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

66 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

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 data supports the effectiveness of the treatment IHT for Mild Cognitive Impairment?

Research shows that intermittent hypoxia training (IHT) can improve short-term memory and attention in elderly patients with mild cognitive impairment by enhancing brain oxygenation and blood flow. Another study found that a similar approach, intermittent hypoxia-hyperoxia training, improved cognitive function and reduced inflammation in patients with mild cognitive impairment. ^{1 2 3 4 5}

How is IHT Treatment different from other treatments for mild cognitive impairment?

IHT Treatment (Intermittent Hypoxia Training) is unique because it involves exposing patients to short periods of low oxygen levels, which is different from other treatments like cognitive training or cholinesterase inhibitors that focus on enhancing brain function through exercises or chemicals. This approach is novel as it uses a physiological method to potentially improve cognitive function. ^{6 7 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Intermittent Hypoxia Training for Treating Mild Cognitive Impairment: A Pilot Study. [2020]

2. Switzerland 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. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Chronic intermittent hypoxia/reoxygenation facilitate amyloid-β generation in mice. [2022]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Prevention of the brain neurodegeneration in rats with experimental Alzheimer's disease by adaptation to hypoxia]. [2016]

5. Netherlands pubmed.ncbi.nlm.nih.gov

A pilot study of sleep, cognition, and respiration under 4 weeks of intermittent nocturnal hypoxia in adult humans. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Qualitative Analysis of the Cognition and Flow (CoGFlowS) Study: An Individualized Approach to Cognitive Training for Dementia Is Needed. [2021]

7. United States 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. [2023]

8. Brazil 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Key lessons learned from short-term treatment trials of cholinesterase inhibitors for amnestic MCI. [2022]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Neuroimaging Outcomes in Studies of Cognitive Training in Mild Cognitive Impairment and Early Alzheimer's Disease: A Systematic Review. [2021]