-hemoglobin (deoxy-Hb) For this aim, we will compare cerebral
oxygenation values fNIRS- at baseline and following a 12-week follow-up in the, above
mentioned, three groups of patients.
2. Investigate the extent to which tele-exercise has a positive impact on sleep
architecture in patients with OSA.
For this aim, we will compare polysomnography quantitative and qualitative parameters as well
as scores in sleep/wake questionnaires at baseline and at 12 weeks follow-up in the, above
mentioned, three groups of patients.
Outcomes: Change in sleep architecture, sleep staging features and respiratory features in
PSG between baseline and 12-weeks follow up.
Participants: We will recruit patients with clinical suspicion of OSA from Sleep Outpatient
clinics at the Nicosia General Hospital, Cyprus, to undergo in home-based polysomnography
study with portable device [1]. We will perform a screening cognitive test (ACE-R) to
identify individuals with cognitive impairment. Patients with OSA and cognitive impairment
(CI) will be randomized to two groups: with CI that will undergo the tele-exercise program
(TEp) (Group A, N=20) and with CI That will not undergo the TEp (Group B, N=20). A third
matched group (Group C) of OSA patients without cognitive impairment (N=20) will act as
another control group and will undergo the tele-exercise program. A sample size estimation,
based on previous studies showed that 20 patients per group would be sufficient to detect
differences in our primary outcome. Groups A and C will carry out a tele-exercise program
form Unique Safe Tele-Exercise Project platform (https://ustep.gr), on a 12-week duration.
All patients which will be enrolled in our study will receive non-CPAP treatment (delayed
therapy). Α feasibility study will precede with 10 OSA patients (Apnea-Hypopnea-Index, AHI
>15 events/h) and similar characteristics, for a 12-week period of tele-exercising so as
to investigate and record data related to exercise adherence, drop-out and compliance. All
patients group they will be recommendations for diet focused on body weight loss as percent
of body fat (where required) and sleep position to improve their quality of life (scale
score).
Data collected: Study-related assessments include: a) standard lung function testing,
followed by the diffusing capacity of the lungs for carbon monoxide according to ATS/ERS
guidelines, b) physical fitness tests [6-MWT (meters) , handgrip strength test (kg) and 30s
Sit-to-Stand (repetitions)], so as to record and assess O2 consumption (mL/min/kg) and muscle
strength (kg), c) the perceptual ability and reaction time test (ms), d) prior to physical
fitness tests, will answer questionnaires on: quality and patterns of sleep (PSQI), shifting
attention and for selective attention (TMT A and Β), Epworth Sleep Scale (ESS), Karolinska
Sleepiness Scale (KSS), cognitive impairment OSA risk (MoCA), and work ability (WAI) (scales
scores) and e) assessments to record cerebral oxygenation-oxygenated (μmol/L) and
deoxygenated hemoglobin (μmol/L) (fNIRS) during physical fitness tests, reaction time and
when answering the questionnaires. All the above assessments will be performed at baseline
and at follow-up in 3 months.
Interventions program: The 12-week TEp will be performed and supported by the uStep platform,
with each patient taking part in 3 training sessions per week with a 60-min duration period
per training session. There will be personalized training sessions: a) warm-up and warm-down
(5-min respectively) with the mobility exercises and respiratory exercises for upper and
lower limbs, b) aerobic exercise (30-min) with continuous outdoor walking (intensity
calculation according HRpeak during 6MWT and self-reported feeling of dyspnea and leg
fatigue) and c) multi-joint strength exercises (20-min) to improve the strength of upper and
lower limbs (intensity calculation according to muscle strength tests). Participants of the
tele-exercise program will use wearable-based tracking, during intervention period, to
assessment the cardio-oxygenation.
