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

• ClinicalTrials.gov Identifier: NCT02038972
• Recruitment Status: Completed
• First Posted: January 17, 2014
• Last Update Posted: March 5, 2018
• Sponsor: James Baumgartner, MD
• Collaborator: CBR Systems, Inc.
• Information provided by (Responsible Party): James Baumgartner, MD, AdventHealth

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Sensorineural Hearing Loss	Genetic: Autologous Stem Cells	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety of Autologous Stem Cell Infusion for Children With Acquired Hearing Loss
• Study Start Date: January 2013
• Actual Primary Completion Date: December 11, 2015
• Actual Study Completion Date: January 10, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Autologous Stem Cells; A single dose of intravenously administered autologous hUCB will be done. The minimum acceptable dose will be 6x10 6th mononuclear cells/kilogram body weight. The hUCB reanimation, cell processing and product infusion will occur at Florida Hospital for Children and the Florida Hospital Center for Cellular Therapy.	Genetic: Autologous Stem Cells; The subjects autologous stem cells banked at Cord Blood Registry will be infused intravenously by gravity.; Other Name: Cell based therapy

Outcome Measures

Primary Outcome Measures :

1. Safety of Autologous Stem Cell Infusion [ Time Frame: 1 year ]

   To determine if autologous human umbilical cord blood (hUBC) infusion in children with hearing loss is safe and feasible. Infusion related toxicity as measured by:

   i. hemodynamic instability: An adverse event will be defined as a sustained (> 10 minutes) >20% decrease in MAP.

   ii. acute lung injury: Chest X-ray will be done at baseline and at 1 day post infusion to assess for polymorphonuclear infiltrates iii. hepatic injury/toxicity: Hepatic panel will be performed at baseline and 1 day post infusion. Injury is defined as acute elevation of the AST/ALT hepatic enzymes > 900 U/dl in the first 24 hours post infusion iv. renal injury/insufficiency: CMP will be performed at baseline and 1 day after infusion v. exacerbation of neurological status: defined as a change in Glasgow Coma Scale, pupillary size/reactivity, motor/sensory evaluation of extremities, and seizure activity from infusion to discharge.

Secondary Outcome Measures :

1. Inner Ear Function, Audition, and Language Development [ Time Frame: 1 year ]
   To determine if autologous hUBC transplantation in children with hearing loss improves inner ear function, audition and language development.

Eligibility Criteria

• Ages Eligible for Study: 6 Weeks to 6 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Florida

Florida Hospital

Orlando, Florida, United States, 32803

Sponsors and Collaborators

James Baumgartner, MD

CBR Systems, Inc.

Investigators

• Principal Investigator: James Baumgartner, MD; AdventHealth

More Information

• Responsible Party: James Baumgartner, MD, Primary Investigator, AdventHealth
• ClinicalTrials.gov Identifier: NCT02038972
• Other Study ID Numbers: 434269
• First Posted: January 17, 2014
• Last Update Posted: March 5, 2018
• Last Verified: August 2017

Individual Participant Data (IPD) Sharing Statement:

• 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