Memory Impairment, Mild Cognitive Impairment
Conditions
Keywords
intermittent hypoxia training or preconditioning
Brief summary
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).
Detailed description
Volunteer subjects 55-79 years age will sign an informed consent and complete a medical history form. The number of recruited minority subjects will be targeted to approximate the ethnic/racial demographics of the general population in Fort Worth-Dallas area. After they pass the physical screening, all subjects must have an orientation visit in the lab to ensure the ability to tolerate wearing a face masker and breathing hypoxia air up to 5 minutes. In addition, they must undergo a series of cognitive assessments including clinical dementia rating to be determined to have MCI. Only the subjects who have been diagnosed with MCI are eligible to enroll to the study. Up to 66 MCI subjects will be recruited and assigned to two groups: intervention group to have intermittent hypoxia training (IHT) or control group with sham-IHT. The subjects in IHT group will breathe 10% O2 up to 5-min periods alternated with 5-min recovery on room air, repeated for 8 cycles per session, 3 sessions/week up to 12 weeks. The subjects in sham-IHT group will breathe 21% O2 and room air, each 5 min per cycle, for 8 cycles per session, 3 sessions/week for 12 weeks. Before and after 12-week interventions, the subjects' cognitive performances (including short-term memory, concentration ability, visuospatial orientation, and executive function), cardiovascular function during mental, physical and physiological challenges, blood plasma EPO, BDNF, and beta-amyloid proteins, carotid arterial morphology and function, brain MRI will be assessed and compared. In addition, the subjects' short-term memory, concentration ability, visuospatial orientation, and executive function in both groups will be assessed after 5-week and 8-week interventions to determine the IHT effect of a dose-response on the cognitive functions.
Interventions
DEVICEIHT Treatment
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.
OTHERSham-IHT Control
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.
Sponsors
University of North Texas Health Science Center
University of Texas Southwestern Medical Center
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
IHT vs Sham-IHT Control
Eligibility
Sex/Gender
ALL
Age
55 Years to 79 Years
Healthy volunteers
No
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), 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Cognitive Function | Change from baseline after 12-week interventions | Change in scores or points (from 0 to 30) in Mini-mental State Examination. Higher scores indicate better testing performance or function. |
| Attention and Short-term Memory | Change from baseline after 12-week interventions with IHT or sham-IHT | Change in scores or points in California-Verbal Learning Test - 2nd edition (CVLT-II), and Brief Visuospatial Memory Test - Revised (BVMT-R). Immediate Free-Recall (FR) and delay FR for word-verbal memory and visuospatial memory. |
| Cognitive Function in digit-verbal memory | Change from baseline after 12-week interventions | Change in scores or points in Digit-Span test - Forward, backward and sequence. Digit-Span recalls test attention and short-term memory. More correct recalls indicate better testing performance and function in digit-verbal memory. |
| Visual Orientation and Executive Function | Change from baseline after 12-week interventions | Change in time to complete Trail-making tests. Less time (in sec) to complete the tests indicates better performance and function in executive function, attention and processing speed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brain Morphology | before vs after up to 12-week intervention | Cortical volume assessed by brain MRI scans. Increased cerebral cortical gray matter indicates a better outcome. |
Countries
United States
Contacts
CONTACTXiangrong Shi, PhD
Outcome results
None listed