A First-in-Human, Dose-Escalation Study to Evaluate the Safety and Tolerability of Intravenous Hydrogen-Oxygen Ultrafine Bubbles in Adults
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The goal of this clinical trial is to learn whether hydrogen-oxygen ultrafine bubbles can be safely given through a vein (intravenous infusion) to adults. This is a first-in-human study, meaning this type of infusion has not been tested in people before. The study focuses on safety and does not aim to treat or prevent any disease.
The main questions this study aims to answer are: 1) Can hydrogen-oxygen ultrafine bubbles be given safely without causing serious or unacceptable side effects? 2) What dose range can be given safely to adults for future research?
About 40 adult participants, including healthy volunteers or people with mild, stable health conditions, will take part in the study. Each participant will receive two intravenous infusions, given one week apart. Some participants will receive a higher dose during the second infusion, depending on their assigned study group.
Researchers will closely monitor participants before, during, and after each infusion. This includes checking vital signs, heart activity, and blood tests. The study will also collect exploratory laboratory measurements, such as markers related to oxygen levels and oxidative stress, to help guide the design of future studies.
Participants will be followed for safety for about three weeks after starting the study. The information gained from this research will help determine whether hydrogen-oxygen ultrafine bubbles can be studied further in clinical research.
详细描述
Hydrogen-oxygen ultrafine bubbles (UFB-HHO) are a novel gas-liquid formulation designed to deliver molecular hydrogen and oxygen in the form of nanoscale bubbles suspended in an aqueous solution. While molecular hydrogen administered by inhalation has been investigated in prior clinical and preclinical studies, the intravenous administration of hydrogen-oxygen ultrafine bubbles has not previously been evaluated in humans. Preclinical investigations conducted by the study investigators in animal models have demonstrated the feasibility of intravenous UFB-HHO administration and have not identified acute safety concerns at the dose ranges planned for initial human evaluation, supporting progression to a first-in-human clinical study.
This study is designed as a first-in-human, single-blind, dose-escalation clinical trial to characterize the safety, tolerability, and acceptable dose range of intravenously administered UFB-HHO in adults. The study follows a predefined, safety-review-guided cohort progression strategy, with dose advancement contingent on review of accumulated safety data by a study safety review committee. The primary intent of this study is safety evaluation; it is not designed to assess clinical efficacy.
Participants will receive two intravenous administrations of UFB-HHO, administered one week apart, according to the assigned dose cohort. A sentinel cohort is included to provide early safety confirmation at the lowest planned dose prior to enrollment of subsequent dose-escalation cohorts. Following the sentinel phase, sequential cohorts will evaluate higher second-dose levels while maintaining a consistent initial dose, allowing assessment of tolerability with within-participant dose escalation. This approach is intended to minimize risk while enabling efficient characterization of dose-related safety findings.
Intravenous infusions will be administered using standard clinical infusion equipment at a controlled infusion rate. Participants will undergo structured safety monitoring before, during, and after each infusion. Safety evaluations include clinical observation, vital sign measurements, electrocardiographic monitoring, and laboratory testing. Particular attention is given to infusion-related reactions, cardiopulmonary parameters, and laboratory indicators relevant to hematologic, hepatic, renal, coagulation, inflammatory, hemolytic, and complement activation pathways.
In addition to safety monitoring, the study incorporates exploratory physiological and biochemical assessments intended to characterize biological responses associated with UFB-HHO administration. These exploratory evaluations include measurements related to tissue oxygenation, oxidative stress, and metabolic indicators. Data from these assessments are intended to support dose selection and inform the design of subsequent clinical studies; they are not intended to establish clinical efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
This study is single-blind. Participants are blinded to the specific dose level of the investigational product they receive. Investigators and clinical staff are not blinded, as knowledge of the administered dose is required for safety monitoring, dose escalation decisions, and clinical management. No other parties are masked.
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults aged 30 to 60 years at the time of enrollment.
- •Judged to be healthy or to have mild, stable, well-controlled medical conditions based on medical history, physical examination, vital signs, and screening laboratory assessments.
- •Body mass index (BMI) within 18.5 to 30.0 kg/m².
- •Able and willing to comply with all study procedures and scheduled visits.
- •Able to understand the study procedures and provide written informed consent prior to participation.
排除标准
- •History or presence of clinically significant cardiovascular, pulmonary, neurological, hepatic, renal, hematologic, or immunologic disease that, in the investigator's judgment, could increase risk or interfere with study participation.
- •Known history of stroke, transient ischemic attack, myocardial infarction, heart failure, or significant arrhythmia.
- •Active infection, inflammatory condition, or febrile illness within 14 days prior to screening.
- •Abnormal baseline laboratory findings considered clinically significant by the investigator.
- •Known hypersensitivity or allergy to components of the investigational infusion or intravenous administration materials.
- •Current or recent (within 30 days) participation in another interventional clinical study.
- •Use of investigational drugs or therapies within 30 days prior to enrollment.
- •Pregnancy or breastfeeding. Women of childbearing potential who are unwilling to use effective contraception during the study period.
- •Any condition that, in the investigator's opinion, would make participation unsafe or compromise interpretation of study results.
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: From first infusion (Day 0) through approximately 21 days after first infusion.
Number and proportion of participants who experience one or more treatment-emergent adverse events following intravenous administration of hydrogen-oxygen ultrafine bubbles. Adverse events will be assessed for severity, seriousness, and relationship to the investigational intervention.
Number of Participants With Clinically Significant Laboratory Abnormalities
时间窗: From baseline through approximately 21 days after first infusion.
Number of participants with laboratory test results that meet predefined criteria for clinically significant abnormalities following administration of hydrogen-oxygen ultrafine bubbles. Laboratory assessments include hematology, renal function, hepatic function, coagulation parameters, markers of hemolysis, inflammatory markers, and complement activation markers.
次要结局
- Change From Baseline in Oxidative Stress Biomarker: Malondialdehyde (MDA)(From baseline through approximately 21 days after first infusion.)
- Change From Baseline in Antioxidant Enzyme Activity: Superoxide Dismutase (SOD)(From baseline through approximately 21 days after first infusion.)
- Change From Baseline in Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)-Related Biomarker Levels(From baseline through approximately 21 days after first infusion.)
研究者
Olly Indrajani Dewi
Principal Investigator
Yayasan Inovasi Molekuler Indonesia (Indonesia Molecular Innovation Foundation)