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

NCT02903355 | Terminated Phase 3 Results DMC

• 1 other identifier: 01345474
• Study Type: interventional
• Target: 351
• Locations: 1 country
• Sites: 1

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.

Conditions

Noise-induced Hearing Loss

Outcome Measures

Primary Outcomes (6)

• ASHA Shift Ear (Left)

  An increase of at least 20 dB at any one frequency, An increase of at least 10 dB at any two consecutive frequencies, or Loss of response at 3 consecutive frequencies where responses were obtained at baseline.

  Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).

• ASHA Shift Ear (Right)

  An increase of at least 20 dB at any one frequency, An increase of at least 10 dB at any two consecutive frequencies, or Loss of response at 3 consecutive frequencies where responses were obtained at baseline.

  Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).

• ASHA Shift Ear (Either)

  An increase of at least 20 dB at any one frequency, An increase of at least 10 dB at any two consecutive frequencies, or Loss of response at 3 consecutive frequencies where responses were obtained at baseline.

  Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).

• ASHA Shift Ear (Both)

  An increase of at least 20 dB at any one frequency, An increase of at least 10 dB at any two consecutive frequencies, or Loss of response at 3 consecutive frequencies where responses were obtained at baseline.

  Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).

• ASHA Shift Ear (Trigger Hand)

  An increase of at least 20 dB at any one frequency, An increase of at least 10 dB at any two consecutive frequencies, or Loss of response at 3 consecutive frequencies where responses were obtained at baseline.

  Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).

• ASHA Shift Ear (Non-Trigger Hand)

  An increase of at least 20 dB at any one frequency, An increase of at least 10 dB at any two consecutive frequencies, or Loss of response at 3 consecutive frequencies where responses were obtained at baseline.

  Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).

Secondary Outcomes (4)

• DOEHRSHC Shift

  Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).

• EWS STS Shift

  Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).

• Total THI Score Change

  Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).

• Significant Change in Tinnitus

  Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo contains sorbitol, orange flavor and purified water; is flavor and color matched to D-Met.

Drug: Placebo

D-methionine, oral liquid suspension

EXPERIMENTAL

D-methionine liquid suspension also contains sorbitol, orange flavor and purified water Intervention: Drug: D-methionine, oral liquid suspension.

Drug: D-methionine

Interventions

D-methionine DRUG

D-methionine, oral liquid suspension

D-methionine, oral liquid suspension

Placebo DRUG

Placebo contains sorbitol, orange flavor and purified water; is flavor and color matched to D-Met.

Placebo

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Southern Illinois University: lead

Study Sites (1)

Moncrief Army Community Hospital

Fort Jackson, South Carolina, 29207, United States

Location

MeSH Terms

Conditions

Hearing Loss, Noise-Induced

Condition Hierarchy (Ancestors)

Hearing Loss, Sensorineural; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gary Fifer, MSHI
• Organization: Southern Illinois University School of Medicine

gfifer@siumed.edu

217-545-7823

Study Officials

• Kathleen Campbell, PhD

  MetArmor, Inc.

  PRINCIPAL INVESTIGATOR

• CPT William Grimes, MD

  United States Department of Defense, US Army Ft. Jackson, South Carolina

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2016
• First Posted: September 16, 2016
• Study Start: September 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: June 28, 2022
• Results First Posted: June 28, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)