IHT for Mild Cognitive Impairment

Intermittent Hypoxia Training: A Novel Therapy for Mild Cognitive Impairment

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).

Study Overview

• Status: Recruiting
• Conditions: Mild Cognitive Impairment; Memory Impairment
• Intervention / Treatment: Device: IHT Treatment; Other: Sham-IHT Control

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.

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiangrong Shi, PhD; Phone Number: 817-735-2073; Email: xiangrong.shi@unthsc.edu

Study Locations

• United States
  • Texas
    • Fort Worth, Texas, United States, 76107
      • Recruiting
      • University of North Texas Health Science Center
      • Contact: Xiangrong Shi, PhD; Phone Number: 8177352689; Email: xiangrong.shi@unthsc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IHT Treatment; 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; 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.
Placebo Comparator: Sham-IHT control; 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; 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.

What is the study measuring?

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 after 12-week interventions
Attention and Short-term Memory	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.	Change from baseline after 12-week interventions with IHT or sham-IHT
Cognitive Function in digit-verbal memory	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.	Change from baseline after 12-week interventions
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 in executive function, attention and processing speed.	Change from baseline after 12-week interventions

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Morphology	Cortical volume assessed by brain MRI scans. Increased cerebral cortical gray matter indicates a better outcome.	before vs after up to 12-week intervention

Collaborators and Investigators

• Sponsor: University of North Texas Health Science Center
• Collaborators: National Institute on Aging (NIA); University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2023
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: July 13, 2022
• First Submitted That Met QC Criteria: August 8, 2022
• First Posted (Actual): August 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: intermittent hypoxia training or preconditioning
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Neurocognitive Disorders; Cognition Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Cognitive Dysfunction; Memory Disorders
• Other Study ID Numbers: R01AG076675 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The summary results information of the trial will be shared, which will include participants' demographic and baseline characteristics, intermittent hypoxia training outcomes (including biosamples data) and statistical analyses, adverse events, and administrative information. All of the submitted results will be de-identified; no participant ID or identifiable information will be included in the shared results information.
• IPD Sharing Time Frame: 9 months after publication of major data for 3 years
• IPD Sharing Access Criteria: Sharing the data by creating a record of the study in the Global Alzheimer's Association interactive Network (GAAIN.org).
• IPD Sharing Supporting Information Type: SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No