Clinical Trial of Hydrogen-Rich Celsior Solution Applied in Aging DBD Liver/Kidney Transplantation (HRCSDBD)

Hydrogen-Rich Celsior Solution Improve the Quality of Aging DBD Grafts in Liver/Kidney Transplantation: Prospective, Randomized Clinical Trial

The purpose of this study is to investigate whether hydrogen-rich Celsior solution improve the quality of aging grafts in liver/kidney transplantation.

Study Overview

• Status: Unknown
• Conditions: Evidence of Liver Transplantation
• Intervention / Treatment: Drug: Hydrogen-Rich Celsior Solution

Detailed Description

The organ shortage has been rising to impede the development of organ transplantation.To find a solution, transplantation center is working on the application of marginal grafted liver or renal, especially the aging grafts. The most common inducement of organ dysfunction during the perioperation is liver/renal ischemia-reperfusion (I/R) injury, caused by the generation of cytotoxic oxygen radicals. Hydrogen gas is a kind of reducing gas, which has been reported to display antioxidant properties and protective effects against organ dysfunction induced by various I/R injuries. Investigators will investigate whether hydrogen-rich Celsior solution improve the quality of aging grafts in liver/ kidney transplantation.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200127
    • Deparment of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Ren Ji Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Donors:

1. Age of the donor ≥60 yrs.
2. The donor has no historical records of drug abuse, alcoholic abuse, homosexual,or drug addiction, etc.
3. Evaluate infections and infectious disease of the donor.
4. History of malignant tumor;
5. History of hypertension, diabetes, hemophilia, or other anticoagulant disease,kidney donor should not have a history of kidney disease.
6. Daily urine volume is approximately normal.
7. Donor should be subjected to physical examination by medical doctor of OPO stuff before donation; the OPO stuff should realize whether the potential donor has infected lesion or not, such as abscess, ulcer, lymphadenectasis， etc., and evaluate infectious risk of recipient post-operationally.
8. OPO stuff should realize the dynamic change of body temperature, as well as various intensive care parameters of the potential donor, it shall be very important to be sure whether the potential donor has pulmonary/ systemic infections or not,especially for whom has longer ICU duration (> 7 Days).
9. The potential donor should has a systolic blood pressure ≥ 50 mm Hg (1mmHg=0.133 kPa) and arterial SaO > 80%.
10. Liver Biochemistry: alanine aminotransferase (ALT) ≤ 6ULN, total bilirubin (TBil) ≤ 50umol/L;Kidney Biochemistry: serum creatinine (sCre) ≤ 2ULN;
11. Negative anti-HIV antibody;
12. Negative bacterial and fungal culture in blood;
13. Ultrasonic diagnosis of fatty liver, trauma, hematoma, lithiasis, etc., as well as size of both kidney, hydronephrosis, nephrolithiasis, etc. if possible.
14. Graft liver should be soft, normal color and even, no tumor or other abnormity;steatosis ≤ 30% by liver biopsy.Graft kidneys should have complete renal capsule with no congestion or bleeding;proximal tubular necrosis ≤ 50%, without obvious structural damage.Organ (liver and kidney) cold ischemia time (CIT) is determined as the time duration from cold preservation of organs to transplant re-perfusion. CIT of aging DBD liver and kidney graft should be ≤ 10 and16 hours, respectively.

Recipients：

1. Aged between 18-65 years old
2. MELD score ≤25,BMI≤25
3. Patients with tumor,the expected lifetime≥6 months
4. Agree to anticipate the trial and sign the informed consent

Exclusion Criteria:

• Donor's age < 60 yrs;
• The donor has historical records of drug abuse, alcoholic abuse, homosexual, or drug addiction, etc.
• The donor is HIV infected, or has severe infection, or positive bacterial and/ or fungal culture results;
• Uncontrollable hypertension, diabetics;
• Malignant tumor;
• Unstable hemodynamic response or SaO status, such as systolic pressure <50 mm Hg (1mmHg=0.133 kPa) , or arterial SaO<80%.
• Liver Biochemistry: alanine aminotransferase (ALT)>6ULN, total bilirubin (TBil)>50umol/L;
• Graft liver has a steatosis >30%, or graft kidney has a proximal tubular necrosis>50% or obvious glomerular sclerosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydrogen-rich Celsior solution; Using aging liver grafts（≥60 years old)，lavaged and cold stored with hydrogen-rich Celsior solution for 2-4 hours.	Drug: Hydrogen-Rich Celsior Solution; Before the procedure, add hydrogen gas into Celsior solution. After harvesting the liver/kidney grafts, lavage and cold store the grafts with Hydrogen-Rich Celsior Solution.; Other Names: HR solution
No Intervention: Celsior solution; Using aging liver/kidney grafts（≥60 years old）, lavaged and cold stored with common Celsior solution for 2-4 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Aspartate Aminotransferase(AST)/Alanine Aminotransferase(ALT)	up to 6 months
Change From Baseline in direct bilirubin(DBil)/total bilirubin(TBil)	up to 6 months
Change From Baseline in creatinine	up to 6 months
Change From Baseline in glomerular filtration rate（GFR）	up to 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Pathological score of liver/kidney preservation injury during surgery	during surgery
Mitochondrial function index of hepatocyte/nephrocyte during surgery	during surgery
The total incidence of adverse events/incidence of severe adverse events	up to 6 months
postoperative complications	up to 6 months
Early graft function incidence	baseline and 6 months
Graft dysfunction incidence	baseline and 6 months
Recipient survival	baseline and 6 months

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Study Director: Xia Qiang, investigator, Deparment of Liver Surgery

Publications and helpful links

General Publications

• Abe T, Li XK, Yazawa K, Hatayama N, Xie L, Sato B, Kakuta Y, Tsutahara K, Okumi M, Tsuda H, Kaimori JY, Isaka Y, Natori M, Takahara S, Nonomura N. Hydrogen-rich University of Wisconsin solution attenuates renal cold ischemia-reperfusion injury. Transplantation. 2012 Jul 15;94(1):14-21. doi: 10.1097/TP.0b013e318255f8be.
• Qian L, Shen J. Hydrogen therapy may be an effective and specific novel treatment for acute graft-versus-host disease (GVHD). J Cell Mol Med. 2013 Aug;17(8):1059-63. doi: 10.1111/jcmm.12081. Epub 2013 Jun 7.
• Buchholz BM, Masutani K, Kawamura T, Peng X, Toyoda Y, Billiar TR, Bauer AJ, Nakao A. Hydrogen-enriched preservation protects the isogeneic intestinal graft and amends recipient gastric function during transplantation. Transplantation. 2011 Nov 15;92(9):985-92. doi: 10.1097/TP.0b013e318230159d.
• Liu Y, Yang L, Tao K, Vizcaychipi MP, Lloyd DM, Sun X, Irwin MG, Ma D, Yu W. Protective effects of hydrogen enriched saline on liver ischemia reperfusion injury by reducing oxidative stress and HMGB1 release. BMC Gastroenterol. 2014 Jan 12;14:12. doi: 10.1186/1471-230X-14-12.
• Noda K, Shigemura N, Tanaka Y, Bhama J, D'Cunha J, Kobayashi H, Luketich JD, Bermudez CA. Hydrogen preconditioning during ex vivo lung perfusion improves the quality of lung grafts in rats. Transplantation. 2014 Sep 15;98(5):499-506. doi: 10.1097/TP.0000000000000254.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): February 1, 2017
• Study Completion (Anticipated): February 1, 2017

Study Registration Dates

• First Submitted: October 24, 2015
• First Submitted That Met QC Criteria: November 20, 2015
• First Posted (Estimate): November 24, 2015

Study Record Updates

• Last Update Posted (Estimate): November 24, 2015
• Last Update Submitted That Met QC Criteria: November 20, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Kidney Transplantation; oxidative stress; organ preservation; Hydrogen; Ischemia-Reperfusion Injury
• Additional Relevant MeSH Terms: Pharmaceutical Solutions
• Other Study ID Numbers: RenJiH-20151020