HBOT in the Treatment and Prevention of aGVHD

Hyperbaric Oxygen Therapy Improve Acute Graft-Versus-Host Disease in Patients Underwent Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic strategy for patients with hematopoietic malignancies. However, the therapeutic benefits and wider application of allo-HSCT are limited by acute graft-versus-host disease (aGVHD), the latter remains a major obstacle against long-term survival for this population. New aGVHD prophylactic and therapeutic strategies that are superior in efficacy, safety, cost-effectiveness, and less technically demanding are still in desperate need. Hyperbaric oxygen therapy (HBOT) has been confirmed as an effective and economical therapeutic modality for hemorrhagic cystitis (HC) whether induced by infection or acute graft-versus-host disease (aGVHD) for transplant recipients. However, little is known about its involvement in aGVHD. In this study, the investigators designed a randomized, controlled, and open clinical trial to confirm the safety and efficacy of HBOT on aGVHD in patient underwent allo-HSCT.

Study Overview

• Status: Recruiting
• Conditions: Hyperbaric Oxygen Therapy; Acute-graft-versus-host Disease
• Intervention / Treatment: Device: Hyperbaric oxygen therapy

Detailed Description

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic strategy for patients with hematopoietic malignancies. However, the therapeutic benefits and wider application of allo-HSCT are limited by acute graft-versus-host disease (aGVHD), the latter remains a major obstacle against long-term survival for this population. New aGVHD prophylactic and therapeutic strategies that are superior in efficacy, safety, cost-effectiveness, and less technically demanding are still in desperate need.

Although a variety of immune and non-immune cells are involved in the development of aGVHD, reactive oxygen species (ROS) has been proved as the primary triggers of the inflammatory response and play a key role in the pathogenesis of aGVHD. Therefore, strategies targeting ROS production are crucial for effectively managing aGVHD. Hyperbaric oxygen therapy (HBOT) is a well-established treatment method, which is used to improve non-healing ulcers secondary to aGVHD and hemorrhagic cystitis (HC) after allo-HSCT whether induced by infection or aGVHD. Even the exact mechanism is not fully understood, HBOT was demonstrated to reduce a series of pro-inflammatory cytokines release and can improve the action of antibiotics.

In this study, the investigators plan to initiate a randomized, controlled, and open clinical cohort study confirm the safety and efficacy of HBOT on aGVHD in patient underwent allo-HSCT.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yujie Jiang, Dr.; Phone Number: 86-13370506886; Email: yujiejiang05@126.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250021
      • Recruiting
      • Shandong Provincial Hospital
      • Contact: Xiaoming Zhou, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients undergoing allogeneic stem cell transplantation
• Patients develop aGVHD
• The count of neutrophilia cells over 0.5 * 109/L, hemoglobin over 60 g/L, platelet over 30 *109/L
• Signed informed consent

Exclusion Criteria:

• Unsuitable to the study due to severe complication such as uncontrolled severe infection
• Claustrophobia
• Ear diseases such as otitis media
• Eye diseases such as glaucoma
• Epilepsy history
• Important organ dysfunction
• Coagulopathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: aGVHD-HBOT; Patients after allo-HSCT will receive hyperbaric oxygen therapy (HBOT) on the next day of the aGVHD diagnosis was determined.	Device: Hyperbaric oxygen therapy; Patients with aGVHD treated with HBOT every two days
No Intervention: aGVHD-HBOT free; Patients after allo-HSCT will NOT receive hyperbaric oxygen therapy (HBOT) on the next day of the aGVHD diagnosis was determined.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate of HBOT as complete response or partial response for the treatment of aGVHD	Complete or partial response rate of HBOT for the treatment of aGVHD will be measured using Bayesian method.	Four years
Incidence of aGVHD when HBOT was administrated as prophylaxis measurement at one month after transplant	At one month after transplant, HBOT will be administrated every three days (up to 6 times) to recipients without aGVHD evidence, the incidence of aGVHD will be counted.	100 days post transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival rate	Will be summarized by frequency and 95% confidence interval. The distribution of time-to-event endpoints will be estimated by Kaplan-Meier estimate. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazards regression will be employed for multivariate analysis on time-to-event outcomes.	Four years
Leukemia-free survival rate	Will be summarized by frequency and 95% confidence interval. The distribution of time-to-event endpoints will be estimated by Kaplan-Meier estimate. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazards regression will be employed for multivariate analysis on time-to-event outcomes.	Four years
Relapse rate	Relapse rate of recipients will be measured using Bayesian method. Will be summarized by frequency and 95% confidence interval.	Four years
Incidence of adverse events of HBOT	Toxicities will be summarized by grade and by their relationship to treatment.	Four years

Collaborators and Investigators

• Sponsor: Shandong Provincial Hospital
• Investigators: Study Chair: Xiaoming Zhou, Dr., Shandong Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): October 10, 2021
• Primary Completion (Anticipated): August 10, 2024
• Study Completion (Anticipated): August 10, 2025

Study Registration Dates

• First Submitted: September 6, 2021
• First Submitted That Met QC Criteria: October 13, 2021
• First Posted (Actual): October 14, 2021

Study Record Updates

• Last Update Posted (Actual): October 14, 2021
• Last Update Submitted That Met QC Criteria: October 13, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: HBOT in aGVHD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No