Clinical trial NCT02903355: Phase 3 Clinical Trial: D-methionine to Reduce Noise-Induced Hearing Loss (NIHL)
Official title: Phase 3 Clinical Trial: D-methionine to Reduce Noise-Induced Hearing Loss (NIHL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Noise-induced Hearing Loss
Lead sponsor: Southern Illinois University
Sponsor class: OTHER
First posted: 2016-09-16
Enrollment: 351
Sex: ALL
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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:

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).

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).

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).

Eligibility criteria: Inclusion criteria:

Male or female 21 to 45 years of age Negative pregnancy test at enrollment and prior to taking study drug Willing to use an effective method of birth control during the study (Both male and female participants should avoid pregnancy during study) 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 Willing to refrain from using supplements containing or derived from protein while participating in this study Ability to comply with all study requirements

Exclusion criteria:

History of allergic or idiosyncratic reaction to methionine, amino acid mixtures, nutritional supplements, egg white, or other proteins or food additives Vegetarian (Individual excludes meat and fish from their diet) History of chronic balance disorders 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 Treatment with intravenous (IV) antibiotics within the past 6 months Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug Treatment for alcohol or substance abuse within past 6 months Women of childbearing age who are not using effective contraceptive methods and who may become pregnant during the course of the study Women who are pregnant or breastfeeding. National Guardsmen History of psychotic schizophrenia Exposure within the previous 6 months to systemic ototoxic substances including aminoglycosides or vancomycin Body weight exceeding 225 pounds Renal impairment measured as eGFR \< 50 on screening creatinine clearance blood draw.

Primary outcomes:
measure: ASHA Shift Ear (Left)
timeFrame: Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).
measure: ASHA Shift Ear (Right)
timeFrame: Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).
measure: ASHA Shift Ear (Either)
timeFrame: Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).
measure: ASHA Shift Ear (Both)
timeFrame: Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).
measure: ASHA Shift Ear (Trigger Hand)
timeFrame: Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).
measure: ASHA Shift Ear (Non-Trigger Hand)
timeFrame: Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).
Secondary outcomes:
measure: DOEHRSHC Shift
timeFrame: Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).
measure: EWS STS Shift
timeFrame: Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).
measure: Total THI Score Change
timeFrame: Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).
measure: Significant Change in Tinnitus
timeFrame: Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).
Other outcomes:
Locations:
city: Fort Jackson
country: United States
facility: Moncrief Army Community Hospital
state: South Carolina
Study officials:
affiliation: MetArmor, Inc.
name: Kathleen Campbell, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: United States Department of Defense, US Army Ft. Jackson, South Carolina
name: CPT William Grimes, MD
role: STUDY_DIRECTOR
References: