Recruiting
Phase 1
Phase 2

Clemastine Fumarate

Sponsor:

University of Colorado, Denver

Code:

NCT07304024

Conditions

Central Auditory Processing Disorder

Hearing Impaired (Partially)

Hearing

Hearing Abnormality

Hearing Disability

Eligibility Criteria

Sex: All

Age: 45 - 65

Healthy Volunteers: Not accepted

Interventions

Clemastine Fumarate Combined With Engineered Sound

Clemastine Fumarate Combined With Pink Noise

Placebo Drug With Engineered Sound

Placebo - Placebo

Study Details

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

Central Auditory Processing Disorder

Hearing Impaired (Partially)

Hearing

Hearing Abnormality

Hearing Disability

Study ID

NCT07304024

Start date

Mar 31, 2025

Status verified date

Apr, 2026

Completion date

Jul, 2028

Anticipated

Primary completion date

Jul, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 45 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • 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.

Study Design

Enrollment

344 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment Group

Active clemastine fumarate + engineered sound stimulation

active comparator: Placebo Sound

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

placebo comparator: Placebo Drug

Placebo drug + engineered sound stimulation

placebo comparator: Control Group - Double Placebo

Placebo drug + placebo sound (white/pink noise)

Interventions

Clemastine Fumarate Combined With Engineered Sound

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 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

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

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.

Primary outcome measure

  • Improvement in hearing-in-noise at 15 degree separation [ Time Frame: At enrollment and again after intervention (Week 5 or 6) ]
  • Improvement in hearing-in-noise at 30 degree separation [ Time Frame: At enrollment and again after intervention (Week 5 or 6) ]

Central Contacts and Locations

Central contacts

Ajay Keerthy, BS

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

Locations

University of Colorado Anschutz Medical Center

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Achim Klug, PhD

303-724-4621achim.klug@cuanschutz.edu

Samuel Budoff, PhD, MS

samuel.budoff@CUANSCHUTZ.EDU

Principal Investigator:

Achim Klug, PhD

More Information

Sponsor

University of Colorado, Denver

Last update posted

Apr 30, 2026

Last verified

Apr, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-15. This information was provided to ClinicalTrials.gov by University of Colorado, Denver on 2026-04-30.