title: ACEMg-mediated hearing preservation in cochlear implant patients receiving different electrode lengths (PROHEARING): study protocol for a randomized controlled trial.
abstract: The indications for a cochlear implant (CI) have been extended to include patients with some residual hearing. Shorter and thinner atraumatic electrodes have been designed to preserve the residual hearing in the implanted ear. However, the insertion of the electrode array into the cochlea, with potential mechanical trauma and the presence of this foreign body inside the cochlea, may lead to free radical formation and reduced blood perfusion of the cochlea which can result in the loss of residual hearing.
  
  
  
  In this single-center, randomized, placebo-controlled, double-blind phase II clinical trial the effect of free radical scavengers and a vasodilator on the residual hearing of 140 CI patients will be evaluated. The formulation is composed of β-carotene (vitamin A), ascorbic acid (vitamin C), dl-α-tocopherol acetate (vitamin E) and the vasodilator magnesium (Mg), or ACEMg. Medication is administered twice daily per os for approximately 3 months. The primary measure is based upon the reduction in postoperative low-frequency air-conducted pure-tone thresholds compared to preoperative thresholds in ACEMg-treated patients compared to those of a placebo group. Additionally, the effect of different electrode lengths (20, 24 and 28 mm) is analyzed. Study visits are scheduled 2 days before surgery, at first fitting, which is the adjustment and start of stimulation via CI 4 weeks after surgery and 3, 6, 9 and 12 months after first fitting. The primary endpoint is the air-conduction hearing loss at 500 Hz 3 months after first fitting. Additionally, speech recognition tests, hearing aid benefit in the implanted ear and electrophysiological measurements of implant function are assessed. Since this is a blinded clinical trial and recruitment is still ongoing, data continue to accrue and we cannot yet analyze the outcome of the ACEMg treatment.
  
  
  
  There is an unfulfilled need for new strategies to preserve acoustic hearing in CI patients. This study will provide first-in-man data on ACEMg-mediated protection of residual hearing in CI patients. Performing all surgeries and patient follow-up at one study site improves consistency in diagnosis and therapy and less variability in surgery, audiological test techniques and fitting. This approach will allow investigation of the influence of ACEMg on residual hearing in CI patients.
  
  
  
  The German Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) application number 4039192, was registered on 6 December 2013 with protocol amendment version 3.0 from 19 August 2014. EudraCT number: 2012-005002-22 .
authors: Department of Otolaryngology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. scheper.verena@mh-hannover.de.|Cluster of Excellence Hearing4all, Hannover and Oldenburg, Germany. scheper.verena@mh-hannover.de.
authors: Verena
authors: V
authors: Scheper
authors: Department of Otolaryngology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors: Melanie
authors: M
authors: Leifholz
authors: Hannover Clinical Trial Center, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors: Heiko
authors: H
authors: von der Leyen
authors: Hannover Clinical Trial Center, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors: Miriam
authors: M
authors: Keller
authors: Hannover Clinical Trial Center, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors: Ute
authors: U
authors: Denkena
authors: Institute for Biostatistics, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors: Armin
authors: A
authors: Koch
authors: Institute for Biostatistics, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors: Annika
authors: A
authors: Karch
authors: Kresge Hearing Research Institute, University of Michigan, 4605 Medical Science Unit II, Ann Arbor, MI, 48109-5616, USA.
authors: Josef
authors: J
authors: Miller
authors: Department of Otolaryngology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|Cluster of Excellence Hearing4all, Hannover and Oldenburg, Germany.
authors: Thomas
authors: T
authors: Lenarz
mesh_terms: D001205:Ascorbic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D001301:Audiometry, Pure-Tone; D001302:Audiometry, Speech; D001309:Auditory Threshold / Q000187:drug effects; D002985:Clinical Protocols; D019929:Cochlear Implantation / Q000295:instrumentation*; D003054:Cochlear Implants; D004311:Double-Blind Method; D004338:Drug Combinations; D016166:Free Radical Scavengers / Q000009:adverse effects / Q000627:therapeutic use*; D005858:Germany; D006309:Hearing / Q000187:drug effects*; D006801:Humans; D008274:Magnesium / Q000009:adverse effects / Q000627:therapeutic use*; D019986:Persons with Hearing Disabilities / Q000523:psychology / Q000534:rehabilitation*; D011474:Prosthesis Design; D012107:Research Design; D013067:Speech Perception / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D024502:alpha-Tocopherol / Q000009:adverse effects / Q000627:therapeutic use*; D019207:beta Carotene / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; D016166:Free Radical Scavengers; D014665:Vasodilator Agents; D019207:beta Carotene; D024502:alpha-Tocopherol; D008274:Magnesium; D001205:Ascorbic Acid
keywords: Antioxidants; Cochlear implant; EAS; Electric acoustic stimulation; Free radicals; Hearing preservation; Residual hearing