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

Noise-Induced Hearing Loss Clinical Trial

— NIHL  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01345474
• Other study ID #: CAM-SIU-11-002
• Status: Terminated
• Phase: Phase 3
• First received: April 27, 2011
• Last updated: October 2, 2017
• Start date: September 2013
• Est. completion date: September 2016

Study information

• Verified date: October 2017
• Source: MetArmor
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 264
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Deafness
• Hearing Loss
• Hearing Loss, Noise-Induced
• Noise-Induced Hearing Loss

Intervention

Drug:
• D-methionine, oral liquid suspension
Two daily doses of up to 100mg/kg/day of D-met for 18 days

Other:
• Placebo Comparator
Equal volume placebo.

Locations

Country	Name	City	State
United States	Moncrief Army Community Hospital	Fort Jackson	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
MetArmor	United States Department of Defense

Country where clinical trial is conducted

United States, 

References & Publications (3)

Campbell K, Claussen A, Meech R, Verhulst S, Fox D, Hughes L. D-methionine (D-met) significantly rescues noise-induced hearing loss: timing studies. Hear Res. 2011 Dec;282(1-2):138-44. doi: 10.1016/j.heares.2011.08.003. Epub 2011 Sep 6. — View Citation

Campbell KC, Meech RP, Klemens JJ, Gerberi MT, Dyrstad SS, Larsen DL, Mitchell DL, El-Azizi M, Verhulst SJ, Hughes LF. Prevention of noise- and drug-induced hearing loss with D-methionine. Hear Res. 2007 Apr;226(1-2):92-103. Epub 2007 Jan 16. — View Citation

Kopke RD, Coleman JK, Liu J, Campbell KC, Riffenburgh RH. Candidate's thesis: enhancing intrinsic cochlear stress defenses to reduce noise-induced hearing loss. Laryngoscope. 2002 Sep;112(9):1515-32. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pure tone air conduction threshold	Change from baseline in pure-tone thresholds as measured by absolute change and frequency of significant noise-induced threshold shift (STS)	15-16 days after cessation of weapons training
Secondary	Tinnitus scales	Tinnitus questionnaire report of change from baseline in scores for both loudness and annoyance	15-16 days after cessation of weapons training