<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04502628</url>
  </required_header>
  <id_info>
    <org_study_id>HBOT for HC</org_study_id>
    <nct_id>NCT04502628</nct_id>
  </id_info>
  <brief_title>Hyperbaric Oxygen Therapy for Hemorrhagic Cystitis Post HSCT</brief_title>
  <official_title>Hyperbaric Oxygen Therapy for the Treatment of Hemorrhagic Cystitis Post Allogeneic Hematopoietic Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shandong Provincial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shandong Provincial Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative&#xD;
      therapy for many malignant or nonmalignant hematological diseases. Hemorrhagic cystitis (HC)&#xD;
      is one of the common and major causes of morbidity in patients undergoing allo-HSCT. Its&#xD;
      incidence ranges from 7 to 52%, and its manifestations range from painless microscopic&#xD;
      hematuria to severe bladder hemorrhage, leading to clot formation within the urinary tract&#xD;
      and even renal failure. This complication results in much pain to the patient and increasing&#xD;
      treatment cost.&#xD;
&#xD;
      Late-onset HC (two weeks after stem cell infusion) has been associated with reactivation of&#xD;
      viruses, including cytomegalovirus, polyoma BK and JC viruses, and adenovirus types I and II.&#xD;
      Former studies have confirmed that the bladder is also considered to be one of the immune&#xD;
      attacked organs in acute graft-versus-host disease (aGVHD). The classic treatments for HC&#xD;
      include hydration, alkalization, and bladder irrigation, immunosuppressant reduction, and&#xD;
      platelet transfusion. Patients with viral infection may be treated with antiviral agents, but&#xD;
      their efficacy is limited. When the HC was considered to be associated with aGVHD, some&#xD;
      immunosuppressive agents such as glucocorticoids will be added in. However, too intensive&#xD;
      immunosuppressive measures leave the patients susceptible to infection and, in turn,&#xD;
      increases the accidence of non-relapse mortality (NRM). The mechanism underlying the&#xD;
      development of HC remains largely unidentified, and its optimal treatment has not yet been&#xD;
      established. It is important to explore novel, less-toxic, higher effective, and&#xD;
      cost-effective strategies to improve HC.&#xD;
&#xD;
      The elevated levels of available oxygen and partial pressure of arterial oxygen provide the&#xD;
      main benefits of Hyperbaric oxygen therapy (HBOT) in clinical practice that addresses these&#xD;
      areas of inadequate or poor tissue healing. HBOT is utilized as primary or adjunctive therapy&#xD;
      for many medical conditions in which tissue damage is triggered by hypoxic injury. The&#xD;
      pharmacological and physiologic effects of HBOT have direct and indirect mechanisms and&#xD;
      effects on reactive oxygen species (ROS) most beneficial to that of wound healing and&#xD;
      antibacterial treatments. HBOT can stimulate fibroblast proliferation, angiogenesis, and&#xD;
      wound healing. It has been shown effective in the treatment of radiation-induced HC by&#xD;
      promoting fibroblast proliferation and capillary angiogenesis, decreasing edema, and&#xD;
      facilitating damaged hypoxic urothelium. Based on the above clinical and pre-clinical&#xD;
      practice, the investigators deduce that HBOT may benefit patients with HC after HSCT. In the&#xD;
      investigators' limited early-onset investigation, the investigators found HBO was largely&#xD;
      successful in 20 patients suffering HC post-allo-HSCT, showed a quick resolution or&#xD;
      improvement of HC. The investigators also observed more rapid responses in patients who&#xD;
      started HBOT earlier after the diagnosis of HC. The investigators confirmed that HBOT was&#xD;
      effective and well-tolerated in the patients, regardless of the infective- or non-infective-&#xD;
      caused HC. Therefore, the investigators design this prospective, randomized, and single-arm&#xD;
      clinical trial to establish the definitive efficacy and safety of HBOT in patients with HC&#xD;
      after allo-HSCT.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Anticipated">September 1, 2021</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response rate of HBOT</measure>
    <time_frame>Six months post-allo-HSCT</time_frame>
    <description>Response rate of HBOT was determined on the basis of HC symptom disppearance and the normal urine routine test result</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and severity of treatment-related adverse events</measure>
    <time_frame>3 years</time_frame>
    <description>Number of participants with treatment-related adverse events and the the severity of these events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Exploratory biomarker analysis</measure>
    <time_frame>3 years</time_frame>
    <description>Exploratory biomarker to predict treatment response</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Stem Cell Transplant Complications</condition>
  <arm_group>
    <arm_group_label>HBOT group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with hemorrhagic cystitis (HC) after allo-HSCT will receive hyperbaric oxygen therapy (HBOT) on the next day of the HC diagnosis was determined. Then HBOT will be scheduled every day until symptoms of HC vanished.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Hyperbaric oxygen therapy</intervention_name>
    <description>Patients with hemorrhagic cystitis (HC) after allo-HSCT will receive hyperbaric oxygen therapy (HBOT) on the next day of the HC diagnosis was determined. Then HBOT will be scheduled every day until symptoms of HC vanished. Other classic measures to treatment HC such as hydration, alkalization, and bladder irrigation will also be carried out at the same time.</description>
    <arm_group_label>HBOT group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients undergoing allogeneic stem cell transplantation&#xD;
&#xD;
          -  Patients develop late-onset hemorrhagic cystitis (HC)&#xD;
&#xD;
          -  The count of neutrophilia cells over 0.5 * 10^9/L, hemoglobin over 60 g/L, platelet&#xD;
             over 30 *10^9/L&#xD;
&#xD;
          -  SGOT/SGPT no more than 2 times of UNL&#xD;
&#xD;
          -  Serum creatinine no more than 1.5 times of UNL&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Early-onset HC post-allo-HSCT&#xD;
&#xD;
          -  Unsuitable to the study due to severe complication such as uncontrolled severe&#xD;
             infection&#xD;
&#xD;
          -  Claustrophobia&#xD;
&#xD;
          -  Ear diseases such as otitis media&#xD;
&#xD;
          -  Eye diseases such as glaucoma&#xD;
&#xD;
          -  Epilepsy history&#xD;
&#xD;
          -  Important organ dysfunction&#xD;
&#xD;
          -  Coagulopathy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xin Wang</last_name>
    <role>Study Chair</role>
    <affiliation>Shandong Provincial Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yujie M JIANG</last_name>
    <phone>8613370506886</phone>
    <phone_ext>8613370506886</phone_ext>
    <email>yujiejiang05@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shandong Provincial Hospital</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <zip>250021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yujie JIANG</last_name>
      <phone>8613370506886</phone>
      <email>yujiejiang05@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>July 30, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>September 6, 2021</last_update_submitted>
  <last_update_submitted_qc>September 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shandong Provincial Hospital</investigator_affiliation>
    <investigator_full_name>Wang Xin</investigator_full_name>
    <investigator_title>Director of Department of Hematology</investigator_title>
  </responsible_party>
  <keyword>allogeneic stem cell transplantation</keyword>
  <keyword>Hemorrhagic cystitis</keyword>
  <keyword>Hyperbaric oxygen treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystitis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04502628
org study id: HBOT for HC
nct id: NCT04502628
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative
      therapy for many malignant or nonmalignant hematological diseases. Hemorrhagic cystitis (HC)
      is one of the common and major causes of morbidity in patients undergoing allo-HSCT. Its
      incidence ranges from 7 to 52%, and its manifestations range from painless microscopic
      hematuria to severe bladder hemorrhage, leading to clot formation within the urinary tract
      and even renal failure. This complication results in much pain to the patient and increasing
      treatment cost.

      Late-onset HC (two weeks after stem cell infusion) has been associated with reactivation of
      viruses, including cytomegalovirus, polyoma BK and JC viruses, and adenovirus types I and II.
      Former studies have confirmed that the bladder is also considered to be one of the immune
      attacked organs in acute graft-versus-host disease (aGVHD). The classic treatments for HC
      include hydration, alkalization, and bladder irrigation, immunosuppressant reduction, and
      platelet transfusion. Patients with viral infection may be treated with antiviral agents, but
      their efficacy is limited. When the HC was considered to be associated with aGVHD, some
      immunosuppressive agents such as glucocorticoids will be added in. However, too intensive
      immunosuppressive measures leave the patients susceptible to infection and, in turn,
      increases the accidence of non-relapse mortality (NRM). The mechanism underlying the
      development of HC remains largely unidentified, and its optimal treatment has not yet been
      established. It is important to explore novel, less-toxic, higher effective, and
      cost-effective strategies to improve HC.

      The elevated levels of available oxygen and partial pressure of arterial oxygen provide the
      main benefits of Hyperbaric oxygen therapy (HBOT) in clinical practice that addresses these
      areas of inadequate or poor tissue healing. HBOT is utilized as primary or adjunctive therapy
      for many medical conditions in which tissue damage is triggered by hypoxic injury. The
      pharmacological and physiologic effects of HBOT have direct and indirect mechanisms and
      effects on reactive oxygen species (ROS) most beneficial to that of wound healing and
      antibacterial treatments. HBOT can stimulate fibroblast proliferation, angiogenesis, and
      wound healing. It has been shown effective in the treatment of radiation-induced HC by
      promoting fibroblast proliferation and capillary angiogenesis, decreasing edema, and
      facilitating damaged hypoxic urothelium. Based on the above clinical and pre-clinical
      practice, the investigators deduce that HBOT may benefit patients with HC after HSCT. In the
      investigators' limited early-onset investigation, the investigators found HBO was largely
      successful in 20 patients suffering HC post-allo-HSCT, showed a quick resolution or
      improvement of HC. The investigators also observed more rapid responses in patients who
      started HBOT earlier after the diagnosis of HC. The investigators confirmed that HBOT was
      effective and well-tolerated in the patients, regardless of the infective- or non-infective-
      caused HC. Therefore, the investigators design this prospective, randomized, and single-arm
      clinical trial to establish the definitive efficacy and safety of HBOT in patients with HC
      after allo-HSCT.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response rate of HBOT
time frame: Six months post-allo-HSCT
description: Response rate of HBOT was determined on the basis of HC symptom disppearance and the normal urine routine test result
measure: Incidence and severity of treatment-related adverse events
time frame: 3 years
description: Number of participants with treatment-related adverse events and the the severity of these events.
measure: Exploratory biomarker analysis
time frame: 3 years
description: Exploratory biomarker to predict treatment response
arm group label: HBOT group
arm group type: Experimental
description: Patients with hemorrhagic cystitis (HC) after allo-HSCT will receive hyperbaric oxygen therapy (HBOT) on the next day of the HC diagnosis was determined. Then HBOT will be scheduled every day until symptoms of HC vanished.
intervention type: Procedure
intervention name: Hyperbaric oxygen therapy
description: Patients with hemorrhagic cystitis (HC) after allo-HSCT will receive hyperbaric oxygen therapy (HBOT) on the next day of the HC diagnosis was determined. Then HBOT will be scheduled every day until symptoms of HC vanished. Other classic measures to treatment HC such as hydration, alkalization, and bladder irrigation will also be carried out at the same time.
arm group label: HBOT group
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Xin Wang
role: Study Chair
affiliation: Shandong Provincial Hospital
last name: Yujie M JIANG
phone: 8613370506886
phone ext: 8613370506886
email: yujiejiang05@126.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shandong Provincial Hospital
investigator full name: Wang Xin
investigator title: Director of Department of Hematology
mesh term: Cystitis
sharing ipd: No