Autologous Bone Marrow Harvest and Transplant for Sensorineural Hearing Loss

NCT02616172 | Suspended Phase 1 DMC

• 1 other identifier: 695389
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Sensorineural Hearing Loss

Outcome Measures

Primary Outcomes (5)

• 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.

  Change from baseline to 24 hours after stem cell infusion

• physiological parameter: Pulmonary Endothelial Damage

  Measured by the number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

  Change from baseline to 24 hours post infusion

• 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 from baseline to post infusion day 1

• 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.

  Change in baseline to 1 day post infusion

• 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

  Baseline to 24 hours after infusion

Secondary Outcomes (1)

• Auditory Brainstem Response

  Baseline, 1 month, 6 months, and 1 year

Study Arms (1)

Autologous bone marrow infusion

EXPERIMENTAL

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

Genetic: Autologous Bone Marrow Infusion

Interventions

Autologous Bone Marrow Infusion GENETIC

The subjects autologous bone marrow cells harvested at Florida Hospital will be infused intravenously by gravity

Also known as: Cell based therapy

Autologous bone marrow infusion

Eligibility Criteria

• Age: 2 Years - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• James Baumgartner, MD: lead

Study Sites (1)

Florida Hospital for Children

Orlando, Florida, 32803, United States

Location

MeSH Terms

Conditions

Hearing Loss, Sensorineural

Interventions

Cell- and Tissue-Based Therapy

Condition Hierarchy (Ancestors)

Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• James Baumgartner, MD

  AdventHealth

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Primary Investigator

Study Record Dates

• First Submitted: August 19, 2015
• First Posted: November 26, 2015
• Study Start: October 1, 2015
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: March 18, 2022

Record last verified: 2022-03

Locations

US (1)