Phase 3 Clinical Trial: D-methionine to Reduce Noise-Induced Hearing Loss (NIHL) (NIHL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by MetArmor
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
MetArmor
ClinicalTrials.gov Identifier:
NCT01345474
First received: April 27, 2011
Last updated: July 21, 2016
Last verified: July 2016

April 27, 2011
July 21, 2016
September 2013
December 2016   (final data collection date for primary outcome measure)
Pure tone air conduction threshold [ Time Frame: 15-16 days after cessation of weapons training ] [ Designated as safety issue: No ]
Change from baseline in pure-tone thresholds as measured by absolute change and frequency of significant noise-induced threshold shift (STS)
Pure tone air conduction threshold [ Time Frame: 22 days after cessation of weapons training ] [ Designated as safety issue: No ]
Change from baseline in pure-tone thresholds as measured by absolute change and frequency of significant noise-induced threshold shift (STS)
Complete list of historical versions of study NCT01345474 on ClinicalTrials.gov Archive Site
Tinnitus scales [ Time Frame: 15-16 days after cessation of weapons training ] [ Designated as safety issue: No ]
Tinnitus questionnaire report of change from baseline in scores for both loudness and annoyance
  • Tinnitus scales [ Time Frame: 22 days after cessation of weapons training ] [ Designated as safety issue: No ]
    Tinnitus questionnaire report of change from baseline in scores for both loudness and annoyance
  • tympanic membrane function [ Time Frame: 22 days after cessation of weapons training ] [ Designated as safety issue: No ]
    tympanometry measurement report of change from baseline
Not Provided
Not Provided
 
Phase 3 Clinical Trial: D-methionine to Reduce Noise-Induced Hearing Loss (NIHL)
Phase 3 Clinical Trial: D-methionine to Reduce Noise-Induced Hearing Loss (NIHL)
This prospective study is a randomized, double-blind, placebo-controlled Phase 3 clinical trial of oral D-methionine (D-met) to reduce noise-induced hearing loss (NIHL) and tinnitus. The goal of the study is to develop a safe, oral pharmacological agent to augment physical hearing protectors for noise exposures that exceed the protective capabilities of ear plugs and/or muffs. The study population is a cohort of Drill Sergeant (DS) instructor trainees during and 22 days after their 11 day weapons training. The primary objective of this study is to determine the efficacy of D-met in preventing NIHL or reducing tinnitus secondary to a minimum of 500 rounds of M-16 weapons training occurring over an 11 day period.

Hearing loss can render a soldier less able to detect and identify the enemy, less able to understand commands, particularly in background noise typical on the battlefield, and may permanently reduce quality of life. In some cases, hearing loss may preclude redeployment or result in less optimal job assignment. Currently, no FDA approved pharmacological prevention exists for noise-induced hearing loss (NIHL). We have documented in animal studies that administration of D-methionine (D-met) can reduce or prevent NIHL. We now need to determine if it has similar efficacy in humans. Although we have not yet tested D-met on protection from noise-induced tinnitus in animals, this clinical trial would provide us the opportunity to also test for protection from noise induced tinnitus simultaneously.

Objective Hypotheses:

Primary Hypothesis: Administration of oral D-methionine prior to, during and 4 days post-weapons training will reduce or prevent permanent noise-induced hearing loss.

Secondary Hypothesis: Administration of oral D-methionine prior to, during and 4 days post-weapons training will reduce or prevent noise-induced tinnitus.

Specific Aims:

  1. To determine whether administering oral D-met can prevent permanent NIHL after weapons training. This aim will be addressed by comparing the results of D-met versus placebo administration starting 3 days prior to, during the 11 day period of weapons training (Monday-Friday for first week, Monday-Thursday for second week), and 4 days after for a total of 18 days. Pure tone hearing thresholds will be assessed before and 22 days after completion of weapons training (ie; 18 days after the last day of study drug/placebo administration).
  2. To determine whether administering oral D-met can prevent tinnitus after weapons training. This aim will be addressed by comparing the results of D-met versus placebo administration starting 3 days prior to, during the 11 day period of weapons training (Monday-Friday for first week, Monday-Thursday for second week), and 4 days after for a total of 18 days. Tinnitus questionnaires will be assessed before and 22 days after completion of weapons training (ie; 18 days after the last day of study drug/placebo administration).
  3. To monitor for any potential side effects of D-met in human subjects. This aim will be accomplished by subject query on each day study drug is dispensed (twice daily) and at final study visit, routing of any adverse event reports to study medical personnel, statisticians and to the Food and Drug Administration (FDA).
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Noise-Induced Hearing Loss
  • Drug: D-methionine, oral liquid suspension
    Two daily doses of up to 100mg/kg/day of D-met for 18 days
    Other Name: D-met
  • Other: Placebo Comparator
    Equal volume placebo.
  • Placebo Comparator: Placebo
    Placebo contains sorbitol, orange flavor and purified water; is flavor and color matched to D-Met.
    Intervention: Other: Placebo Comparator
  • Experimental: D-methionine, oral liquid suspension
    D-methionine liquid suspension also contains sorbitol, orange flavor and purified water
    Intervention: Drug: D-methionine, oral liquid suspension

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
600
December 2017
December 2016   (final data collection date for primary outcome measure)

Inclusion criteria:

  1. Male or female
  2. 21 to 45 years of age
  3. Negative pregnancy test at enrollment and prior to taking study drug
  4. Willing to use an effective method of birth control during the study (Both male and female participants should avoid pregnancy during study)
  5. Pure tone air conduction threshold average at 0.5, 1 and 2 kHz of no greater than 40 dB HL bilaterally with no air bone gaps greater than 10 dB and normal otoscopy and tympanometry screens
  6. Willing to refrain from using supplements containing or derived from protein while participating in this study
  7. Ability to comply with all study requirements

Exclusion criteria:

  1. History of allergic or idiosyncratic reaction to methionine, amino acid mixtures, nutritional supplements, egg white, or other proteins or food additives
  2. Vegetarian (Individual excludes meat and fish from their diet)
  3. History of chronic balance disorders
  4. Abnormal otoscopic findings, otologic surgery, autoimmune inner ear disease, significant air-bone gaps, abnormal tympanograms or other indication of middle-ear abnormality, history of fluctuant hearing or asymmetric hearing worse than 25 dB at any frequency in either ear, perilymphatic fistula, tumor of the auditory system, or other CNS disorder that is likely to affect hearing
  5. Treatment with intravenous (IV) antibiotics within the past 6 months
  6. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug
  7. Treatment for alcohol or substance abuse within past 6 months
  8. Women of childbearing age who are not using effective contraceptive methods and who may become pregnant during the course of the study
  9. Women who are pregnant or breastfeeding.
  10. National Guardsmen
  11. History of psychotic schizophrenia
  12. Exposure within the previous 6 months to systemic ototoxic substances including aminoglycosides or vancomycin
  13. Body weight exceeding 225 pounds
  14. Renal impairment measured as eGFR < 50 on screening creatinine clearance blood draw.
Both
21 Years to 40 Years   (Adult)
Yes
Contact: Kathleen CM Campbell, PhD 217-545-7310 kcampbell@siumed.edu
Contact: Daniel J Fox, MPH, PhD 217-545-6774 dfox@siumed.edu
United States
 
NCT01345474
CAM-SIU-11-002
Yes
Not Provided
Not Provided
MetArmor
MetArmor
United States Department of Defense
Study Director: MAJ Christopher Wilson, MD, MPH United States Department of Defense, US Army Ft. Jackson, South Carolina
Principal Investigator: Kathleen CM Campbell, CCC-A, PhD Southern Illinois University School of Medicine
MetArmor
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP