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

Phase 3

Terminated

Conditions: Noise-induced Hearing Loss

Interventions: Drug: Placebo
Drug: D-methionine

Registration Number: NCT02903355

Lead Sponsor: Southern Illinois University

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).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 351

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo contains sorbitol, orange flavor and purified water; is flavor and color matched to D-Met.
D-methionine, oral liquid suspension	D-methionine	D-methionine liquid suspension also contains sorbitol, orange flavor and purified water Intervention: Drug: D-methionine, oral liquid suspension.

Primary Outcome Measures

Name	Time	Method
ASHA Shift Ear (Left)	Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).	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.
ASHA Shift Ear (Either)	Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).	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.
ASHA Shift Ear (Trigger Hand)	Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).	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.
ASHA Shift Ear (Right)	Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).	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.
ASHA Shift Ear (Non-Trigger Hand)	Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).	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.
ASHA Shift Ear (Both)	Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).	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.

Secondary Outcome Measures

Name	Time	Method
DOEHRSHC Shift	Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).	Greater than or equal to 10 dB change for the average of 2k, 3k, and 4k in either ear. This is a binary outcome measure based on meeting this definition.
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).	An increase of at least 5 points in the Tinnitus Handicap Inventory (THI), AND an increase in one severity grade category (Categories listed below). Tinnitus handicap inventory is designed to evaluate the difficulties experienced as a result of hearing loss. Score ranges from 0 to 100, with 0 indicating no handicap, and 100 indicating catastrophic handicap. The THI score was to compare pre and post treatment effects of hearing loss. 0-16: Slight or no handicap (Grade 1) 18-36: Mild handicap (Grade 2) 38-56: Moderate handicap (Grade 3) 58-76: Severe handicap (Grade 4) 78-100: Catastrophic handicap (Grade 5)
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).	Tinnitus Handicap Inventory. Tinnitus handicap inventory designed to evaluate the difficulties experienced as a result of hearing loss. Score ranges from 0 to 100 with 0 indicating no handicap, and 100 indicating catastrophic handicap. The THI score was to compare pre and post treatment effects of hearing loss.
EWS STS Shift	Change from baseline to day 29-36 after initial administration of study drug (Day 15-22 after cessation of weapons training).	Greater than or equal to 15 dB change (deficit) in any of the following frequencies in either ear (1k or 2k or 3k or 4k). This is a binary outcome measure based on meeting this definition.