A Phase 1/2 interventional study of Clemastine Fumarate Combined With Engineered Sound and Clemastine Fumarate Combined With Pink Noise in Central Auditory Processing Disorder, Hearing Impaired (Partially) and Hearing, sponsored by University of Colorado, Denver. Recruiting at 1 site in United States. Open to participants aged 45 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-04-30.
Sponsored by University of Colorado, Denver · Phase 1/2, Interventional, and Treatment
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.
121 studies on the registry are indexed under Language Development Disorders; 49 are open to participants now.
This study's planned enrollment of 344 is above the median of 74 across 106 interventional studies indexed under Language Development Disorders.
Browse Language Development Disorders studies →University of Colorado, Denver is the lead sponsor of 1,543 studies on the registry; 317 are open to participants now.
Of its 147 completed or terminated interventional studies of FDA-regulated products, 92 (63%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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:
Exclusion Criteria:
Any of the following conditions which are listed as or warnings for use of the clinical trial drug (from labeling):
Taking medications that would contraindicate taking the clinical trial drug; Specifically, (from labeling):
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Active clemastine fumarate + engineered sound stimulation
Combination Product: Clemastine Fumarate Combined With Engineered Sound
Active clemastine fumarate + placebo sound (white/pink noise)
Drug: Clemastine Fumarate Combined With Pink Noise
Placebo drug + engineered sound stimulation
Combination Product: Placebo Drug With Engineered Sound
Placebo drug + placebo sound (white/pink noise)
Combination Product: Placebo - Placebo
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
Drug page: Clemastine
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 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 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.
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)
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)
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)
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)
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)
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)
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)
Plan to share: 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.
Started Mar 2025 (actual). Primary completion is estimated for Jul 2028, 40 months after the start.
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