IHT for Mild Cognitive Impairment

Study Overview
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Brief Summary
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This phase I clinical trial will examine the safety and efficacy of intermittent hypoxia training (IHT) for up to 12 weeks to treat subjects with mild cognitive impairment (MCI).

Official Title
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Intermittent Hypoxia Training: A Novel Therapy for Mild Cognitive Impairment

Conditions
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Mild Cognitive Impairment, Memory Impairment

Intervention / Treatment
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* Device: IHT Treatment
* Other: Sham-IHT Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult men and women ages 55 to 79 years old who have been diagnosed with MCI. Must be willing to be assigned to either group: treatment or sham-treatment control. Able to pay multiple visits to the lab for the proposed assessments. Able to breathe moderately hypoxic air via an air-cushioned, disposable facemask. To have controlled stabilized chronic conditions of at least 6 months duration, such as hypertension, coronary artery disease, diabetes or metabolic disease, chronic bronchitis, degenerative osteoporosis or arthritis and/or other aging-related chronic conditions. Must be depression-free at the time of enrollment. Must have arterial oxygen saturation at or above 95% and cerebral tissue oxygenation at or above 50% at rest. Woman subject must be post-menopausal. Exclusion Criteria: Unwilling to sign a written consent to participate in this double-blinded placebo-controlled phase I trial. Diagnosed with AD-dementia or have impaired independent daily functioning; with MMSE <20 and/or CDR ≥1. Unable to visit the lab independently. Claustrophobic to facemask and hyper-reactive to hypoxia exposure. Expecting any major surgery or transplant. Have un-controlled chronic conditions including systolic-diastolic pressures over 150/90 mmHg with medications, diabetes, chronic renal failure (based on the medical history questionnaire), obstructive sleep apnea (based on the medical history), recurrent chest pain, seizures or epilepsies, moderate to severe carotid stenosis or calcification, brain aneurysm, uncontrolled allergic rhinitis, pulmonary fibrosis, emphysema, cancer, infectious disease, atrial fibrillation, regular pre-mature ventricular contractions, myocardial ischemia or infarct, 2nd or 3rd degree atrio-ventricular blockade. Have severe head injury or traumatic brain injury, stroke (hemorrhagic and/or ischemic). Have currently diagnosed depression. Currently have COVID-19. Have any metallic implants or who are claustrophobic. Currently participating in any interventional study and/or have been previously exposed to hypoxia, such as residing more than two months at altitudes above 5000 ft. within the past 3 years or previously participated in a hypoxia training study.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: IHT vs Sham-IHT Control
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IHT Treatment<br>Exposures to hypoxic air (10% O2) up to 5 min intermittent with up to 5 min recovery (breathing room air) per session, 3 sessions/week, up to 12 weeks. | Device: IHT Treatment<br>* IHT Treatment: IH exposure to 10% O2 for up to 5 min, interspersed with breathing room air recovery for up to 5 min, with up to 8 cycles/session, 3 sessions/week, for up to 12 weeks.<br>|
| Placebo Comparator: Sham-IHT control<br>Exposures to normoxic air (21% O2) up to 5 min intermittent with up to 5 min recovery (breathing room air) per session, 3 sessions/week, up to 12 weeks. | Other: Sham-IHT Control<br>* Sham-IHT Control: Exposure to 21% O2 for up to 5 min, interspersed with breathing room air recovery for up to 5 min, with up to 8 cycles/session, 3 sessions/week, for up to 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Cognitive Function | Change in scores or points (from 0 to 30) in Mini-mental State Examination. Higher scores indicate better testing performance or function. | Change from baseline 5-week, 8-week, and up to 12-week intervention | 
| Attention and Short-term Memory | Change in scores or points in California-Verbal Learning Test - 2nd edition. Immediate Free-Recall (FR), short-delay FR and long-delay FR for words. More FR words indicate better testing performance and function. | Change from baseline 5-week, 8-week, and up to 12-week intervention | 
| Cognitive Function | Change in scores or points in Digit-Span test. Two different sets of Forward (from 3 to 9 digits) and Backward (from 2 to 8 digits) Digit-Span recalls test attention and short-term memory. More correct recalls indicate better testing performance and function. | Change from baseline 5-week, 8-week, and up to 12-week intervention | 
| Visual Orientation and Executive Function | Change in time to complete Trail-making tests. Less time (in sec) to complete the tests indicates better performance and function. | Change from baseline 5-week, 8-week, and after up to 12-week intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurotoxic Protein | Blood beta-amyloid assessed by enzyme-linked immunosorbent assay. Decreased concentrations indicate a better outcome. | before vs after up to 12-week intervention | 
| Neuroprotective Protein | Blood erythropoietin assessed by enzyme-linked immunosorbent assay. Increased concentrations indicate a better outcome. | before vs after up to 12-week intervention | 
| Cerebral Vascular Function | Blood volume flow of carotid artery assessed by ultrasonography. Improved volume flow and vascular compliance in carotid arteries indicate a better outcome. | before vs after up to 12-week intervention | 
| Brain Morphology | Thickness of cortical gray matter assessed by brain MRI. Increased cerebral cortical gray matter indicates a better outcome. | before vs after up to 12-week intervention |