Sensorineural Hearing Loss
Conditions
Brief summary
To determine if autologous human umbilical cord blood infusion in children with acquired hearing loss is safe, feasible, improves inner ear function, audition and language development.
Detailed description
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.
Interventions
GENETICAutologous Stem Cells
The subjects autologous stem cells banked at Cord Blood Registry will be infused intravenously by gravity.
Sponsors
James Baumgartner, MD
CBR Systems, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Treatment consisted of autologous cord blood mononuclear fraction. Dose was the total nucleated cells delivered intravenously per kilogram of treatment subject weight
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 6 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJames Baumgartner, MD
AdventHealth
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 30.27 months STANDARD_DEVIATION 25.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 11 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
None listed