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

NCT07304024 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-1184
• Study Type: interventional
• Target: 344
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hearing Impaired (Partially); Hearing; Hearing Abnormality; Hearing Disability; Hearing Disorder; Hearing Disorders; Hearing Impairment, Sensorineural; Hearing Handicap; Hearing Impaired; Hearing Impairment; Hearing Loss; Central Auditory Disease; Noise Exposure; Noise Induced Hearing Loss; Noise-Induced Hearing Loss; Sound Perception; Myelin Degeneration; Myelinopathy; Myelin Integrity; Remyelination; Hidden Hearing Loss; Cocktail Party Skill; Cocktail Party Syndrome; CAPD; Age Problem; Central Auditory Processing Disorder

Keywords

clemastine fumarate; Hidden Hearing Loss; Cocktail Party; Engineered Sound; Sound Therapy; central auditory processing disorder; Hearing in noise; oligodendrocyte; Localized Oligodendrocyte Optimization Therapy; LOOT; CAPD; Age-Related Hearing Loss

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

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

Secondary Outcomes (3)

• Speech, Spatial, and Qualities questionnaire (SSQ)

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

• Tinnitus Handicap Inventory [THI]

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

• Wave III amplitude of the ABR

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

Other Outcomes (2)

• Audiological Safety & Eligibility

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

• Participant Journal

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

Study Arms (4)

Treatment Group

EXPERIMENTAL

Active clemastine fumarate + engineered sound stimulation

Combination Product: Clemastine Fumarate Combined With Engineered Sound

Placebo Sound

ACTIVE COMPARATOR

Active clemastine fumarate + placebo sound (white/pink noise)

Drug: Clemastine Fumarate Combined With Pink Noise

Placebo Drug

PLACEBO COMPARATOR

Placebo drug + engineered sound stimulation

Combination Product: Placebo Drug With Engineered Sound

Control Group - Double Placebo

PLACEBO COMPARATOR

Placebo drug + placebo sound (white/pink noise)

Combination Product: Placebo - Placebo

Interventions

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.

Also known as: Dayhist, Tavist

Placebo Sound

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 Drug

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.

Control Group - Double Placebo

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.

Also known as: Localized Oligodendrocyte Optimization Therapy, LOOT

Treatment Group

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Documentation of no more than a mild high-frequency hearing sensitivity loss and normal middle-ear function will be obtained using standard audiometric equipment with measurements done by an audiologist; Specifically, testing will show:
• 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.
• normal (Type A) tympanograms bilaterally.
• No cognitive deficit shown upon screening with the Montreal Cognitive Assessment (MOCA) test (Nasreddine et al. 2005).
• Distortion product otoacoustic emission (DPOAE) showing no more than 20 dB hearing loss at audiometric frequencies from 250 Hz to 4000 Hz.
• Subjects failing the hearing in noise test at 15 degrees. Failing is defined as SNR being 12 dB below from what is found in normal hearing subjects without central hearing loss.

You may not qualify if:

• Any subjects who do not fall under the criteria defined above.
• Any of the following conditions which are listed as contraindications or warnings for use of the clinical trial drug (from labeling):
• 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
• Glaucoma or increased intraocular pressure
• Stenosing peptic ulcers or pyloroduodenal obstruction
• Significant cardiovascular disease, chronic hypertension or hypotension
• Hyperthyroidism
• Alcoholism- as defined by consuming on average 3+ drinks per day for women or 4+ drinks per day for men or previous diagnosis of alcohol use disorder by a clinician as defined by DSM V criteria.
• Patients with a history of seizures will be excluded.
• Patients with evidence of suicidal ideation/behavior as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS).
• Leukopenia as defined as a CBC white blood cell count \< 4000/ul
• Anemia as defined by a CBC Hemoglobin \<9.0 g/dL or \<10.0 g/dL (Grade 2+ CTCAE)
• Lymphopenia as defined by CBC Absolute lymphocyte count \<1000/µL.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Anschutz Medical Center

Aurora, Colorado, 80045, United States

RECRUITING

Related Publications (9)

• Green AJ, Gelfand JM, Cree BA, Bevan C, Boscardin WJ, Mei F, Inman J, Arnow S, Devereux M, Abounasr A, Nobuta H, Zhu A, Friessen M, Gerona R, von Budingen HC, Henry RG, Hauser SL, Chan JR. Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial. Lancet. 2017 Dec 2;390(10111):2481-2489. doi: 10.1016/S0140-6736(17)32346-2. Epub 2017 Oct 10.

  PMID: 29029896 BACKGROUND

• Mei F, Fancy SPJ, Shen YA, Niu J, Zhao C, Presley B, Miao E, Lee S, Mayoral SR, Redmond SA, Etxeberria A, Xiao L, Franklin RJM, Green A, Hauser SL, Chan JR. Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis. Nat Med. 2014 Aug;20(8):954-960. doi: 10.1038/nm.3618. Epub 2014 Jul 6.

  PMID: 24997607 BACKGROUND

• Manousi A, Kury P. Small molecule screening as an approach to encounter inefficient myelin repair. Curr Opin Pharmacol. 2021 Dec;61:127-135. doi: 10.1016/j.coph.2021.09.008. Epub 2021 Nov 6.

  PMID: 34753035 BACKGROUND

• Schran HF, Petryk L, Chang CT, O'Connor R, Gelbert MB. The pharmacokinetics and bioavailability of clemastine and phenylpropanolamine in single-component and combination formulations. J Clin Pharmacol. 1996 Oct;36(10):911-22. doi: 10.1002/j.1552-4604.1996.tb04758.x.

  PMID: 8930778 BACKGROUND

• Cox RM, Alexander GC, Gilmore C. Development of the Connected Speech Test (CST). Ear Hear. 1987 Oct;8(5 Suppl):119S-126S. doi: 10.1097/00003446-198710001-00010.

  PMID: 3678650 BACKGROUND

• Gatehouse S, Noble W. The Speech, Spatial and Qualities of Hearing Scale (SSQ). Int J Audiol. 2004 Feb;43(2):85-99. doi: 10.1080/14992020400050014.

  PMID: 15035561 BACKGROUND

• Killion MC, Niquette PA, Gudmundsen GI, Revit LJ, Banerjee S. Development of a quick speech-in-noise test for measuring signal-to-noise ratio loss in normal-hearing and hearing-impaired listeners. J Acoust Soc Am. 2004 Oct;116(4 Pt 1):2395-405. doi: 10.1121/1.1784440.

  PMID: 15532670 BACKGROUND

• Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

  PMID: 15817019 BACKGROUND

• Newman CW, Jacobson GP, Spitzer JB. Development of the Tinnitus Handicap Inventory. Arch Otolaryngol Head Neck Surg. 1996 Feb;122(2):143-8. doi: 10.1001/archotol.1996.01890140029007.

  PMID: 8630207 BACKGROUND

MeSH Terms

Conditions

Language Development Disorders; Hearing Loss; Hearing Disorders; Hearing Loss, Sensorineural; Auditory Diseases, Central; Hearing Loss, Noise-Induced; Hearing Loss, Hidden; Presbycusis

Interventions

Clemastine; Placebo Effect

Condition Hierarchy (Ancestors)

Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Retrocochlear Diseases; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Effect Modifier, Epidemiologic; Epidemiologic Factors; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Achim Klug, PhD

  Colorado University Anschutz Medical Center

  PRINCIPAL INVESTIGATOR

• Samuel A Budoff, PhD, MS

  Colorado University Anschutz Medical Center

  STUDY DIRECTOR

Central Study Contacts

Ajay Keerthy, BS

CONTACT

248-421-5796; ajay.keerthy@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study coordinators and all study personnel interacting with participants will be masked. The study statistician performing the interim analysis for the adaptive design will remain blinded to treatment allocation, using coded group assignments. A secondary statistician will evaluate study data as it is generated but will not have any contact with assigned participants or influence on study coordinators, care providers, or outcome assessors. Pharmacy staff preparing study medications will not be blinded but will have no participant contact.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Trial participants will be tested for hearing thresholds and ability to isolate a sound signal from background noise. If appropriate, they will then be enrolled into one of the four arms of the study and undergo the proposed one-month treatment. After the treatment period, participants will be tested again for hearing thresholds and their ability to isolate s sound source of interest from background noise. Adaptive parallel design with 4 initial arms. Interim analysis planned to assess whether the three control arms (placebo+sound, drug+white noise, placebo+white noise) show equivalent results as predicted by preclinical data. If confirmed, two control arms may be dropped to optimize study efficiency while maintaining scientific rigor.

Study Record Dates

• First Submitted: December 19, 2025
• First Posted: December 26, 2025
• Study Start: March 31, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)