Yoga-based, Movement Therapy Device as Noninvasive Glymphatic Clearance Augmentation in Alzheimer's Disease.

Official title

Yoga-based, Movement Therapy Device as Noninvasive Glymphatic Clearance Augmentation in Alzheimer's Disease. The Feasibility and Safety Trial With Preliminary Clinical, Digital, and Fluid Biomarker Proxies of Glymphatic Clearance

Overview

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

Interventions

• Device Yoga-Based Therapeutic Device (incorporating guided breathing and movement)
  The Fluere™ Therapeutic Device is a computer-guided, electro-mechanical system designed to simulate yoga-inspired spinal movement and rhythmic breathing. Resembling a dental chair, the device dynamically adjusts spinal curvature to replicate motion patterns associated with deep abdominal breathing, similar to Kundalini or Qi Gong breathwork. The device operates automatically, with optional manual adjustments by the researcher.

Primary outcome measures

• Number and type of intervention-related adverse events as assessed by a yoga-specific adverse events questionnaire [Time frame: Throughout the 4-week intervention period]
• Number of participants completing ≥90% of scheduled intervention sessions [Time frame: 4 weeks (intervention period)]
• Mean percentage of completed intervention sessions per participant [Time frame: 4 weeks (intervention period)]
• Number of participants who withdraw from the study before completing intervention [Time frame: 4 weeks (intervention period)]

Secondary outcome measures (12)

• Change in Heart Rate Variability During Therapy over time [Time frame: During each session across 4 weeks]
• Change in vertical postural alignment as measured by digital posture analysis [Time frame: Baseline and 4 timepoints altogether corresponding to 4 treatment weeks]
• Change in spine flexibility as measured by the Thomayer test (in cm) [Time frame: Baseline and weekly]
• Change in nightly average heart rate variability (SMSSD) during sleep as measured by wearable sensors in Milliseconds (ms) [Time frame: Nightly, throughout the 4-week study period]
• Change in nightly average resting heart rate during sleep as measured by wearable sensors (in bpm) [Time frame: Nightly, throughout the 4-week study period]
• Change in nightly average respiratory rate (Breaths per minute) during sleep as measured by wearable sensors [Time frame: Nightly, throughout the 4-week study period]
• Change in cortical hemodynamic activity (HbO and HbR concentrations) at rest and during intervention, measured by fNIRS [Time frame: Baseline, Week 4, and during each intervention session]
• Change in cortical water signal (tissue hydrodynamics) measured by H2O-specific wavelength sensor [Time frame: Baseline, Week 4, and during each intervention session]
• Change in oxidation state of cytochrome c oxidase measured by broadband fNIRS [Time frame: Baseline, Week 4, and during each intervention session]
• Change in nightly sleep stage distribution as measured by PPG-based wearable sensors - Percentage of total sleep time in each of the sleep stages [Time frame: Nightly, over the 4-week intervention period]
• Change in sleep quality subscale score (B-PSQI) from the GlymphActive Questionnaire [Time frame: Baseline and Week 4]
• Change in spatial navigation performance (corrent responses) as measured by the Intersections Spatial Memory Cognitive Task [Time frame: Familiarization at screening, Baseline and Week 4]

Eligibility criteria

Inclusion criteria

• 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)

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Czechia · 2 centers

• Neuro Health Centrum S.R.O — Brno
• Neuropsychiatrie s.r.o., Terronska 580/19 — Prague

Slovakia · 1 center

• AuraMedica s.r.o., Neurologická ambulancia, OMNIA BUSINESS CENTER, Tomášikova 19081/28C — Bratislava

Identifiers

NCT: NCT06989242 · RG-CZSK-PH2 · RG-CZSK-PH2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗