Yoga-based, Noninvasive Glymphatic Clearance Augmentation in Alzheimer's Disease.
- Conditions
- Alzheimer DiseaseMild Cognitive Impairment (MCI)
- Registration Number
- NCT06989242
- Lead Sponsor
- CIATRIX, INC.
- Brief Summary
This clinical trial evaluates a yoga-based intervention delivered through a powered therapeutic device designed to guide breathing and body movements. Building on evidence that mind-body practices may promote healthy aging, cognitive function, and glymphatic flow, the study uses physiological measurements, including fNIRS and wearable sensors, to investigate mechanisms and potential benefits in individuals at risk for Alzheimer's disease.
- Detailed Description
Brief Summary:
The current trial builds on recent findings that highlight the effectiveness of mind-body interventions, such as yoga and deep abdominal breathing, in promoting healthy aging and slowing cognitive decline. Research suggests that yoga and body-mind practices can improve well-being and reduce biological markers of aging in both healthy older adults and those at risk for dementia. Yogic breathing and body movements may enhance cerebrospinal fluid (CSF) flow as an important component of the glymphatic function. The trial employs physiological measurements, including fNIRS and wearable sensors, to investigate the mechanisms and clinical benefits of yoga-based interventions for AD.
The primary objective is to assess the safety, tolerability, feasibility of a 4-week Fluere™ therapy protocol for stage 3 and 4 AD patients.
The secondary objectives focus on clinical effectiveness related to:
1. Body posture improvement
2. Changes in HRV (reflecting the stress level and quality of sleep)
Although the duration of the study is short, and the study is not powered to detect changes in biomarkers or clinical efficacy, secondary endpoints will be analyzed to assess trends in improvement from baseline.
Additional secondary outcomes will focus on biomarker proxies of glymphatic clearance:
1. Impact on digital biomarkers (neuro-fluid dynamics (hemodynamics, CSF) and redox state of cytochrome-c-oxidase activity using fNIRS)
2. Effect on plasma biomarkers associated with neurodegeneration, inflammation and neural plasticity - GFAP, NfL and S100B and BDNF
3. Cognitive (spatial memory) and functional outcomes
4. Sleep patterns and quality through wearable devices and questionnaires
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 60
- 55-85 years of age
- Current diagnostic criteria for stage 3 AD patients (AD-MCI)
- Current diagnostic criteria for stage 4 AD patients (mAD)
- Able to provide consent to be in the study
- Willing and able to participate in study activities
- Able to lay supine for 30-45 minutes
- Able to walk 20 meters
- Willing to not perform additional mind-body practices during the duration of the study
- Able to use a wearable electronic device (Smart watch)
- Inability to provide informed consent
- Regular use of muscle relaxants or anti-anxiety drugs
- Any muscle or skeletal issues that would make it difficult to lie still in the supine position for the 1-hour physical therapy
- Craniospinal disorders, e.g., Chiari Malformation.
- Spinal injuries, clinically relevant disc herniation, spinal stenosis, spondylolisthesis in the sacral, lumbar, thoracic, or cervical spine, spinal bifida, Recent Spinal Surgery
- Severe osteoporosis with a risk of fracture
- History of neurological disorders such as stroke (during the last year before study start), mild brain injury within past 6 months, multiple sclerosis, presence of intracranial hemorrhage, hydrocephalus, meningitis, encephalitis, brain tumor (except of asymptomatic meningioma GI)
- Serious sleep disorders - narcolepsy
- Major or uncontrolled psychiatric illness or major depression.
- Any condition requiring the use of medication that acts on the brain such as stimulants, sedatives (hypnotics and benzodiazepines), antipsychotics, and anti-anxiety medications, (we will include patients with stable antidepressant treatment and being on mild anti-seizure medication due to polyneuropathy)
- Active infection or uncontrolled significant systemic illnesses
- Asthma, chronic obstructive pulmonary disease
- Recent hearth attack, Implantable defibrillator, poorly controlled blood pressure cardiac arrhythmia, unstable angina pectoris, or symptomatic congestive heart failure
- People at risk of blood clots or deep vein thrombosis (DVT) might want to avoid prolonged sitting in the chair
- Obesity over 135 kg (300lb)
- Smoking more than 5 cigarettes a day or drinking more than 1 alcoholic beverage a day
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Number and type of intervention-related adverse events as assessed by a yoga-specific adverse events questionnaire Throughout the 4-week intervention period Safety will be evaluated using a standardized yoga-specific adverse events questionnaire administered after each session. Adverse events will be recorded, categorized (e.g., musculoskeletal, autonomic, psychological), and summarized by frequency and severity. Only events judged as related to the intervention will be included.
Number of participants completing ≥90% of scheduled intervention sessions 4 weeks (intervention period) Feasibility of the intervention will be assessed by the number of participants who attend at least 90% of scheduled sessions (i.e., ≥11 out of 12 sessions). Reported as count and percentage of total enrolled participants.
Mean percentage of completed intervention sessions per participant 4 weeks (intervention period) Calculated as the average percentage of completed sessions per participant across the study population. This reflects session adherence at the group level.
Number of participants who withdraw from the study before completing intervention 4 weeks (intervention period) The dropout rate will be determined by the number of participants who discontinue the study before completing all planned sessions, regardless of reason.
- Secondary Outcome Measures
Name Time Method Change in global cognitive function as measured by the Mini-Mental State Examination (MMSE) Baseline and at Week 4 Global cognitive function will be assessed using the MMSE. This brief screening tool evaluates orientation, memory, attention, language, and visuospatial skills.
Change in functional ability as measured by the Functional Activities Questionnaire (FAQ-CZ) Baseline and at Week 4 Functional status will be assessed using the Czech version of the FAQ-CZ, which evaluates the participant's ability to perform instrumental activities of daily living. Higher scores indicate greater functional impairment. Score (range 0-30; higher = more impairment)
Change in Heart Rate Variability During Therapy over time During each session across 4 weeks HRV is measured during device-guided breathing and movement sessions using wearable sensors.
Plasma Biomarkers of Neurodegeneration and Inflammation Baseline and Week 4 Changes in blood-based biomarkers associated with neurodegeneration and inflammation, including neurofilament light chain (NfL), brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein B (S100B)
Change in vertical postural alignment as measured by digital posture analysis Baseline and 4 timepoints altogether corresponding to 4 treatment weeks Posture will be quantified using photographic images captured weekly, with a standardized posture grid overlaid on each image. The grid will allow for objective measurement of spinal alignment and the sagittal vertical axis.
Change in spine flexibility as measured by the Thomayer test (in cm) Baseline and weekly Spine flexibility will be assessed using the Thomayer forward bend test. Participants reach toward the floor from a standing position with knees straight, and the distance between fingertips and floor (positive or negative) will be recorded and compared pre/post.
Change in nightly average heart rate variability (SMSSD) during sleep as measured by wearable sensors in Milliseconds (ms) Nightly, throughout the 4-week study period HRV will be continuously monitored using validated wearable PPG-based devices. The nightly average root mean square of successive differences (RMSSD) will be extracted and averaged weekly. Baseline-week values will be compared to Week 4 values.
Change in nightly average resting heart rate during sleep as measured by wearable sensors (in bpm) Nightly, throughout the 4-week study period Resting heart rate will be measured each night using wearable devices during sleep. Weekly averages will be calculated and compared from baseline to Week 4.
Change in nightly average respiratory rate (Breaths per minute) during sleep as measured by wearable sensors Nightly, throughout the 4-week study period Respiratory rate will be assessed via wearable sensors each night during sleep. Weekly averages will be calculated and compared between baseline and the end of the intervention.
Change in cortical hemodynamic activity (HbO and HbR concentrations) at rest and during intervention, measured by fNIRS Baseline, Week 4, and during each intervention session Hemodynamic changes will be assessed using fNIRS to measure oxygenated (HbO) and deoxygenated hemoglobin (HbR) concentrations in the prefrontal cortex.
Change in cortical water signal (tissue hydrodynamics) measured by H2O-specific wavelength sensor Baseline, Week 4, and during each intervention session Hydrodynamic properties of cortical tissue will be assessed using NIR absorption at water-sensitive wavelengths (e.g., \~980 nm). Water content changes will be used as a proxy for CSF bulk flow / interstitial flow.
Change in oxidation state of cytochrome c oxidase measured by broadband fNIRS Baseline, Week 4, and during each intervention session Redox activity of mitochondrial cytochrome c oxidase (oxCCO) will be evaluated using broadband fNIRS to assess metabolic shifts in the prefrontal cortex.
Change in nightly sleep stage distribution as measured by PPG-based wearable sensors - Percentage of total sleep time in each of the sleep stages Nightly, over the 4-week intervention period Sleep architecture will be measured using photoplethysmography-based wearable devices each night. Proportions of time spent in light, deep, and REM sleep will be computed and averaged weekly.
Change in subjective sleep quality score as measured by the GlymphActive Questionnaire (includes PSQI) Baseline and Week 4 Subjective sleep quality will be assessed using the GlymphActive Questionnaire, a composite tool incorporating the Pittsburgh Sleep Quality Index (PSQI).
Change in spatial navigation performance (corrent responses) as measured by the Intersections Spatial Memory Cognitive Task Familiarization at screening, Baseline and Week 4 The Intersections Task is a 3D computerized spatial navigation test mimicking real-city routes. It assesses egocentric and allocentric spatial memory and perspective-taking. Participants are transported across intersections during the learning phase and later asked to recall correct routes.
Change in subjective memory complaints as measured by the McNair Memory Complaint Questionnaire Baseline and Week 4 Subjective memory will be evaluated using the McNair Memory Complaint Questionnaire. It assesses frequency and severity of self-perceived memory problems in daily life. Higher scores reflect more frequent complaints.
Change in anxiety symptoms as measured by the Beck Anxiety Inventory (BAI) Baseline and Week 4 Anxiety symptoms will be measured using the Beck BAI, a 21-item self-report scale assessing the severity of anxiety symptoms. Higher scores indicate greater anxiety severity.
Change in depressive symptoms as measured by the Geriatric Depression Scale - Short Form (GDS-15) Baseline and Week 4 Depressive symptoms will be assessed using the GDS-15. Participants respond yes/no to items related to mood and functioning. Higher scores indicate more depressive symptoms.
Change in Global QoL score as measured by the WHOQOL-BREF Baseline and Week 4 Global quality of life and general health will be assessed using the first two items of the WHOQOL-BREF questionnaire. Participants rate their overall quality of life and satisfaction with health. Scores are averaged and transformed to a 0-100 scale. Higher scores indicate better perceived overall well-being and health.
Change in plasma neurofilament light chain (NfL) concentration Baseline and Week 4 NF-L, a marker of axonal damage, will be measured in plasma samples using an ultrasensitive immunoassay.
Change in plasma BDNF concentration Baseline and Week 4 BDNF, a neurotrophin associated with synaptic plasticity and neuroprotection, will be quantified in plasma. Using Simoa technology.
Change in plasma glial fibrillary acidic protein (GFAP) concentration Baseline and Week 4 GFAP, a biomarker of astrocytic activation and gliosis, will be measured in plasma using immunoassay-based techniques. Pre vs. post-intervention changes will be analyzed.
Change in plasma S100 calcium-binding protein B (S100B) concentration Baseline and Week 4 S100B, a marker of blood-brain barrier disruption and glial activity, will be measured in plasma using ELISA technology.
Trial Locations
- Locations (3)
Neuro Health Centrum S.R.O
🇨🇿Brno, Czechia
Neuropsychiatrie s.r.o., Terronska 580/19
🇨🇿Prague, Czechia
AuraMedica s.r.o., Neurologická ambulancia, OMNIA BUSINESS CENTER, Tomášikova 19081/28C
🇸🇰Bratislava, Slovakia