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

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ClinicalTrials.gov Identifier: NCT01345474
Recruitment Status : Terminated
First Posted : May 2, 2011
Last Update Posted : October 3, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Noise-Induced Hearing Loss Drug: D-methionine, oral liquid suspension Other: Placebo Comparator Phase 3

Detailed Description:

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).

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 264 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase 3 Clinical Trial: D-methionine to Reduce Noise-Induced Hearing Loss (NIHL)
Study Start Date : September 2013
Primary Completion Date : September 2016
Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo contains sorbitol, orange flavor and purified water; is flavor and color matched to D-Met.
Other: Placebo Comparator
Equal volume placebo.
Experimental: D-methionine, oral liquid suspension
D-methionine liquid suspension also contains sorbitol, orange flavor and purified water
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


Outcome Measures

Primary Outcome Measures :
  1. Pure tone air conduction threshold [ Time Frame: 15-16 days after cessation of weapons training ]
    Change from baseline in pure-tone thresholds as measured by absolute change and frequency of significant noise-induced threshold shift (STS)


Secondary Outcome Measures :
  1. Tinnitus scales [ Time Frame: 15-16 days after cessation of weapons training ]
    Tinnitus questionnaire report of change from baseline in scores for both loudness and annoyance


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01345474


Locations
United States, South Carolina
Moncrief Army Community Hospital
Fort Jackson, South Carolina, United States, 29207-5700
Sponsors and Collaborators
MetArmor
United States Department of Defense
Investigators
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
More Information

Publications:
Responsible Party: MetArmor
ClinicalTrials.gov Identifier: NCT01345474     History of Changes
Other Study ID Numbers: CAM-SIU-11-002
First Posted: May 2, 2011    Key Record Dates
Last Update Posted: October 3, 2017
Last Verified: October 2017

Keywords provided by MetArmor:
noise-induced hearing loss
hearing loss
tinnitus
weapons training
hearing protection
impulse noise

Additional relevant MeSH terms:
Hearing Loss
Deafness
Hearing Loss, Noise-Induced
Hearing Loss, Sensorineural
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms