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Trial record 2 of 65 for:    Autologous Bone and harvest

Autologous Bone Marrow Harvest and Transplant for Sensorineural Hearing Loss

This study has suspended participant recruitment.
(Restructuring Cell Lab)
Sponsor:
Information provided by (Responsible Party):
Florida Hospital
ClinicalTrials.gov Identifier:
NCT02616172
First received: August 19, 2015
Last updated: August 10, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Sensorineural Hearing Loss
Genetic: Autologous Bone Marrow Infusion
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Florida Hospital:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 10
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)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   2 Years to 6 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02616172

Locations
United States, Florida
Florida Hospital for Children
Orlando, Florida, United States, 32803
Sponsors and Collaborators
Florida Hospital
Investigators
Principal Investigator: James Baumgartner, MD Florida Hospital
  More Information

Responsible Party: Florida Hospital
ClinicalTrials.gov Identifier: NCT02616172     History of Changes
Other Study ID Numbers: 695389 
Study First Received: August 19, 2015
Last Updated: August 10, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Hearing Loss
Deafness
Hearing Loss, Sensorineural
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on September 28, 2016