IHT for Mild Cognitive Impairment

Overseen By Elaina Smith

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of North Texas Health Science Center

Disqualifiers: AD-dementia, Uncontrolled conditions, Depression, others

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach called intermittent hypoxia training (IHT) to determine its safety and effectiveness for people with mild cognitive impairment (MCI). Participants will breathe either low-oxygen air or normal air through a mask for short periods, three times a week, for up to 12 weeks. It suits adults aged 55 to 79 with MCI who can visit the lab regularly. The trial aims to improve memory and thinking skills using a non-drug method. As an unphased trial, it provides a unique opportunity to explore innovative, non-drug treatments for cognitive health.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it requires that any chronic conditions you have are controlled and stabilized for at least 6 months.

What prior data suggests that intermittent hypoxia training is safe for treating mild cognitive impairment?

Research shows that intermittent hypoxia training (IHT) is generally safe for patients. Studies found that older adults with mild cognitive impairment (MCI) managed the treatment well. Participants in these studies breathed air with less oxygen for short periods, followed by normal air, several times a week. The aim was to see if this could improve memory and thinking skills.

No major side effects were reported from IHT in these studies, indicating that participants did not experience serious health problems. While some might have felt mild discomfort, the overall findings suggest that IHT is safe for humans, especially those with MCI. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about IHT (Intermittent Hypoxic Training) for mild cognitive impairment because it introduces a unique mechanism by using controlled exposures to low-oxygen air (10% O2). Unlike standard treatments like cognitive therapy and medications that focus on symptom management, IHT aims to stimulate brain adaptation and resilience through hypoxic conditioning. This innovative approach could enhance cognitive function by promoting neuroplasticity and improving brain oxygen utilization, potentially offering a non-invasive and drug-free alternative for cognitive enhancement.

What evidence suggests that intermittent hypoxia training is effective for mild cognitive impairment?

This trial will compare the effects of Intermittent Hypoxia Training (IHT) with a Sham-IHT control for mild cognitive impairment (MCI). Research has shown that IHT might help improve MCI. One study explored whether IHT could aid learning and memory by lowering harmful proteins in the brain. Early results suggested that IHT is safe and may enhance brain function in older adults with memory issues. While it has benefited other health conditions, its specific impact on MCI remains under investigation. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 55-79 with mild cognitive impairment (MCI). Participants must be depression-free, post-menopausal if female, have certain stable chronic conditions, and able to visit the lab. Exclusions include major upcoming surgery, current severe illnesses like uncontrolled hypertension or diabetes, recent high-altitude living, metal implants, or claustrophobia to facemasks.

Inclusion Criteria

I can breathe through a special mask with less oxygen.

You should not have depression when you join the study.

My chronic conditions like high blood pressure or diabetes have been stable for at least 6 months.

Exclusion Criteria

You are currently in another research study or have been in a study that involved low oxygen levels, like living at high altitudes or being in a hypoxia training program.

I have had a severe head or brain injury, or a stroke.

I currently have COVID-19.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo intermittent hypoxia training (IHT) or sham-IHT control for up to 12 weeks, with 3 sessions per week

12 weeks

3 sessions per week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IHT Treatment
• Sham-IHT Control

Trial Overview The study tests intermittent hypoxia training (IHT) versus a sham control over 12 weeks to see if it's safe and effective for improving memory in people with MCI. Participants will breathe moderately hypoxic air through a mask and are randomly assigned to either the treatment or placebo group.

How Is the Trial Designed?

Group I: IHT Treatment Experimental Treatment 1 Intervention

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.

Group II: Sham-IHT control Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

University of North Texas Health Science Center

Lead Sponsor

Trials

41

Recruited

20,800+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Intermittent hypoxia-hyperoxia training (IHHT) showed potential benefits in improving cognitive function and altering inflammatory markers in both healthy elderly individuals and patients with mild cognitive impairment (MCI), based on a study involving 29 participants over 15 sessions.

The study found that IHHT led to significant changes in pro-inflammatory factors, such as increased levels of GDF15 and MMP9 activity, which may contribute to adaptive cellular responses that could help combat cognitive decline associated with Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment. Serebrovska, ZO., Xi, L., Tumanovska, LV., et al.[2023]

Cognitive training (CT) significantly improved cognitive abilities and quality of life in 39 individuals with mild cognitive impairment related to Parkinson's disease, as evidenced by better scores on cognitive assessments like the Addenbrooke's Cognitive Examination III and the Trail Making Test.

Participants in the experimental group showed notable improvements in various cognitive measures and self-reported quality of life, suggesting that engaging in cognitive activities can be beneficial for patients with Parkinson's disease and mild cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of cognitive intervention on cognitive symptoms and quality of life in idiopathic Parkinson's disease: a randomized and controlled study. Sousa, NMF., Neri, ACDM., Brandi, IV., et al.[2022]

In a 24-week trial involving subjects with mild cognitive impairment (MCI), donepezil did not show significant benefits on primary cognitive measures, indicating limited efficacy for this treatment in MCI.

However, some positive effects were observed in secondary outcomes and in a fully evaluable group, suggesting that longer trials and more sensitive measures could improve the assessment of donepezil's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Key lessons learned from short-term treatment trials of cholinesterase inhibitors for amnestic MCI. Salloway, S., Correia, S., Richardson, S.[2022]

Cognitive Training (CT) in patients with Mild Cognitive Impairment (MCI) and early Alzheimer's Disease (AD) showed variable effects on brain structure and function, with some studies indicating increased cortical thickness and grey matter volumes, but no changes in hippocampal volumes.

The review included 19 studies, highlighting significant heterogeneity and variable quality, suggesting that while CT may lead to changes in brain activation and connectivity, more robust research is needed to clearly link these changes to clinical improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimaging Outcomes in Studies of Cognitive Training in Mild Cognitive Impairment and Early Alzheimer's Disease: A Systematic Review. Beishon, L., Intharakham, K., Swienton, D., et al.[2021]

A pilot study involving 8 healthy adults exposed to 9 hours of intermittent nocturnal hypoxia for 28 nights showed no significant changes in sleep quality, alertness, or cognitive functions like attention and working memory.

While overall sleep quality worsened, the study identified specific respiratory disturbances, such as hyperoxic central apneas, but these did not translate into cognitive deficits, suggesting that short-term intermittent hypoxia may not impair cognitive performance in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of sleep, cognition, and respiration under 4 weeks of intermittent nocturnal hypoxia in adult humans. Weiss, MD., Tamisier, R., Boucher, J., et al.[2021]

Cognitive training (CT) was found to be feasible and acceptable for both healthy older adults and individuals with mild cognitive impairment (MCI) or dementia, with 37 participants providing positive feedback after 12 weeks of training.

Participants reported several benefits from CT, including enjoyment and improved cognitive awareness, but also faced barriers such as technology issues and emotional challenges, particularly those with dementia, highlighting the need for tailored approaches in future implementations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Qualitative Analysis of the Cognition and Flow (CoGFlowS) Study: An Individualized Approach to Cognitive Training for Dementia Is Needed. Beishon, L., Haunton, V., Subramaniam, H., et al.[2021]

SaiLuoTong (SLT) significantly improved cognitive functions, particularly in delayed memory retrieval and executive function, in a study of 78 participants with mild cognitive impairment (MCI) over 12 weeks.

The treatment was well tolerated by participants aged 60 and older, suggesting it could be a safe option for enhancing cognitive abilities in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled, parallel-group 12-week pilot phase II trial of SaiLuoTong (SLT) for cognitive function in older adults with mild cognitive impairment. Steiner-Lim, GZ., Bensoussan, A., Andrews-Marney, ER., et al.[2023]

Chronic intermittent hypoxia (CIH) significantly increased levels of amyloid-β42 in the brains of triple transgenic Alzheimer's disease mice, suggesting that obstructive sleep apnea (OSA) could worsen Alzheimer's pathology.

In vitro studies showed that intermittent hypoxia also raised amyloid-β42 levels in human neuroblastoma cells, indicating a direct effect of hypoxia on Alzheimer's-related protein accumulation, which could inform early detection and intervention strategies for OSA in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic intermittent hypoxia/reoxygenation facilitate amyloid-β generation in mice. Shiota, S., Takekawa, H., Matsumoto, SE., et al.[2022]

Intermittent hypoxia (AH) significantly prevented memory impairment in rats with experimental Alzheimer's disease, suggesting it may protect cognitive function.

AH also reduced oxidative stress and completely prevented nitric oxide overproduction in the brain, indicating its potential as a protective mechanism against neurodegeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prevention of the brain neurodegeneration in rats with experimental Alzheimer's disease by adaptation to hypoxia]. Manukhina, EB., Goriacheva, AV., Barskov, IV., et al.[2016]

Intermittent hypoxia training (IHT) was found to be safe and effective in improving short-term memory and attention in elderly patients with amnestic mild cognitive impairment (aMCI), as evidenced by significant improvements in mini-mental state examination and digit span scores after 8 weeks of training.

IHT also led to beneficial physiological changes, including a reduction in resting arterial pressures and an increase in cerebral tissue oxygenation, suggesting that this training may enhance brain function by improving oxygen delivery to the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Hypoxia Training for Treating Mild Cognitive Impairment: A Pilot Study. Wang, H., Shi, X., Schenck, H., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10624018/

Intermittent Hypoxia Training for Treating Mild Cognitive ... Although intermittent hypoxia training (IHT) has proven effective against various clinical disorders, its impact on mild cognitive impairment (MCI) is unknown.

2. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.674688/full

Intermittent Hypoxia Training Prevents Deficient Learning- ... This study tested the hypothesis that IHT improves learning-memory behavior, diminishes Aβ accumulation in cerebral cortex and hippocampus, and enhances ...

3. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/1533317519896725

Intermittent Hypoxia Training for Treating Mild Cognitive ... This pilot study examined IHT's safety and therapeutic efficacy in elderly patients with amnestic MCI (aMCI).

4. sciencedirect.com sciencedirect.com/science/article/pii/S2352873717300021

Intermittent hypoxic–hyperoxic training on cognitive ... A very recent study reported that IHHT improved exercise performance in athletes with overtraining syndrome [25]. The case study of Susta et al. reported a ...

5. unthsc-ir.tdl.org unthsc-ir.tdl.org/items/618bf39d-7c5a-4e99-b9af-9203d175d4f4

novel intervention for treating mild cognitive impairment This study was to test if IHT was safe as a novel intervention for treating patients with MCI. Methods: MCI patients (age 69±3) alternately breathed 10% O2 and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31902230/

Intermittent Hypoxia Training for Treating Mild Cognitive ... This pilot study examined IHT's safety and therapeutic efficacy in elderly patients with amnestic MCI (aMCI).

7. researchgate.net researchgate.net/publication/338404478_Intermittent_Hypoxia_Training_for_Treating_Mild_Cognitive_Impairment_A_Pilot_Study

Intermittent Hypoxia Training for Treating Mild Cognitive ... This pilot study examined IHT's safety and therapeutic efficacy in elderly patients with amnestic MCI (aMCI).