Safety Assessment of Molecular Hydrogen Inhalation in Patients With Mild Cognitive Impairment

An open-label, one-arm, single-center clinical study tested safety and efficacy of one hour daily dosage of H2 gas in a form of inhalation. Dosage is administered during morning hours every working day according to detailed instructions to study participants.

Primary objective: To verify the safety of hydrogen gas inhalation on a sample of patients with mild cognitive impairment (according to the objective opinion of the physician) and diagnosed mild to moderate form of dementia, as well as to verify cognitive abilities via tests from prof. MUDr. Aleš Bartoš, Ph.D. - ALBA (Amnesia Light and Brief Assessment) and POBAV (Naming of pictures and their equipment).

Secondary objective: To assess the effect on specific health indicators (e.g. inflammation, antioxidant capacity, metabolism) by blood sampling as well as blood pressure/pulse measurement and BMI.

Primary endpoint: Inhalation Safety, Questionnaire - Subjective Assessment (ALBA and POBAV).

Secondary endpoints: Biochemical indicators (e.g. inflammation, antioxidant status), blood analysis and BP/Pulse + BMI.

Study population: 50-80 years old participants with mild cognitive declin in overall good health condition.

Inclusion criteria:

• patients diagnosed with mild cognitive impairment (MCI) with an overall good health condition
• generally good health, with the ability to perform daily
• activities independently (modified Rankin score 0-2, Barthel index minimum 70 points)
• age between 50 and 80 years, ensuring inclusion of individuals within the typical risk range for cognitive decline
• a reliable study partner or caregiver who can provide accurate information about the participant's cognitive and functional abilities throughout the study
• stable medical condition, without major fluctuations in health status that could interfere with cognitive assessments
• signed informed consent, ensuring that participants understand the study protocol and potential risks

Exclusion criteria:

• pregnancy or lactation, as the safety of hydrogen inhalation therapy in these populations has not been established
• use of medications or investigational treatments that could significantly affect cognitive function or interfere with study outcomes
• history of severe psychiatric disorders such as major depression, bipolar disorder, or schizophrenia, which may independently influence cognitive performance
• history of cerebrovascular events, including recent stroke or transient ischemic attack, which may confound cognitive outcomes
• severe cardiovascular diseases, including uncontrolled hypertension, recent myocardial infarction, or heart failure, that could pose additional risks during the study
• chronic kidney disease (stage 3 or higher), as impaired renal function may alter systemic metabolism and affect the study's findings
• significant respiratory disorders, such as severe chronic obstructive pulmonary disease (COPD) or restrictive lung diseases, that could impact the safety of hydrogen inhalation
• known hypersensitivity or allergic reactions to materials used in the hydrogen delivery system, such as nasal cannulas or facial masks
• recent participation in another clinical trial within the past 90 days, to prevent potential interactions and ensure unbiased study results Duration of the study for each participant: 24 weeks (12 weeks of hydrogen inhalation + 12 weeks withou hydrogen inhalation) This pilot study is not designed for formal hypothesis testing; its purpose is to gather descriptive safety data and estimate effect sizes for future research. We will enroll 30 participants to gather enough information on safety, tolerability, and feasibility.

The primary analysis will concentrate on the frequency and severity of adverse events (AEs/SAEs) and ALBA + POBAV scores to evaluate cognitive changes. Descriptive statistics will summarize adverse events, vital signs, and lab results.

In the secondary analysis, we will assess variations in biochemical markers (inflammation, antioxidant capacity, metabolism) and physiological metrics (blood pressure, pulse, BMI) using paired t-tests or Wilcoxon signed-rank tests, depending on how the data is distributed.

Any missing safety data will be conservatively imputed, and multiple imputation techniques will be utilized for efficacy measurements. While there is no formal interim analysis planned, continuous safety monitoring will be carried out.

Results will be shared through summary statistics, tables, and appropriate graphical representations, offering preliminary insights into the feasibility and potential advantages of molecular hydrogen inhalation therapy.