Clinical trial NCT06477354: ACEMg Hearing Preservation and Tinnitus Relief
Official title: ACEMg (Soundbites) Hearing Preservation and Tinnitus Relief Otology Intervention Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sensorineural Hearing Loss
Tinnitus
SNHL
Inner Ear Hearing Loss
Keywords: Phase IV open-label post-marketing surveillance
Hearing preservation
Tinnitus
SNHL
Hearing preventive care
ACEMg
Nutraceutical
Real-world data (RWD) analysis
Soundbites
Tinnitus symptom refief
Lead sponsor: Keep Hearing, Inc.
Sponsor class: OTHER
First posted: 2024-06-27
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, post-marketing surveillance
Primary purpose: PREVENTION

Brief summary: ACEMg (Soundbites) is a neuroprotectant dietary supplement designed to block the initiating biological events in the inner ear leading to sensorineural hearing loss, SNHL, which accounts for more than 90% of all hearing loss. SNHL is so common it is called hearing loss. There is no cure for SNHL.

The 24-week OTIS Study aims to validate findings from the previous two-year real-world study demonstrating ACEMg (Soundbites) preserved or improved auditory function (hearing) for 75.3% of participants who used it daily, with most improvement occurring within six months. Additionally, the study aims to assess the potential of ACEMg to relieve tinnitus symptoms in people with tinnitus. SNHL and tinnitus are related, but tinnitus relief was not measured in the previous two-year study.

The OTIS study aims to answer two questions. First, does the real-world data demonstrate that hearing loss is stabilized or improved at the end of the test among participants with sensorineural hearing loss (SNHL or inner ear hearing loss) at the beginning? Second, do participants who self-report tinnitus symptoms at the start of their test report reduced symptoms at the end?

Participants must be eighteen years of age and older and self-report hearing loss and/or tinnitus. The study is conducted at home using a smartphone app and a web-based assessment and data reporting tool developed for this study.

The study starts with a baseline hearing assessment. Participants with tinnitus complete a baseline tinnitus survey. Then, each participant takes ACEMg softgel capsules daily, repeating the hearing assessment and the tinnitus survey after about 12 and 24 weeks. Assessment scores at the beginning of the study will be compared with scores at the end.

Participation in the study is free.

Detailed description: OVERVIEW

The 2-year Soundbites Real World Evidence study used otoacoustic emissions examinations conducted by an audiologist to assess auditory function objectively. Soundbites was clinically proven to preserve or improve hearing for 75.3% of those who took it daily. Among those who benefited, hearing loss stopped for half and improved for the other half. Most of the benefits happened within the first 6 months. Results continued with ongoing use.

ACEMg and tinnitus

ACEMg was not designed to address tinnitus, and the 2-year study did not assess tinnitus. Nevertheless, since ACEMg became available as Soundbites softgel capsules in 2017, reports from customers with tinnitus and from audiologists treating patients with tinnitus indicate that ongoing daily use of Soundbites relieves tinnitus symptoms for some.

Assessing ACEMg for tinnitus symptom relief

An effective cure for tinnitus does not exist. However, research indicates that often, the initial step in tinnitus development is damage to outer hair cells in the cochlea, precisely what ACEMg is designed to block.

That is the rationale for including tinnitus assessments in this follow-on OTIS Study. Many studies aim to reduce the cognitive impacts of permanent, chronic tinnitus by employing various brain training techniques. The OTIS Study is believed to be the first aiming to assess the potential of a clinically proven inner ear neuroprotectant to relieve tinnitus symptoms directly. We hypothesize that a cochlear neuroprotectant intervention may relieve tinnitus symptoms for some.

Who can participate?

The study is open to those eighteen years and older who self-report hearing loss and/or tinnitus and have not used ACEMg as Soundbites.

The study aims to answer two questions.

First, does the real-world data demonstrate that hearing loss is stabilized or improved at the end of the test among participants with SNHL at the beginning? Second, do participants who self-report tinnitus symptoms at the start of their test report reduced symptoms at the end?

How the study works.

The OTIS Study is a collaboration between Keep Hearing Initiative (Keep Hearing), the study sponsor, and Soundbites Public Benefit Corporation (Soundbites PBC). Keep Hearing is responsible for IRB compliance, data analysis, and public health reporting. Soundbites PBC donates the ACEMg test product and is responsible for data collection. Both partners are responsible for recruitment, enrollment, and data security.

Participants conduct the study at home and report their data online using a secure, automated web-based tool developed specifically for the OTIS Study. The study starts with a baseline hearing assessment. Participants with tinnitus also complete a baseline tinnitus survey. Then, each participant takes ACEMg softgel capsules daily, repeating the hearing assessment and the tinnitus survey after about 11 and 24 weeks. Assessment scores at the beginning of the study will be compared with scores at the end.

BACKGROUND OF THE INTERVENTION

ACEMg, developed at the University of Michigan Medical School, is designed to block the initiating biochemical events in the organ of Corti within the inner ear leading to sensorineural hearing loss (SNHL).

The ACEMg formula is classified as Generally Regarded as Safe (GRAS) by the U.S. Pharmacopeia and regulated as a dietary supplement under FDA DSHEA law. The ACEMg patents are licensed to Soundbites Public Benefit Corporation (PBC), which produces an updated and improved oral softgel capsule dose format of ACEMg for adults, and an oral twist-off softgel capsule format for children, available to the public without a prescription under the Soundbites trademark.

PREVIOUS REAL-WORLD EVIDENCE RESEARCH

The 2021-2023 ACEMg (Soundbites) Real-world Evidence Study (N=190) used de-identified real-world data (RWD) from routine annual otoacoustic emissions (OAE) examinations collected among adult patients of one audiology practice over many years before ACEMg became available. OAE examinations produce objective measures of inner ear auditory function.

The control dataset (N=97) represented the current standard of care for hearing, which is to say no treatment. Retrospective OAE RWD from the no-treatment group was analyzed and compared to RWD from a treatment group of patients (N=93) who also had at least two years of annual retrospective OAE examinations and began taking ACEMg immediately following their third annual OAE examination, thus enabling objective measurement of the potential impacts on auditory function from daily oral self-administration of ACEMg.

The study yielded statistically significant clinical data demonstrating that ACEMg effectively preserved and improved auditory function, thereby mitigating SNHL, demonstrating that ACEMg preserved or improved inner ear auditory function for 75.3% (N=70) of those in the treatment group (N=93), with most improvement occurring within the first six months of daily use.

The article reporting results from the study is available on the Open Science Framework (OSF) preprint server at https://osf.io/preprints/osf/uw7tq.

Study administrators concluded that the clinical data justify a larger study, especially considering the inherent safety of ACEMg and its availability in an inexpensive, convenient oral dose form, perhaps leading to considering ACEMg as an effective, accessible method of addressing the global public health challenge of hearing loss.

THE OTIS STUDY

Objectives

1. The study aims to validate findings from the two-year study that ACEMg stabilizes or improves auditory function in those with SNHL and assess the potential impact of ACEMg on tinnitus symptoms, which the two-year study did not assess.
2. The study tests the hypothesis that ACEMg may relieve tinnitus symptoms. ACEMg was not designed to address tinnitus. Nevertheless, since ACEMg was offered as Soundbites softgels in 2017, reports from customers with tinnitus and from audiologists treating patients with tinnitus indicate that ongoing daily use of Soundbites reduces tinnitus symptoms for some.

An effective cure for tinnitus does not yet exist, as our understanding of tinnitus pathophysiology is still evolving. There appear to be multiple neurophysiological mechanisms involved in the production of tinnitus symptoms. A few models, notably the stochastic resonance model, point to a feedback function in the inner ear that increases metabolic stress and cochlear metabolic load, resulting in cochlear damage believed to be an initial step in tinnitus (Krauss \& Schilling, 2016).

Inclusion and exclusion criteria

Individuals eighteen years or older and self-report hearing loss and/or tinnitus may participate. A personal email account and U.S. mailing address are required.

Individuals younger than eighteen years, those who do not have hearing loss or tinnitus, those who have previously taken Soundbites, and those who cannot take the micronutrients beta carotene, vitamin C, vitamin E or Magnesium are excluded from participating.

Method

All potential participants download, read, review, and discuss the informed consent and data-sharing agreement with the study coordinator. Participants accept the agreement online and begin testing ACEMg as Soundbites softgel capsules at home for 24 weeks about 6 months.

The test starts with a baseline hearing assessment of hearing with the hearWHO digits-in-hearing app developed for the World Health Organization until remote otoacoustic emissions (OAE) test technology becomes available.

The hearWHO app uses digits-in-noise (DIN) technology to check hearing status. The app presents 23 sets of three digits over background noise, and the user identifies the digits spoken. The app uses the responses to estimate the signal-to-noise ratio, which indicates hearing ability. The app tracks the level where 50% of triplets can be recognized, called the speech recognition threshold (SRT).

The hearWHO app is available free to the general public. It is recommended for people who listen to loud music over personal audio devices and can also be used by health workers to screen people for hearing loss. The app is intended for use by people 18 years of age and above and may not provide reliable results for children.

The hearWHO hearing test yields subjective data. The same is true for the pure tone audiometry (PTA) examination, considered the gold standard in audiology. In the PTA examination, tones at varying frequencies and intensities are played through headphones, and the individual indicates whether they can hear the tone. As such, the PTA examination requires a subjective response.

Participants self-reporting tinnitus symptoms complete the tinnitus survey which uses questions selected from the Tinnitus Handicap Inventory to assess the degree to which tinnitus symptoms impact daily activities.

All participant data is private. Data is entered into a private, passcode-protected online tool developed for the study. Data is stored on the Open Science Framework online data store. Collected data is limited to birth date, gender, assessment dates, and assessment scores. Participants record their baseline test scores before starting to take ACEMg as Soundbites softgel capsules for adults daily. The hearing test and/or tinnitus survey are repeated at about 12 and 24 weeks.

Data sharing, analysis and reporting

By accepting the terms of the informed consent and data-sharing agreement upon joining the study, participants agree to submit their de-identified data for analysis and reporting after their 24-week test is complete. All data is shared for secondary analysis and reporting under a data-sharing agreement with the study sponsor, the Keep Hearing nonprofit.

Analysis of each participant's results is shared with each participant immediately upon completion of their individual 24-week study. Aggregated data analyses will be reported in publicly available manuscripts submitted for peer review.

Costs

Participation in the study is free. Soundbites Public Benefit Corporation donates the Soundbites softgel capsules, U.S. delivery costs, and the online data entry and data storage tool.

Eligibility criteria: Inclusion Criteria:

* Tinnitus self-reported at the baseline survey, or
* Hearing loss assessed at the baseline test

Exclusion Criteria:

* No tinnitus self-reported at the baseline survey, or
* No hearing loss assessed at the baseline test
* Previous use of ACEMg (Soundbites)

Primary outcomes:
measure: Subjective measure of preservation or improvement of inner ear auditory function
timeFrame: Time point zero; 12 and 24 weeks.
measure: Tinnitus symptom relief
timeFrame: Time point zero; 12 and 24 weeks.
Secondary outcomes:
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: To enroll, visit the Participate in Public Health Research page on keephearing.org
state: Michigan
Study officials:
affiliation: Keep Hearing, Inc. 501c3
name: Barry Seifer, MFA
role: STUDY_DIRECTOR
References: