Autologous Bone Marrow Harvest and Transplant for Sensorineural Hearing Loss
Sensorineural Hearing Loss
Genetic: Autologous Bone Marrow Infusion
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Safety of Infusion of Autologous Human Bone Marrow Mononuclear Fraction in Children With Sensorineural Hearing Loss|
- physiological parameter: Blood Pressure [ Time Frame: Change from baseline to 24 hours after stem cell infusion ] [ Designated as safety issue: Yes ]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 [ Time Frame: Change from baseline to 24 hours post infusion ] [ Designated as safety issue: Yes ]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 [ Time Frame: Change from baseline to post infusion day 1 ] [ Designated as safety issue: Yes ]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 [ Time Frame: Change in baseline to 1 day post infusion ] [ Designated as safety issue: Yes ]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 [ Time Frame: Baseline to 24 hours after infusion ] [ Designated as safety issue: Yes ]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
- Auditory Brainstem Response [ Time Frame: Baseline, 1 month, 6 months, and 1 year ] [ Designated as safety issue: No ]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.
|Study Start Date:||October 2015|
|Estimated Study Completion Date:||September 2018|
|Estimated Primary Completion Date:||September 2018 (Final data collection date for primary outcome measure)|
Experimental: Autologous bone marrow infusion
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
The subjects autologous bone marrow cells harvested at Florida Hospital will be infused intravenously by gravity
Other Name: Cell based therapy
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02616172
|United States, Florida|
|Florida Hospital for Children|
|Orlando, Florida, United States, 32803|
|Principal Investigator:||James Baumgartner, MD||Florida Hospital|