Safety and Efficacy of Intermittent hypoxiс-hyperoxiс Personalized Training Sessions for the Creation of an Organoprotective Phenotype in Elderly People SHIELD
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Incidence of intolerance to IHHT sessions (a combined endpoint including individual intolerance showing discomfort that does not allow the Subject to continue the IHHT sessions and/or the incidence of one of the complications of IHHT sessions (disorde
研究概览
简要总结
This study investigates an original protocol of personalized hypoxic-hyperoxic preconditioning utilizing a personalized approach on the basis of cerebral tissue oxygenation assessed with near-infrared spectroscopy. 20 healthy elderly volunteers will be randomized into two equal groups. Subjects of the experimental group will undergo personalized sessions of intermittent hypoxic-hyperoxic training (IHHT) based on the cerebral tissue oximetry index assessed with near-infrared spectroscopy with a target reduction of 20%. Subjects of the control group (sham treatment) will undergo placebo procedures with atmospheric air.
详细描述
- Rationale for the study conduction Chronic diseases, surgical interventions, aging and the effects of drugs and environmental factors have an adverse health effect on the human body. Therefore, the development of novel techniques and improvement of existing methods for organ protection and health preservation is one of the most crucial tasks of modern medicine.
The term preconditioning refers to describing the phenomenon of increasing the tolerance of a cell, tissue, organ or organism as a whole to the effects of a damaging factor (e.g., ischemia, hypoxia, surgical trauma) as a result of preliminary exposure to sub-damaging stress stimuli. There are various approaches to the implementation of this phenomenon including ischemic preconditioning, pharmacological preconditioning, hypoxic preconditioning and remote preconditioning.
Of great interest is the concept of hypoxic preconditioning in which the body is deprived of adequate oxygen supply at the tissue level, which contributes to the implementation of a protective phenotype in all organs and tissues. In practice, this technique is usually implemented as an intermittent delivery of hypoxic and normoxic gas mixtures, but recently its modification in which the normoxic phase is replaced by a hyperoxic one has become popular. The method demonstrates promising results, but is not applicable in practice, since most of the completed studies analyze IHHT sessions as a long-term therapy, which is not feasible in a hospital setting.
The major task is selecting the optimal mode demonstrating both efficacy and feasibility as well as personalizing the IHHT, which justifies the need for this study. 2. Known and potential risks for the study Subjects This is a prospective, single-blind, randomized, placebo-controlled study. This study will include subjects without serious chronic diseases or with diseases during the compensatory stage; therefore the therapy does not carry potential risks. This is confirmed by Uzun et al., 2023, whose systematic review assessed the outcomes of 16 studies of IHHT and intermittent hypoxic-normoxic training conducted on patients with various diseases.
Since the sessions will be personalized according to cerebral tissue oximetry utilizing near-infrared spectroscopy with a target reduction of 20% in the hypoxic phase of the session, such adverse reactions as impaired consciousness up to the onset of a syncope are possible, as this variable has not been previously assessed in IHHT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 60-74 years.
- •Signed informed consent.
- •Non-inclusion criteria
- •Charlson Comorbidity Index ≤ 3 (with a score of 1 or more on all criteria except for the age factor).
- •Conditions associated with chronic hypoxia or hyperoxia.
- •Uncompensated coronary artery disease.
- •Chronic diseases in the acute or decompensated phase.
排除标准
- •Withdrawal from further participation in the study (revocation of informed consent), unrelated to any of the subsequent points.
- •Inability to reduce cerebral tissue saturation by 20% from baseline during the hypoxic test.
- •Individual intolerance to IHHT sessions.
- •Development of one of the following complications during IHHT sessions:
- •. Disorder of consciousness. 2). The state of syncope. 3). Development of any other life-threatening condition.
- •The fact and the reason for the Subject to be excluded from the study will be recorded in the CRF (Case Report Form), along with all data collected during the study, for further analysis, if planned.
- •If exclusion occurs according to points 1 and 2 of the exclusion criteria, the subject will be replaced with another participant. If exclusion occurs according to any of the subsequent points, replacement will not be performed.
- •If exclusion occurs according to points 3 and 4, patients will be thoroughly examined and remain under the observation of the study physicians until their condition is stabilized
研究组 & 干预措施
Control group
ambient air (FiO2 = 21%) will be delivered for 3 days 1 time a day for 45 minutes
干预措施: Sham treatment (Drug)
Main group
FiO2 reduced by 20% will be delivered for 6 minutes alternating with 34% FiO2 for 3 minutes (45 minutes in total as 5 full circles) within 3 days 1 time a day
干预措施: FiO2 reduced by 20% alternating with 34% FiO2 (Drug)
结局指标
主要结局
Incidence of intolerance to IHHT sessions (a combined endpoint including individual intolerance showing discomfort that does not allow the Subject to continue the IHHT sessions and/or the incidence of one of the complications of IHHT sessions (disorde
时间窗: Periprocedural
The difference in the incidence of intolerance to IHHT sessions (percent)
次要结局
- Serum NF-κB - nuclear factor-kappa B (ng/mL)(Baseline, Day 3, Day 4)
- Serum Nrf2 - Nuclear erythroid-related factor 2 (ng/mL)(Baseline, Day 3, Day 4)
- Fraction of inspired oxygen (FiO2) required for reducing cerebral tissue oxygenation based on near-infrared spectroscopy by 20% from the baseline (percent)(Periprocedural)
- Serum HIF-1α - hypoxia-inducible factor 1-alpha (pg/mL)(Baseline, Day 3, Day 4)
- Respiratory rate (RR) (brpm)(6, 9, 15, 18, 24, 27, 33, 36, and 45 minutes from the initiation of the IHHT session)
- Systolic blood pressure levels (SBP) (mmHg)(6, 9, 15, 18, 24, 27, 33, 36, and 45 minutes from the initiation of the IHHT session)
- Diastolic blood pressure levels (DBP) (mmHg).(6, 9, 15, 18, 24, 27, 33, 36, and 45 minutes from the initiation of the IHHT session)
- Heart rate (HR) (bpm)(6, 9, 15, 18, 24, 27, 33, 36, and 45 minutes from the initiation of the IHHT session)
- Saturation of peripheral oxygen (SpO2) levels (percentage)(6, 9, 15, 18, 24, 27, 33, 36, and 45 minutes from the initiation of the IHHT session)
- End tidal carbon dioxide (etCO2) levels (mmHg)(6, 9, 15, 18, 24, 27, 33, 36, and 45 minutes from the initiation of the IHHT session)
- Incidence of intolerance to IHHT sessions (percent)(Periprocedural)
- Incidence of one of the complications of IHHT sessions (percent)(Periprocedural)
- HIF-1α - hypoxia-inducible factor 1-alpha in venous blood mononuclear cell nuclei (pg/mL)(Baseline, Day 4)
- NF-κB - nuclear factor-kappa B in venous blood mononuclear cell nuclei (ng/mL)(Baseline, Day 4)
- Nrf2 - Nuclear erythroid-related factor 2 in venous blood mononuclear cell nuclei (ng/mL)(Baseline, Day 4)
- BIS ( Bispectral Index) monitoring (Units)(6, 9, 15, 18, 24, 27, 33, 36, and 45 minutes from the initiation of the IHHT session)
- PSV - Maximum peak systolic velocity measured by transcranial Doppler Ultrasound (cm/s)(Baseline, Day 4)
- Maximum peak T velocity measured by transcranial Doppler ultrasound (cm/s)(Baseline, Day 4)
- TAMAX - time-averaged maximum velocity measured by transcranial Doppler ultrasound (cm/s)(Baseline, Day 4)
- TAMEAN - time-averaged mean velocity measured by transcranial Doppler ultrasound (cm/s)(Baseline, Day 4)
- VF - volume flow measured by transcranial Doppler ultrasound (mL/s)(Baseline, Day 4)
- RI - resistivity index measured by transcranial Doppler ultrasound (units)(Baseline, Day 4)
- Peak velocity in the basal vein of Rosenthal on transcranial Doppler ultrasound (cm/s)(Baseline, Day 4)
- PSV - peak systolic velocity in the middle cerebral artery (MCA) measured by transcranial Doppler ultrasound (cm/s)(Baseline, Day 4)
研究者
Nikolay Kamenshchikov
Principal Investigator
Tomsk National Research Medical Center of the Russian Academy of Sciences