Safety of Autologous Stem Cell Infusion for Children With Acquired Hearing Loss

There is currently no treatment available to repair/reverse acquired sensorineural hearing loss. Recent experiments using human umbilical cord blood treatment of a mouse and guinea pig models have demonstrated hair cell re-growth following acquired sensorineural loss as well as partial restoration of ABR. Autologous human umbilical cord blood therapy, which has been used for over twenty years, has an excellent safety record. This study will determine if autologous human umbilical cord blood infusion in children with hearing loss is safe and feasible, improves inner ear function, audition, and language development. The patients umbilical cord stem cells collected at birth and stored at Cord Blood Registry will be used for infusion.

• Autologous Stem Cells (Genetic), also known as Cell based therapy: The subjects autologous stem cells banked at Cord Blood Registry will be infused intravenously by gravity.

Primary outcomes

• Safety of Autologous Stem Cell Infusion: Number of Participants With Adverse Events. [1 year]: To determine if autologous human umbilical cord blood (hUBC) infusion in children with hearing loss is safe.
• Feasibility of Autologous Stem Cell Infusion: Number of Participants Who Completed Cord Blood Infusion and 1 Month Follow-up. [1 month]: To determine if autologous human umbilical cord blood (hUBC) infusion in children with hearing loss is feasible.

Secondary outcomes

• Change in Auditory Brainstem Response (ABR) Threshold in Decibels. [Pre-treatment (Baseline), 1,6 & 12 months post-treatment]: ABR Threshold is a measure of the sound necessary to activate transmission through the eighth cranial nerve. Each participant was evaluated before, 1,6 and 12 months after autologous stem cell treatments. For each ear, ABR threshold was measured at 500, 1000, 2000 and 4000 Hz and using "Click" ABR.
• Change in Eight Cranial Nerve Wave 5 Latencies in Miliseconds. [Pre-treatment (Baseline), 1,6 & 12 months post-treatment]: .For each ear, latency was measured at 500, 1000, 2000 and 4000 Hz and using "Click" ABR.
• Change in Standard Language Scores. [Pre-treatment, 6 & 12 months post-treatment]: Preschool Language Scale-5. This test measures language development in infants and children. Standard scores are derived, with a mean of 100 and a standard deviation of 15, to compare a child's performance to their peers. Higher values are associated with better language development.
• Change Fractional Anisotropy in the White Sites Along the Audiotory Pathways [Pre-treatment & 12 months post-treatment]: Fractional anisotropy are arbitrary values generated from the DTI sequences of an MRI scan. Higher values suggest increased integrity of white matter pathways. Responders and nonresponders were evaluated separately. (Define non-responders and responders).Although 11 subjects were enrolled and received an autologous cord blood infusion, three subjects did not complete the entire MRI study protocol and could not be analyzed at study completion. The reasons these subjects did not undergo the second MRI are as follows: Subject 7 dropped out of the study, and Subject 11 underwent bilateral cochlear implantation after the 1-month follow-up. Subject 10 refused testing at 12-month follow-up.

Sex: All, ages: 6 Weeks to 6 Years

Inclusion Criteria:

1. Evidence of a sensorineural hearing loss

   * Unilateral or bilateral in configuration
   * Symmetrical or asymmetrical configuration
   * Sudden or progressive in presentation
   * Moderate to profound in degree (40-90 Decibels (dB) in at least one ear
2. Normally shaped cochlea, as determined by MRI
3. The loss must be considered:

   * Acquired
   * Unknown with a negative genetic test.
4. Fitted for hearing aids no later than six months post detection of loss.
5. Enrollment in a parent/child intervention program
6. Age 6 weeks - 6 years old at time of infusion with less than 18 months of hearing loss at the time of cord blood 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 hUBC treatment.)
2. Known history of:

   * Recently treated 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 SGPT > 150 U/L, and or T. Bilirubin > 1.3 mg/dL
   * Malignancy
   * Immunosuppression as defined by WBC < 3,000 at admission
   * Human Immunodeficiency Virus (HIV)
   * Hepatitis B
   * Hepatitis C
   * Evidence of an extensive stroke (> 100ml lesion)
   * Pneumonia, or chronic lung disease requiring oxygen
   * Genetic syndromic sensorineural hearing loss
3. hUBC sample contamination
4. Banked cord cells totaling less than 6x106 mononuclear cells/kilogram body weight.
5. Evidence of the following maternal infections during the pregnancy (Hepatitis A, Hepatitis B, Hepatitis C, HIV 1, HIV 2, Human T-lymphotropic Virus (HTLV) 1, HTLV 2 (CMV and Syphilis can be included in the study)
6. participation in a concurrent intervention study
7. Unwillingness or inability to stay for 4 days following hUBC infusion (should problems arise following the infusion) and to return for the one month, six month and one year follow-up visits.
8. Presence of a cochlear implantation device
9. Evidence of a genetic syndrome
10. Evidence of conductive hearing loss
11. Documented recurrent middle ear infections which are frequent (>5 per year)
12. Otitis media at the time of examination
13. Sensorineural loss is mild
14. Over 18 months from identification of hearing loss at time of infusion

Participant flow

Outcome results

• Safety of Autologous Stem Cell Infusion: Number of Participants With Adverse Events. (Primary), Count of participants, Participants: Autologous Stem Cells 0
• Feasibility of Autologous Stem Cell Infusion: Number of Participants Who Completed Cord Blood Infusion and 1 Month Follow-up. (Primary), Count of participants, Participants: Autologous Stem Cells 11
• Change in Auditory Brainstem Response (ABR) Threshold in Decibels. (Secondary), Mean, decibels: Autologous Stem Cells-Baseline 59.09 +/- 27.00; Autologous Stem Cells-1 Month Post-treatment 47.27 +/- 23.60; Autologous Stem Cell-6 Months Post-treatment 50.91 +/- 23.86; Autologous Stem Cell-12 Months Post-treatment 47.78 +/- 23.06
• Change in Eight Cranial Nerve Wave 5 Latencies in Miliseconds. (Secondary), Mean, milliseconds: Autologous Stem Cells-Baseline 1.33 +/- 0.09; Autologous Stem Cells-1 Month Post-treatment 1.38 +/- 0.08; Autologous Stem Cell-6 Months Post-treatment 1.53 +/- 0.42; Autologous Stem Cell-12 Months Post-treatment 1.26 +/- 0.17
• Change in Standard Language Scores. (Secondary), Mean, units on a scale: Autologous Stem Cells 2.4 +/- 9.8
• Change Fractional Anisotropy in the White Sites Along the Audiotory Pathways (Secondary), Mean, unitless: Autologous Stem Cells 0.2 +/- 0.05

Adverse events

Time frame: 1 year

• James Baumgartner, MD, Principal investigator, AdventHealth