None listed
Conditions
Brief summary
The purpose of this unblinded, non-randomized, phase I/II trial in patients who require a cochlear implant, is to evaluate the safety and efficacy of localised cochlear neurotrophin gene therapy, by comparing patients receiving a cochlear implant (control group) and patients receiving the gene therapy in conjunction with the cochlear implant (treatment group). The study of the control and treatment groups will not be conducted in parallel because of the logistics around the audiometric assessment of the subjects, which requires extension of the study across a two-year time frame. All subject measures will be identical for both groups, as well as all trial procedures, apart from the treatment and surgical procedures surrounding the delivery of the neurotrophin-encoding DNA to the cochlea, which is an amendment to the normal cochlear implant surgery protocol. For the treatment group, at surgery, prior to insertion of the cochlear implant electrode array into the patient’s cochlea, a cochlear gene delivery electrode array is inserted, naked DNA is injected and then a brief train of electrical pulses lasting less than one second is used to deliver the DNA locally to the cells closest to the electrodes. DNA dispersed through the cochlear tissue, but outside this local electric field, is not taken up by cells and degrades. This somatic cell gene electrotransfer process adds about fifteen minutes to the surgery time. The cochlear gene delivery electrode array is withdrawn after the DNA delivery (BaDGE process) and the cochlear implant itself is then implanted as normal. Participants will be enrolled in the trial for a total of 52 weeks. Data will be collected in the form of completed case record forms, blood tests, questionnaires and adverse events, alongside audiological measurements. Subjects will be followed up at multiple centres for the duration of the trial. They will be recruited from NextSense, cochlear implant surgery will take place at the Royal Prince Alfred Hospital (Sydney), and follow-up visits will take place at both the Australian Hearing Hub (Macquarie University) and NextSense.
Interventions
This Trial Involves the use of a Medical Device, is comparator controlled, and involves gene therapy. It is a multicentre trial. The gene therapy is based on delivery of naked DNA encoding neurotrophins (Brain-derived neurotrophic factor and Neurotrophin-3) which promote regrowth of the auditory nerve. The DNA is transferred to target cells in the cochlea during the cochlear implant procedure using electrotransfer via a modified cochlear implant electrode array. This delivery device is a single
This Trial Involves the use of a Medical Device, is comparator controlled, and involves gene therapy. It is a multicentre trial. The gene therapy is based on delivery of naked DNA encoding neurotrophins (Brain-derived neurotrophic factor and Neurotrophin-3) which promote regrowth of the auditory nerve. The DNA is transferred to target cells in the cochlea during the cochlear implant procedure using electrotransfer via a modified cochlear implant electrode array. This delivery device is a single use device. Following the delivery of the DNA the surgical procedure of the cochlear implant continues as per routine practice. This is a phase I/II trial where 15 cochlear implant recipients receive the neurotrophin gene therapy and in addition 15 subjects are a comparator group who receive the identical cochlear implant device but no gene therapy. The read out is a series of audiometric studies over 12 months. A typical cochlear implant surgical procedure is approximately 2 hours and the gene therapy protocol will increase this by approximately fifteen minutes. The surgeon performing the cochlear implant surgery will delivery the DNA therapy, aided by technical assistance remote from the patient.
Sponsors
UNSW Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
21 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Informed consent is obtained before any trial-related activities are performed (trial-related activities are any procedure/s that would not have been performed during the normal management of the subject) 2. Male or female, aged 21 to 85 years old, inclusive. 3. Mobile, able, and willing to participate in the study. 4. Subjects with severe to profound bilateral hearing loss of less than thirty years. Pure tone audiometric thresholds of greater than or equal to 70 dB HL for each testable octave frequency from 250 Hz through to 8 kHz and CNC sentence recognition scores less than or equal to 80%, or word scores less than or equal to 50%. Subject responses will be monitored for vibrotactile sensation, particularly for the low-frequency stimuli (e.g. 250 Hz). A frequency that elicits vibrotactile responses at levels below 70 dB HL will be considered "not testable" for hearing threshold and only those frequencies that are testable for hearing threshold will be considered for patient inclusion/exclusion in the study 5. Able to communicate well with the investigator, to understand and comply with the requirements of the study 6. Meet surgical requirements/eligibility 7. Subjects must weigh at least 40 kg to participate in the study, and must have a body mass index (BMI) of less than 45 kg/m2. BMI = Body weight (kg) / [Height (m)]2
Exclusion criteria
1. Patients conditions involving cochlea abnormalities that would prevent the insertion of an array or cause excessive perilymph flow during surgery, as judged by the Principal Investigator (e.g. cochlea aplasia, and bone formation within the cochlea) 2. Patients with severe to profound hearing loss diagnosed within the first five years of life 3. Patients with indication of tympanic membrane or middle ear abnormalities as judged by the Principal Investigator 4. Patients with an existing cochlear implant or past cochlear implant in the candidate study ear 5. Patients with serious concomitant conditions (such as a history of a serious cardiac event, renal impairment, hepatic impairment, major surgery etc.) 6. Patients with pacemakers and defibrillators 7. Patients with concomitant malignant or pre-malignant conditions, excluding treated skin cancers 8. Patients with a condition predisposing to, or with a history of, or experiencing neural line tumours 9. Hearing loss due to any other cause that would not be expected to respond to cochlear implantation, for example central auditory lesions or lack of an auditory nerve 10. Patients who will require ototoxic drugs as routine therapy over the course of the study, such as oncology patients on platinum-based chemotherapy 11. Vestibular disequilibrium which in the opinion of the investigator would be incompatible with planned vestibular assessments. 12. Any contraindication to the planned surgery or anaesthesia as determined by the surgeon or anaesthetist 13. Previous surgery or otologic history in the study ear, as judged by the investigator that would affect the surgical implantation of the cochlear implant 14. Mental incapacity, unwillingness or language barrier precluding adequate understanding of the trial procedure or cooperation with the trial site personnel, as judged by the investigator that may affect their ability to take part in the trial. 15. Pre-operative CNC sentence recognition scores of greater than 50% 16. Females of childbearing potential who are pregnant, breast-feeding, or intend on becoming pregnant within the duration of the study 17. Involvement in any interventional clinical trial within 30 days prior to this trial.
Outcome results
None listed