Adjuvant Therapy for Severe COPD Patients in the Stable Phase by an Oxyhydrogen Generator With Nebulizer

Adjuvant Therapy for Severe COPD Patients in the Stable Phase by an Oxyhydrogen Generator With Nebulizer: A Multi-centric, Randomized, Parallel-control and Double-blinded Clinic Study

The purpose for this study is to determine safety and effectiveness of the oxyhydrogen generator with nebulizer through an adjuvant therapy for the severe COPD patients in the stable phase.

Study Overview

• Status: Unknown
• Conditions: COPD
• Intervention / Treatment: Device: oxyhydrogen; Drug: Conventional treatment; Device: Oxygen

Detailed Description

In this study, severe COPD patients in stable phase who were included in both treatment and control groups, administered randomly oxyhydrogen generator with nebulizer (treatment group) or oxygen Nebulizer Machine （control group ）for adjuvant therapy. The therapeutic outcomes in both treatment and control groups are analyzed and evaluated to verify safety and effectiveness of the test product.This study is a multi-center, randomized, double-blind study. The trial lasted for 3 months. The curative effect was observed for subjects in the second week, first month, second month and third month respectively as the observing time point. Total patients which are planned to be included are 140 cases, where, 70 cases in the treatment group and control group respectively are distributed in 5 clinical hospitals.

• Study Type: Interventional
• Enrollment (Anticipated): 170
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • First Affiliated Hospital of Guangzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. It conforms to the diagnostic criteria of chronic obstructive pulmonary diseases (COPD): (PFT)The percentage of forced expiratory volume in forced vital capacity in one second after inhaling vasodilator (FEV1 / FVC% < 70%);
2. Classification of COPD severity by pulmonary function: The criterion for this study is Severe: FEV1/FVC<0.70, and FEV1< 50% expected value after pulmonary function was examined by taking bronchodilator.
3. More than 40 years old and have normal ability to judge independently; men and women are not limited;
4. Living in the vicinity of the test centre in the past six months; -

Exclusion Criteria:

• 1) Those who have acute exacerbation in the past 4 weeks; 2) Lung disease history: Excluding the history of other lung diseases except combined COPD, such as combined pulmonary tuberculosis and diffuse pan-capillary bronchiolitis, pneumonia, pneumothorax, pleural effusion, pulmonary embolism, etc.

  3) Those who suffer infectious diseases such as hepatitis A, hepatitis B, AIDS and tuberculosis or connective tissue diseases in the active period; 4) Those who suffer high fever, as well as various local or systemic infections (including respiratory, urinary and reproductive system, digestive system, sepsis, etc.), severe infection, especially lung infection found by CT examination; 5) Those who have limited ability to understand and poor compliance; do not have the legal capacity or limited legal capacity; participated in other clinical trials in the first 3 months when they were included in the groups; mental or physical disability; 6) Those who were difficult to make an exact evaluation on safety and effectiveness of products; 7) The women in pregnancy and lactation, as well as the women at childbearing age who don't agree to take effective contraceptive measures during the study period; 8) Those who have abnormal heart function and thrombophlebitis; 9) Those who are known and can't stand the oxygen and hydrogen inhalation; 10) Those who are suffered from primary diseases in important visceral organs and systems, such as stroke, severe hypertension, gastric ulcer, uncontrolled diabetes, malignant tumor, liver and kidney failure, and severe heart disease history (acute myocardial infarction, congestive heart failure and other heart diseases in the acute phase); 11) Cancer in progressive stage as well as undetermined masses found in the treatment; 12) Those who have one or more lobectomy history; 13) Those who are suspected to have or really have alcohol and drug abuse history; 14) Those whose AST and ALT≥120U/L, Ccr≤50ml/min; who have shock or unstable hemodynamics; 15) Those who are considered not to participate in clinical trials by the investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: oxyhydrogen; conventional treatment (bronchodilator (LABA,LAMA) with or without ICS)+ hydrogen/ oxygen inhaled	Device: oxyhydrogen; Hydrogen/oxygen mixed gas inhaled(proportion 2:1),3 L/min . 1 hour each time,twice a day(BID).Test Duration is three months.; Other Names: Oxyhydrogen generator with nebulizer; Drug: Conventional treatment; Bronchodilator (LABA,LAMA) with or without ICS.Conventional treatment is invariable with which was given to COPD patients in 3 months before the study.; Other Names: medication treatment
EXPERIMENTAL: oxygen; conventional treatment (bronchodilator (LABA,LAMA) with or without ICS)+ oxygen inhaled	Drug: Conventional treatment; Bronchodilator (LABA,LAMA) with or without ICS.Conventional treatment is invariable with which was given to COPD patients in 3 months before the study.; Other Names: medication treatment; Device: Oxygen; oxygen inhaled,3 L/min . 1 hour each time,twice a day(BID).Test Duration is three months.; Other Names: Medical molecular sieve oxygenerator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in dyspnea index score (mMRC score) at 3 months	baseline and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in St George's respiratory questionnaire (SGRQ score) at 3 months		baseline and 3 months
Change from Baseline in Six minute walk distance at 3 months		baseline and 3 months
Change from Baseline in Pulmonary artery pressure measured by heart color Doppler ultrasound at 3 months		baseline and 3 months
Change from Baseline in Forcibly vital capacity(FVC) at 3 months		baseline and 3 months
Change from Baseline in First second forcibly expiration quantity(FEV1) at 3 months		baseline and 3 months
Change from Baseline in mean maximum expiratory flow(MMEF) at 3 months		baseline and 3 months
Change from Baseline in Residual volume(RV) at 3 months		baseline and 3 months
Change from Baseline in Serum interleukin-6(IL-6) at 3 months		baseline and 3 months
Change from Baseline in Serum interleukin-8( IL - 8) at 3 months		baseline and 3 months
Change from Baseline in Serum tumor necrosis factor-a(TNF-a) at 3 months		baseline and 3 months
Change from Baseline in Serum malondialdehyde (MDA) at 3 months		baseline and 3 months
Change from Baseline in Serum 8-isoprostane at 3 months		baseline and 3 months
Change from Baseline in Arterial oxygen tension (PaO2) at 3 months		baseline and 3 months
Change from Baseline in carbon dioxide arterial tension (PaCO2) at 3 months		baseline and 3 months
number of participants with adverse events	the adverse events including chest distress,wheezing,cough,heartbeat accelerating,abdominal pain,diarrhea,nausea,vomiting,cardiac,liver, renal toxicity , etc.	up to 3 months

Collaborators and Investigators

• Sponsor: Shanghai Asclepius Meditec Inc.
• Collaborators: The Second Hospital of Hebei Medical University; West China Hospital; The First Affiliated Hospital of Guangzhou Medical University; Tianjin Medical University General Hospital; Second Affiliated Hospital of Guangzhou Medical University
• Investigators: Study Chair: Zhong N Shan, academician, First Affiliated Hospital of Guangzhou Medical University

Publications and helpful links

General Publications

• 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.
• Liu FT, Xu SM, Xiang ZH, Li XN, Li J, Yuan HB, Sun XJ. Molecular hydrogen suppresses reactive astrogliosis related to oxidative injury during spinal cord injury in rats. CNS Neurosci Ther. 2014 Aug;20(8):778-86. doi: 10.1111/cns.12258. Epub 2014 Mar 31.
• Kohama K, Yamashita H, Aoyama-Ishikawa M, Takahashi T, Billiar TR, Nishimura T, Kotani J, Nakao A. Hydrogen inhalation protects against acute lung injury induced by hemorrhagic shock and resuscitation. Surgery. 2015 Aug;158(2):399-407. doi: 10.1016/j.surg.2015.03.038. Epub 2015 May 14.
• Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study. J Clin Biochem Nutr. 2010 Mar;46(2):140-9. doi: 10.3164/jcbn.09-100. Epub 2010 Feb 24.
• Xiao M, Zhu T, Wang T, Wen FQ. Hydrogen-rich saline reduces airway remodeling via inactivation of NF-kappaB in a murine model of asthma. Eur Rev Med Pharmacol Sci. 2013 Apr;17(8):1033-43.
• Ning Y, Shang Y, Huang H, Zhang J, Dong Y, Xu W, Li Q. Attenuation of cigarette smoke-induced airway mucus production by hydrogen-rich saline in rats. PLoS One. 2013 Dec 20;8(12):e83429. doi: 10.1371/journal.pone.0083429. eCollection 2013.
• Zheng J, Liu K, Kang Z, Cai J, Liu W, Xu W, Li R, Tao H, Zhang JH, Sun X. Saturated hydrogen saline protects the lung against oxygen toxicity. Undersea Hyperb Med. 2010 May-Jun;37(3):185-92.
• Kawamura T, Wakabayashi N, Shigemura N, Huang CS, Masutani K, Tanaka Y, Noda K, Peng X, Takahashi T, Billiar TR, Okumura M, Toyoda Y, Kensler TW, Nakao A. Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo. Am J Physiol Lung Cell Mol Physiol. 2013 May 15;304(10):L646-56. doi: 10.1152/ajplung.00164.2012. Epub 2013 Mar 8.
• Huang CS, Kawamura T, Peng X, Tochigi N, Shigemura N, Billiar TR, Nakao A, Toyoda Y. Hydrogen inhalation reduced epithelial apoptosis in ventilator-induced lung injury via a mechanism involving nuclear factor-kappa B activation. Biochem Biophys Res Commun. 2011 May 6;408(2):253-8. doi: 10.1016/j.bbrc.2011.04.008. Epub 2011 Apr 5.
• Sun Q, Cai J, Liu S, Liu Y, Xu W, Tao H, Sun X. Hydrogen-rich saline provides protection against hyperoxic lung injury. J Surg Res. 2011 Jan;165(1):e43-9. doi: 10.1016/j.jss.2010.09.024. Epub 2010 Oct 15.

Study record dates

Study Major Dates

• Study Start: July 15, 2016
• Primary Completion (ANTICIPATED): July 21, 2020
• Study Completion (ANTICIPATED): December 20, 2020

Study Registration Dates

• First Submitted: July 22, 2016
• First Submitted That Met QC Criteria: July 28, 2016
• First Posted (ESTIMATE): July 29, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 2, 2020
• Last Update Submitted That Met QC Criteria: April 1, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: COPD; hydrogen
• Other Study ID Numbers: ZZheng

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: the main evaluation index and the secondary evaluation index of all participants will be share in 3 months after the end of this study.