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Central Auditory Processing DisorderPhase 1/2CAPD-LOOTNCT07304024

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

A Phase 1/2 study testing Clemastine Fumarate Combined With Engineered Sound and Clemastine Fumarate Combined With Pink Noise in people with Central Auditory Processing Disorder and Hearing Impaired (Partially), run by University of Colorado, Denver at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 45 to 65 years
What is being tested?
Clemastine Fumarate Combined With Engineered Sound and Clemastine Fumarate Combined With Pink Noise
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
344 participants
Where
1 siteUnited States
Study dates
31 Mar 2025to Jul 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • 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.

Who cannot join

  • 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
Show all 30Show fewer
  • Stenosing peptic ulcers or pyloroduodenal obstruction
  • Trouble urinating due to an enlarged prostate gland. Mild urinary issues (Stage 1 Benign Prostatic Hyperplasia) will not be considered an automatic exclusion but it must be emphasized to patients with this diagnosis that difficulty urinating is a possible side effect that may compound their BPH symptoms.
  • 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).
  • We will generally exclude subjects with significant or uncontrolled medical disorders (e.g., hepatic, hematologic, renal, gastrointestinal, neurological, psychiatric disorders). We will define these patients as those who fall outside of normal ranges for a physical examination of vital signs, a 12-lead EKG, and a safety clinical laboratory assessment including complete blood count (CBC) and comprehensive metabolic panel (CMP). Exclusion with these tests will specifically focus on identifying the following disorders based on the listed criteria:
  • 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.
  • Neutropenia as defined by CBC ANC <1500/µL (solid tumors), ANC <1000/µL (hematologic malignancies). In the case of participants with African, Middle Eastern or West Indian descent a clinician's judgement will be considered to assess the possibility of benign ethnic neutropenia which is not an exclusion criteria.
  • Thrombocytopenia as defined by CBC Platelet count <75000/µL
  • Hepatic Impairment based on CMP: Total bilirubin >1.5× ULN, AST/ALT >3× ULN (or >5× ULN if liver metastases), Alkaline phosphatase >3× ULN.
  • Hepatic Impairment based on CMP: Serum creatinine >2.0 mg/dL (alternative threshold).
  • Metabolic abnormalities based on CMP: Albumin <3.0 g/dL
  • Taking medications that would contraindicate taking the clinical trial drug; Specifically, (from labeling):
  • Monoamine oxidase inhibitor therapy
  • CNS depressants (sedatives, tranquilizers, hypnotics)
  • A history of significant otologic disorder such as repetitive ear infections or Meniere's disease
  • A history of significant neurologic disorder, or current neurodegenerative diseases such as multiple sclerosis, which could present a confound and impact the electrophysiological outcome measures.
  • A history of traumatic brain or closed head injury because this can cause symptoms of central auditory processing problems unrelated to aging and demyelination.
  • English as a second language (non-native English speakers), which is known to negatively impact scores on speech recognition testing.
  • Presence of any other condition or abnormality that in the opinion of the Investigator or his co-PIs would compromise the safety of the patient or the quality of the data.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ajay Keerthy, BS contact

248-421-5796

ajay.keerthy@cuanschutz.edu

United States1 site, 1 recruiting

  • University of Colorado Anschutz Medical Center

    Aurora, Colorado, 80045

    Achim Klug, PhD, 303-724-4621, achim.klug@cuanschutz.edu

    Samuel Budoff, PhD, MS, samuel.budoff@CUANSCHUTZ.EDU

    Recruiting

Other trials in United States

About this study

Official title: A Double-Blinded, Placebo-Controlled, Randomized, Phase 1/2a Clinical Study to Test the Safety and Efficacy of a Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound

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.

Read more

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.

Being tested
Clemastine Fumarate Combined With Engineered Sound, Clemastine Fumarate Combined With Pink Noise, Placebo Drug With Engineered Sound, Placebo - Placebo
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
Medical subject headings
Language Development Disorders, Hearing Loss, Hearing Disorders, Hearing Loss, Sensorineural, Auditory Diseases, Central, Hearing Loss, Noise-Induced, Hearing Loss, Hidden, Presbycusis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Clemastine Fumarate Combined With Engineered SoundCombination product

    Also called Localized Oligodendrocyte Optimization Therapy, LOOT

    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 NoiseDrug

    Also called Dayhist, Tavist

    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 SoundCombination 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 - PlaceboCombination 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.

Study groups in NCT07304024
Study groupRoleWhat they receive
Treatment GroupExperimentalActive clemastine fumarate + engineered sound stimulation
Receives: Combination Product: Clemastine Fumarate Combined With Engineered Sound
Placebo SoundActive comparatorActive clemastine fumarate + placebo sound (white/pink noise)
Receives: Drug: Clemastine Fumarate Combined With Pink Noise
Placebo DrugPlacebo comparatorPlacebo drug + engineered sound stimulation
Receives: Combination Product: Placebo Drug With Engineered Sound
Control Group - Double PlaceboPlacebo comparatorPlacebo drug + placebo sound (white/pink noise)
Receives: Combination Product: Placebo - Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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.

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

Secondary outcomes (3)

  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.

    Measured: 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.

    Measured: 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Dec 2025
  2. Study start31 Mar 2025
  3. Primary completionJul 2028 (estimated)
  4. Study completionJul 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
344 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07304024
Sponsor's protocol ID
25-1184
Acronym
CAPD-LOOT
Status last verified
Apr 2026
First submitted
19 Dec 2025
Last updated
30 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: IPD will not be shared due to: (1) proprietary nature of the engineered acoustic intervention which is core intellectual property, (2) potentially small sample size due to potential early stopping creates re-identification risks despite de-identification efforts, and (3) lack of dedicated data sharing infrastructure as an academic investigator led trial. Aggregate results will be published in peer-reviewed journals.

Publications

  • 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.

    PubMed 29029896

  • 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.

    PubMed 24997607

  • 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.

    PubMed 34753035

  • 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.

    PubMed 8930778

  • 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.

    PubMed 3678650

  • 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.

    PubMed 15035561

  • 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.

    PubMed 15532670

  • 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.

    PubMed 15817019

  • 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.

    PubMed 8630207

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Clemastine Fumarate Combined With Engineered Sound and Clemastine Fumarate Combined With Pink Noise in people with Central Auditory Processing Disorder and Hearing Impaired (Partially), run by University of Colorado, Denver at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ajay Keerthy, BS (248-421-5796, ajay.keerthy@cuanschutz.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Improvement in hearing-in-noise at 15 degree separation (time frame: At enrollment and again after intervention (Week 5 or 6)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07304024, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2026.

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