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A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound

ConditionsCentral Auditory Processing DisorderHearing Impaired (Partially)HearingHearing AbnormalityHearing DisabilityHearing DisorderHearing DisordersHearing Impairment, SensorineuralHearing HandicapHearing ImpairedHearing ImpairmentHearing LossCentral Auditory DiseaseNoise ExposureNoise Induced Hearing LossNoise-Induced Hearing LossSound PerceptionMyelin DegenerationMyelinopathyMyelin IntegrityRemyelinationHidden Hearing LossCocktail Party SkillCocktail Party SyndromeCAPDAge Problem
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age45-65
SponsorUniversity of Colorado, Denver

About this trial

The goal of this clinical trial is to determine the efficacy of Clemastine Fumarate in the presence of engineered sound to treat age-related central auditory processing disorder (CAPD). This disorder impacts 800M patients worldwide, including \~1/3 people over 40 years of age and \~1/2 people over 65, resulting in an inability to hear in noisy environments.

The primary hypothesis this study aims to test is: engineered sound, driving localized neural circuit activity, will enable Clemastine Fumarate to mature Oligodendrocyte cells and thus remyelinate these activated neural circuits. This Localized Oligodendrocyte Optimization Therapy (LOOT) was highly effective in preclinical animal studies so this clinical trial aims to answer if this therapy will translate to humans.

The study is an adaptive design intended to compare the efficacy of the drug in the presence or absence of the engineered sound for improving hearing in noise ability. Trial participants will be tested for hearing thresholds and ability to isolate a sound signal from background noise. If they meet the inclusion criteria, they will be enrolled into one of the four arms of the study and undergo the proposed one-month treatment (drug and sound or respective placebos). After the treatment period, trial participants will be tested again for hearing thresholds and their ability to isolate s sound source of interest from background noise. The hypothesis to be tested in this clinical trial is that the one-month treatment will significantly improve the participant's ability to isolate a sound source of interest from background noise.

The design has four arms, drug+sound, placebo+sound, drug+white noise, and placebo+white noise. Based on our preclinical data, control arms are all expected to show identical results, thus our adaptive design includes interim analyses to allow for dropping of two of the three placebo arms should the preclinical results be replicated as anticipated.

We will also monitor each participant's general health during the duration of the clinical trial, which will be done by performing a number of blood tests, an EKG and a general physical before and after the one-month treatment period. We expect no significant changes since participants will take the drug for the one-month period at dosages already demonstrated safe in several Phase II studies of multiple sclerosis. Similarly, the engineered sound will be listened to for one hour per day during this month at sound intensities well below threshold that might cause noise-induced hearing damage.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Male or female between 45 and 65 years old (middle aged) at the screening/enrollment visit (Visit 1).

Written informed consent obtained from the subject and ability for the subject to comply with the requirements of the study.

bilateral hearing thresholds < 20 dB HL at audiometric frequencies from 250 Hz to 4000 Hz inclusively, with no air-bone gaps > 10 dB.

symmetrical hearing thresholds between the ears through 8000 Hz, defined as <20 dB difference at any single audiometric frequency or < 15 dB difference at 2 or more contiguous frequencies.

Disqualifiers

Any subjects who do not fall under the criteria defined above.

Known sensitivity to clemastine fumarate or other antihistamines of similar composition

Pregnancy or nursing mother as determined objectively with a urine pregnancy test

Lower respiratory tract disease including asthma, or breathing difficulties such as emphysema or chronic bronchitis

Trial design

Design model

Parallel

Treatments tested in this trial

  • Clemastine Fumarate Combined With Engineered Sound

    Combination product

    Treatment Group: Drug: 16.08 mg clemastine fumarate (8.04 mg in the morning and 8.04 mg in the evening) during the first week of the 30 day treatment period, followed by 10.72 mg clemastine fumarate once daily in the evening for the remainder of the 30 day period. Tablets taken with water in morning and evening with or without food. This dosage corresponds to 12 mg clemastine base daily during the first week followed by 8 mg clemastine base daily for the remainder of the 30 day period. This matches dosing proven safe in previous Phase II multiple sclerosis trials. Sound: This medication will be combined with a proprietary engineered acoustic stimulus designed to activate central auditory processing pathways, delivered via provided headphones for 60 minutes daily during the 30-day treatment period. Sound consists of spatially modulated frequency sweeps targeting neural circuits involved in speech-in-noise processing. Participants instructed to listen during quiet, awake periods.

  • Clemastine Fumarate Combined With Pink Noise

    Drug

    Drug and Placebo Sound Group: Drug: 16.08 mg clemastine fumarate (8.04 mg in the morning and 8.04 mg in the evening) during the first week of the 30 day treatment period, followed by 10.72 mg clemastine fumarate once daily in the evening for the remainder of the 30 day period. Tablets taken with water in morning and evening with or without food. This dosage corresponds to 12 mg clemastine base daily during the first week followed by 8 mg clemastine base daily for the remainder of the 30 day period. This matches dosing proven safe in previous Phase II multiple sclerosis trials. Sound: Broadband white noise matched for average intensity to engineered sound. Delivered via provided headphones for 60 minutes daily during the 30-day treatment period. Serves as acoustic control to maintain participant and investigator blinding. Participants instructed to listen during quiet, awake periods.

  • Placebo Drug With Engineered Sound

    Combination product

    Placebo Drug and Engineered Sound Group: Drug: Matching placebo tablets administered orally twice daily during the first week and once daily for the remainder of the 30 consecutive days. Tablets identical in appearance, taste, and smell to active drug. Taken with water in morning and evening with or without food. Sound: This placebo will be combined with a proprietary engineered acoustic stimulus designed to activate central auditory processing pathways, delivered via provided headphones for 60 minutes daily during the 30-day treatment period. Sound consists of spatially modulated frequency sweeps targeting neural circuits involved in speech-in-noise processing. Participants instructed to listen during quiet, awake periods.

  • Placebo - Placebo

    Combination product

    Placebo Drug and Placebo Sound Group: Drug: Matching placebo tablets administered orally twice daily during the first week and once daily for the remainder of the 30 consecutive days. Tablets identical in appearance, taste, and smell to active drug. Taken with water in morning and evening with or without food. Sound: Broadband white noise matched for average intensity to engineered sound. Delivered via provided headphones for 60 minutes daily during the 30-day treatment period. Serves as acoustic control to maintain participant and investigator blinding. Participants instructed to listen during quiet, awake periods.

Treatment groups

344 Participants
are divided into 4 treatment groups
Group A: Treatment GroupExperimental treatment 1 intervention
Group B: Placebo SoundActive comparator 1 intervention
Group C: Placebo DrugPlacebo comparator 1 intervention
Group D: Control Group - Double PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Improvement in hearing-in-noise at 15 degree separation

Measures ability to understand speech in background noise, tested in a sound chamber with speakers arranged in a circle. Participants listen to sentences spoken by a female speaker while 6-person babble noise plays from a speaker 15 degrees away. Test uses Harvard IEEE sentences (5 keywords each) at 60 dB with varying signal-to-noise ratios (SNR). Participants repeat words they hear. An adaptive procedure determines the SNR needed for 40% accuracy (\>2/5 words correct) and 80% accuracy (\>4/5 words correct). Lower SNR values indicate better performance. Primary outcome is change in SNR from baseline to post-treatment (Day 30). This tests central auditory processing, not peripheral hearing, as it requires the brain to separate speech from noise when sounds come from different directions. Analysis uses linear regression comparing treatment groups to placebo for change in SNR, with p\<0.017 considered significant due to multiple endpoints. Success is group-wise improvement of \>3dB.

Time frame
At enrollment and again after intervention (Week 5 or 6)
2

Improvement in hearing-in-noise at 30 degree separation

Measures ability to understand speech in background noise, tested in a sound chamber with speakers arranged in a circle. Participants listen to sentences spoken by a female speaker while 6-person babble noise plays from a speaker 30 degrees away. Test uses Harvard IEEE sentences (5 keywords each) at 60 dB with varying signal-to-noise ratios (SNR). Participants repeat words they hear. An adaptive procedure determines the SNR needed for 40% accuracy (\>2/5 words correct) and 80% accuracy (\>4/5 words correct). Lower SNR values indicate better performance. Primary outcome is change in SNR from baseline to post-treatment (Day 30). This tests central auditory processing, not peripheral hearing, as it requires the brain to separate speech from noise when sounds come from different directions. Analysis uses linear regression comparing treatment groups to placebo for change in SNR, with p\<0.017 considered significant due to multiple endpoints. Success is group-wise improvement of \>3dB.

Time frame
At enrollment and again after intervention (Week 5 or 6)

Secondary outcomes

1

Speech, Spatial, and Qualities questionnaire (SSQ)

Speech, Spatial, and Qualities questionnaire (SSQ) by Gatehouse \& Noble, 2004. Self-report questionnaire assessing speech understanding, spatial hearing, and sound quality in daily life. The evaluation ranges from 0-10 for each item. With higher scores indicating better function.

Time frame
At enrollment and again after intervention (Week 5 or 6)
2

Tinnitus Handicap Inventory [THI]

Newman et al., 1996. 25-item questionnaire measuring tinnitus severity and impact on daily life. Scores range from 0-100 with higher scores indicating greater handicap.

Time frame
At enrollment and again after intervention (Week 5 or 6)
3

Wave III amplitude of the ABR

This physiological measurement is not relevant in the participant's daily life, however, changes in ABR waves will give us valuable insights into the mechanisms of the treatment. ABR will be measured via existing predicate devices and/or with FDA cleared EEG devices and standard auditory stimuli appropriate for measuring auditory brainstem response (ABR) waves. This assessment is non-invasive and involves an electrode placed on appropriate locations of a participants head to record electrophysiologic activity while the patient listens to auditory stimuli such as clicking that stimulates the relevant neural circuits.

Time frame
At enrollment and again after intervention (Week 5 or 6)

Other outcomes

1

Audiological Safety & Eligibility

Auditory function assessments will include: Audiogram, and Distortion product otoacoustic emission (DPOAE) tests. For the audiogram and DPOAE, right, left, and bilateral thresholds will be recorded in the range of 250-8000 Hz. To include subjects or determine if an adverse event (AE) has occured, these measures will verify normal thresholds and symmetrical hearing between the ears. On the bilateral audiogram the normal threshold is \< 21 dB hearing loss in the range of (250-4000 Hz) and no air-bone gaps \>10 dB. Symmetrical hearing will be defined by \<21 dB differences OR any single frequency and \<16 dB difference at 2+ contiguous frequencies. For the DPOAE \<20 dB hearing loss will be defined as normal. Clinician judgement will be used to over-rule exclusion or determination of AE.

Time frame
At enrollment and again after intervention (Week 5 or 6)
2

Participant Journal

A participant journal will be completed during the trial to assess deviations from compliance or other self-reported observations.

Time frame
Journal entries will be recorded daily during intervention and returned upon final evaluation (Week 5 or 6)

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Colorado, Denver

Lead sponsor

Source ClinicalTrials.gov
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