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Autologous Bone Marrow Harvest and Transplant for Sensorineural Hearing Loss

Primary Purpose

Sensorineural Hearing Loss

Status
Suspended
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous Bone Marrow Infusion
Sponsored by
James Baumgartner, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sensorineural Hearing Loss

Eligibility Criteria

2 Years - 6 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Evidence of sensorineural hearing loss that is,

    • Bilaterally Moderate or Profound in degree
    • Symmetrical or asymmetrical configuration
    • Sudden or progressive in presentation
  2. Normally shaped cochlea, as determined by Magnetic Resonance Imaging or computed tomography (CT)

  3. The loss must be considered:

    • Acquired
    • Unknown with genetic testing negative. (Genetic testing is not required for Cytomegalovirus (CMV) positive children due to Cytomegalovirus (CMV) known to be number one cause of hearing loss)
  4. Fitted for hearing aids no later than six months post detection of loss unless not recommended by treating audiologist or physicians
  5. Enrollment in a parent/child intervention program
  6. Age 2 years - 6 years old at time of infusion with 2 to 4 years of time elapsed since diagnosis of hearing loss at the time of bone marrow mononuclear fraction (BMMF) infusion.
  7. Ability of the child and caregiver to travel to Orlando, and stay for at least 4 days, and to return for all follow-up visits.

Exclusion Criteria:

  1. Inability to obtain all pertinent medical records:

    • (pertinent physician notes, speech language pathology notes, laboratory findings, test results and imaging studies-must be sent to the research team at least prior to the subject arriving at the study location for preliminary screening and eligibility assessment, preferably14 days before the scheduled visit.)

  2. Known history of:

    • Recently treated (ear or any infections) infection less than 2 weeks before infusion.
    • Renal disease of altered renal function as defined by serum creatinine > 1.5 mg/dl at admission.
    • Hepatic disease or altered liver function as defined by Alanine Transaminase (SGPT) > 150 U/L, and or Total Bilirubin > 1.3 mg/dL
    • Malignancy
    • Immunosuppression as defined by White Blood Cell (WBC) < 3,000 at admission
    • Human Immunodeficiency Virus (HIV)
    • Hepatitis B
    • Hepatitis C
    • Pneumonia, or chronic lung disease requiring oxygen
  3. Any evidence of active maternal infection during the pregnancy
  4. Participation in a concurrent intervention study
  5. Mild hearing loss with no evidence of moderate of severe loss
  6. Unwillingness or inability to stay for 4 days following infusion (should problems arise following the infusion) and to return for the one month, six month and one year follow-up visits.
  7. Evidence of conductive hearing loss
  8. Documented recurrent middle ear infections which are frequent (>5 per year)
  9. Otitis media at the time of examination
  10. Before 2 years from identification of hearing loss at time of infusion
  11. After 4 years from identification of hearing loss at time of infusion

  12. Diagnosis of the following syndromic cause for hearing loss

    • CHARGE
    • Waardenburg
    • Brachio-Oto-Renal
    • Pendred
    • Alport
    • Treacher-Collins
    • Usher
    • Stickler Syndrome

Sites / Locations

  • Florida Hospital for Children

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Autologous bone marrow infusion

Arm Description

One time administration of autologous bone marrow mononuclear cells intravenously, minimum dose of 6 million cells per kg Total nucleated cells.

Outcomes

Primary Outcome Measures

physiological parameter: Blood Pressure
Assessing change from baseline systolic blood pressure to post stem cell infusion systolic blood pressure. The metric for summarizing measurements is millimeters of mercury.
physiological parameter: Pulmonary Endothelial Damage
Measured by the number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Change: Number of Participants With Treatment-Related Adverse Events as Assessed by Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 for Hepatic Injury
The reticuloendothelial system can sequester immature blood elements, theoretically resulting in hepatic injury. An acute elevation of the aspartate transaminase (AST) and Alanine Aminotransferase test (ALT) hepatic enzymes >5.0 - 20.0 x upper limit normal (ULN) in the first 24 hours post infusion will trigger the stopping rules. This level corresponds to the Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 Grade 3 adverse event. It is unlikely that "end vessel" microthrombosis would occur in the liver due to the dual blood supply of the liver and the lung is the first pass organ. This will be reported as the number of participants with abnormal laboratory values and adverse events related to treatment.
Change: Number of Participants With Treatment-Related Adverse Events as Assessed by Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 for Neurological status
Change in the subject's acute neurologic status will be monitored hourly for 4 hours after infusion. Data recorded include Glasgow Coma Scale (GCS) from infusion to discharge. Grade 3 Central Nervous System (CNS) event as defined in the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 occurring within 12 hours of cellular product infusion will trigger the stopping rules. Other changes temporally related to infusion (those events occurring within 12 hours of infusion) will be considered associated with the protocol and recorded as an adverse event. This will be reported as the number of participants with adverse events related to treatment.
Incidence of Treatment-Emergent Adverse Events for Pulmonary Status
Blood-oxygen saturation will be monitored by finger oximeter. Moderate respiratory dysfunction within the first 24 hours post infusion will be considered an adverse event but will not warrant stopping the trial unless recommended by the Data Safety Monitoring Board. In the event of pulmonary dysfunction, standard supportive therapy will be given. Pulmonary symptoms/events corresponding to the Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 Grade 3 will trigger the stopping rules

Secondary Outcome Measures

Auditory Brainstem Response
Audiometry, to-acoustic emissions and Auditory Brainstem Response will be used to assess the physiologic integrity of the neural structures which are critical to normal audition and speech. Changes in these areas will be evaluated by repeating the measures all follow-up visits.

Full Information

First Posted
August 19, 2015
Last Updated
March 16, 2022
Sponsor
James Baumgartner, MD
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1. Study Identification

Unique Protocol Identification Number
NCT02616172
Brief Title
Autologous Bone Marrow Harvest and Transplant for Sensorineural Hearing Loss
Official Title
Safety of Infusion of Autologous Human Bone Marrow Mononuclear Fraction in Children With Sensorineural Hearing Loss
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Suspended
Why Stopped
Restructuring Cell Lab
Study Start Date
October 2015 (undefined)
Primary Completion Date
September 2022 (Anticipated)
Study Completion Date
September 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
James Baumgartner, MD

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Autologous human bone marrow mononuclear fraction (BMMF) will be harvested and given to children with bilateral moderate to severe sensorineural hearing loss. The aim is to determine if bone marrow mononuclear fraction (BMMF) infusion is safe, feasible, improves inner ear function, audition, and language development.
Detailed Description
Autologous human bone marrow mononuclear fraction (BMMF) will be given to children with bilateral moderate to severe sensorineural hearing loss. Subjects will come to Orlando for pretesting to include an Magnetic Resonance Imaging (MRI), Auditory brainstem response (ABR), blood work: Complete metabolic panel (CMP), Complete blood count (CBC), Hepatic Function Panel, Prothrombin (PT), Partial thromboplastin time (PTT), International normalized ration (INR), Chest Xray, and a Speech and Language Evaluation. After pretesting, the subjects will undergo a bone marrow harvest and then receive their autologous bone marrow mononuclear fraction (BMMF) intravenously. The subjects will then be monitored for 24 hours post infusion. After 24 hours, the subject will undergo repeat blood work and a chest x ray. Subjects will then be discharged home. Subjects will follow up in Orlando at 1 month, 6 months and 1 year post infusion. Follow up testing will repeat the exams performed at pretesting.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sensorineural Hearing Loss

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Autologous bone marrow infusion
Arm Type
Experimental
Arm Description
One time administration of autologous bone marrow mononuclear cells intravenously, minimum dose of 6 million cells per kg Total nucleated cells.
Intervention Type
Genetic
Intervention Name(s)
Autologous Bone Marrow Infusion
Other Intervention Name(s)
Cell based therapy
Intervention Description
The subjects autologous bone marrow cells harvested at Florida Hospital will be infused intravenously by gravity
Primary Outcome Measure Information:
Title
physiological parameter: Blood Pressure
Description
Assessing change from baseline systolic blood pressure to post stem cell infusion systolic blood pressure. The metric for summarizing measurements is millimeters of mercury.
Time Frame
Change from baseline to 24 hours after stem cell infusion
Title
physiological parameter: Pulmonary Endothelial Damage
Description
Measured by the number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Time Frame
Change from baseline to 24 hours post infusion
Title
Change: Number of Participants With Treatment-Related Adverse Events as Assessed by Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 for Hepatic Injury
Description
The reticuloendothelial system can sequester immature blood elements, theoretically resulting in hepatic injury. An acute elevation of the aspartate transaminase (AST) and Alanine Aminotransferase test (ALT) hepatic enzymes >5.0 - 20.0 x upper limit normal (ULN) in the first 24 hours post infusion will trigger the stopping rules. This level corresponds to the Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 Grade 3 adverse event. It is unlikely that "end vessel" microthrombosis would occur in the liver due to the dual blood supply of the liver and the lung is the first pass organ. This will be reported as the number of participants with abnormal laboratory values and adverse events related to treatment.
Time Frame
Change from baseline to post infusion day 1
Title
Change: Number of Participants With Treatment-Related Adverse Events as Assessed by Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 for Neurological status
Description
Change in the subject's acute neurologic status will be monitored hourly for 4 hours after infusion. Data recorded include Glasgow Coma Scale (GCS) from infusion to discharge. Grade 3 Central Nervous System (CNS) event as defined in the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 occurring within 12 hours of cellular product infusion will trigger the stopping rules. Other changes temporally related to infusion (those events occurring within 12 hours of infusion) will be considered associated with the protocol and recorded as an adverse event. This will be reported as the number of participants with adverse events related to treatment.
Time Frame
Change in baseline to 1 day post infusion
Title
Incidence of Treatment-Emergent Adverse Events for Pulmonary Status
Description
Blood-oxygen saturation will be monitored by finger oximeter. Moderate respiratory dysfunction within the first 24 hours post infusion will be considered an adverse event but will not warrant stopping the trial unless recommended by the Data Safety Monitoring Board. In the event of pulmonary dysfunction, standard supportive therapy will be given. Pulmonary symptoms/events corresponding to the Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 Grade 3 will trigger the stopping rules
Time Frame
Baseline to 24 hours after infusion
Secondary Outcome Measure Information:
Title
Auditory Brainstem Response
Description
Audiometry, to-acoustic emissions and Auditory Brainstem Response will be used to assess the physiologic integrity of the neural structures which are critical to normal audition and speech. Changes in these areas will be evaluated by repeating the measures all follow-up visits.
Time Frame
Baseline, 1 month, 6 months, and 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Evidence of sensorineural hearing loss that is, Bilaterally Moderate or Profound in degree Symmetrical or asymmetrical configuration Sudden or progressive in presentation Normally shaped cochlea, as determined by Magnetic Resonance Imaging or computed tomography (CT) The loss must be considered: Acquired Unknown with genetic testing negative. (Genetic testing is not required for Cytomegalovirus (CMV) positive children due to Cytomegalovirus (CMV) known to be number one cause of hearing loss) Fitted for hearing aids no later than six months post detection of loss unless not recommended by treating audiologist or physicians Enrollment in a parent/child intervention program Age 2 years - 6 years old at time of infusion with 2 to 4 years of time elapsed since diagnosis of hearing loss at the time of bone marrow mononuclear fraction (BMMF) infusion. Ability of the child and caregiver to travel to Orlando, and stay for at least 4 days, and to return for all follow-up visits. Exclusion Criteria: Inability to obtain all pertinent medical records: (pertinent physician notes, speech language pathology notes, laboratory findings, test results and imaging studies-must be sent to the research team at least prior to the subject arriving at the study location for preliminary screening and eligibility assessment, preferably14 days before the scheduled visit.) Known history of: Recently treated (ear or any infections) infection less than 2 weeks before infusion. Renal disease of altered renal function as defined by serum creatinine > 1.5 mg/dl at admission. Hepatic disease or altered liver function as defined by Alanine Transaminase (SGPT) > 150 U/L, and or Total Bilirubin > 1.3 mg/dL Malignancy Immunosuppression as defined by White Blood Cell (WBC) < 3,000 at admission Human Immunodeficiency Virus (HIV) Hepatitis B Hepatitis C Pneumonia, or chronic lung disease requiring oxygen Any evidence of active maternal infection during the pregnancy Participation in a concurrent intervention study Mild hearing loss with no evidence of moderate of severe loss Unwillingness or inability to stay for 4 days following infusion (should problems arise following the infusion) and to return for the one month, six month and one year follow-up visits. Evidence of conductive hearing loss Documented recurrent middle ear infections which are frequent (>5 per year) Otitis media at the time of examination Before 2 years from identification of hearing loss at time of infusion After 4 years from identification of hearing loss at time of infusion Diagnosis of the following syndromic cause for hearing loss CHARGE Waardenburg Brachio-Oto-Renal Pendred Alport Treacher-Collins Usher Stickler Syndrome
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Baumgartner, MD
Organizational Affiliation
AdventHealth
Official's Role
Principal Investigator
Facility Information:
Facility Name
Florida Hospital for Children
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Autologous Bone Marrow Harvest and Transplant for Sensorineural Hearing Loss

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