Safety Study of Intravenous Hydrogen-Oxygen Ultrafine Bubbles in Adults

NCT07357909 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: IMIF-202512-SiGNA-HHO-FIH
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteer

Keywords

Hydrogen oxygen nanobubbles; Intravenous infusion; First-in-human study; Dose escalation; Safety; Tolerability; Healthy volunteers; Oxidative stress biomarkers; Tissue oxygenation; Redox biology

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  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.

  From first infusion (Day 0) through approximately 21 days after first infusion.

• Number of Participants With Clinically Significant Laboratory Abnormalities

  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.

  From baseline through approximately 21 days after first infusion.

Secondary Outcomes (3)

• 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.

Study Arms (1)

Experimental: Intravenous Hydrogen-Oxygen Ultrafine Bubbles

EXPERIMENTAL

Participants in this single-arm study receive intravenous hydrogen-oxygen ultrafine bubbles. The intervention is administered in two infusions given one week apart. Dose escalation is implemented across sequential cohorts based on review of accumulated safety data.

Other: Hydrogen-Oxygen Ultrafine Bubbles

Interventions

Hydrogen-Oxygen Ultrafine Bubbles OTHER

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.

Experimental: Intravenous Hydrogen-Oxygen Ultrafine Bubbles

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yayasan Inovasi Molekuler Indonesia (Indonesia Molecular Innovation Foundation): lead
• PT Raho Noble Corp: collaborator

Study Sites (1)

Ben Mari Hospital

Malang, East Java, 60217, Indonesia

Location

Related Publications (13)

• 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.

  BACKGROUND

• Aulanni'am, A., Riawan, W., Dyah Kinasih, W., Sri Widyarti, S., & Olly Indrayani, P. (2025). Uji Toksisitas Gelembung Nano Gasotransmitter. Institut Molekul Indonesia.

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• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

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• Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol. 2007;47:89-116. doi: 10.1146/annurev.pharmtox.46.120604.141046.

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  PMID: 21601655 BACKGROUND

Central Study Contacts

Aditya T Hernowo, M.D., Ph.D.

CONTACT

+62 823-2601-7575; hernowo@molecularinnovation.id

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a sequential, dose-escalation study in which participants are enrolled in predefined cohorts. An initial sentinel cohort receives the lowest planned dose to confirm safety. Subsequent cohorts are enrolled sequentially and receive higher dose levels based on review of accumulated safety data from preceding cohorts. Dose escalation and cohort progression are guided by predefined safety review criteria. All participants receive the investigational intervention according to their assigned cohort, with structured safety monitoring following each administration.

Study Record Dates

• First Submitted: December 30, 2025
• First Posted: January 22, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)