Safety Study of Intravenous Hydrogen-Oxygen Ultrafine Bubbles in Adults

Официальное название

A First-in-Human, Dose-Escalation Study to Evaluate the Safety and Tolerability of Intravenous Hydrogen-Oxygen Ultrafine Bubbles in Adults

Обзор

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.

Подробное описание

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.

Participant follow-up includes scheduled safety assessments after each infusion and continued observation following completion of dosing to identify any delayed or resolving adverse events. The overall study duration per participant is approximately three weeks from first infusion to completion of planned safety follow-up, with additional follow-up conducted as needed for unresolved safety findings.

The results of this study are expected to define a recommended dose range of UFB-HHO suitable for further clinical investigation and to provide foundational human safety data to support future studies of this investigational platform.

Вмешательства

• Другое Hydrogen-Oxygen Ultrafine Bubbles
  Hydrogen-oxygen ultrafine bubbles are administered as an intravenous infusion using standard clinical infusion equipment. Participants receive two infusions given one week apart according to the assigned dose cohort. Dose escalation across cohorts is guided by predefined safety review criteria.

Первичные конечные точки

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: From first infusion (Day 0) through approximately 21 days after first infusion.]
• Number of Participants With Clinically Significant Laboratory Abnormalities [Срок оценки: From baseline through approximately 21 days after first infusion.]

Вторичные конечные точки (3)

• Change From Baseline in Oxidative Stress Biomarker: Malondialdehyde (MDA) [Срок оценки: From baseline through approximately 21 days after first infusion.]
• Change From Baseline in Antioxidant Enzyme Activity: Superoxide Dismutase (SOD) [Срок оценки: From baseline through approximately 21 days after first infusion.]
• Change From Baseline in Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)-Related Biomarker Levels [Срок оценки: From baseline through approximately 21 days after first infusion.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Индонезия · 1 центр

• Ben Mari Hospital — Malang

Публикации

• Hernowo, A. T., Widyarti, S., & Aristyani, S. (2024). Evaluating the safety and therapeutic efficacy of intravenous hydrogen nanobubble infusions in a hypercholesterolemic rat model. Berkala Penelitian Hayati, 30(1), 40-47.
• Aulanni'am, A., Riawan, W., Dyah Kinasih, W., Sri Widyarti, S., & Olly Indrayani, P. (2025). Uji Toksisitas Gelembung Nano Gasotransmitter. Institut Molekul Indonesia.
• Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, Hrobjartsson A, Mann H, Dickersin K, Berlin JA, Dore CJ, Parulekar WR, Summerskill WS, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013 Feb 5;158(3):200-7. doi: 10.7326/0003-4819-158-3-201302050-00583. PMID 23295957
• Agustin V, Hernowo A. Stability evaluation of oxyhydrogen and hydrogen nanobubbles under thermal and pH stress conditions. Sci Rep. 2025 Dec 22;15(1):44273. doi: 10.1038/s41598-025-27868-z. PMID 41430413
• Food and Drug Administration, HHS. International Conference on Harmonisation; Guidance on M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals; availability. Notice. Fed Regist. 2010 Jan 21;75(13):3471-2. PMID 20349552
• Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007 Jun;13(6):688-94. doi: 10.1038/nm1577. Epub 2007 May 7. PMID 17486089
• Ichihara M, Sobue S, Ito M, Ito M, Hirayama M, Ohno K. Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. Med Gas Res. 2015 Oct 19;5:12. doi: 10.1186/s13618-015-0035-1. eCollection 2015. PMID 26483953
• Agarwal A, Ng WJ, Liu Y. Principle and applications of microbubble and nanobubble technology for water treatment. Chemosphere. 2011 Aug;84(9):1175-80. doi: 10.1016/j.chemosphere.2011.05.054. PMID 21689840

Идентификаторы

NCT: NCT07357909 · IMIF-202512-SiGNA-HHO-FIH

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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