Efficacy and Safety of Liuwei Dihuang Pill Versus Placebo in Presbycusis With Shen (Kidney)-Yin Deficiency

Study Overview
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Brief Summary
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The objective of this study is to examine the effects and safety of Liuwei Dihuang pill and placebo in presbycusis with Shen (kidney)-yin deficiency.

Detailed Description
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There are no approved pharmacologic therapies for age-related hearing loss (ARHL), also known as presbycusis. Based on the syndrome differentiation in Chinese medicine (CM) theory, the pathogenesis of presbycusis is related to the Shen (kidney)-yin deficiency. Liuwei Dihuang Pill (LDP) is effective and commonly prescribed for the treatment of Shen-yin deficiency. The main purpose of this study is to try to demonstrate an improvement in phonetically balanced maximum (PBmax) after 1 years of treatment with the LDP versus the placebo. Subjects will undergo a safety follow-up after the treatment period. Safety and efficacy will be determined by looking at a number of assessments (physical examinations, blood sampling, hearing assessments, questionnaires, etc.).The amount of drug in the blood will also be measured. It is expected that around 120 people (at least 60 in each arm) with presbycusis with Shen (kidney)-yin deficiency may take part in the study. The study participants will be recruited at around 6 sites in the Shanghai, China.

Official Title
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RCT Study of Liuwei Dihuang Pill Preventing and Treating Presbycusis With Shen (Kidney)-Yin Deficiency

Conditions
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Presbycusis, Age-related Hearing Loss, Hearing Disorders and Deafness

Intervention / Treatment
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* Drug: Liuwei Dihuang Pill (marketed product in China)
* Drug: Liuwei Dihuang Pill（placebo ）


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have a current diagnosis of presbyacusis with symmetrical hearing loss, defined as 15-dB or less difference in pure tone average between ears at 0.5, 1, 2 and 4kHz. The average hearing threshold loss level is mild or moderate (20 ≤ average hearing threshold < 50 dBHL). Adult aged 65-75 years inclusive. Maximum speech recognition rate in quiet environment is equal to or over 60% with ability to communicate well. Subjects have no cognitive impairment with CDR score =0. Subjects must have a current diagnosis of Shen (Kidney)-Yin Deficiency. Subjects have read and voluntarily signed the Informed Consent Form (ICF) after all questions have been answered and prior to any study-mandated procedure. Exclusion Criteria: Subjects with sudden hearing loss or pure tone hearing fluctuation within the three months. Subjects with a history of serious mental illness. Subjects with severe cardiac insufficiency, malignant tumor or other serious systemic diseases. Subjects with conductive deafness, congenital deafness, hereditary deafness, inner ear immune and autoimmune inner ear diseases, auditory neuropathy, toxic deafness and noise deafness. Subjects with organic ear diseases, abnormal ear structure and symptomatic cerebral infarction. Subjects with dementia, neurosyphilis, hypothyroidism and depression. Subjects has previously participated in other clinical trial within the three months. Subjects with using hearing aids or devices. Other situations where the researcher thinks it is inappropriate to participate in this research.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Phase 2 Randomized, Double-blind, Placebo-controlled, Multicenter Study of Liuwei Dihuang Pill Administered by taking orally in Adults With Presbycusis With Shen (Kidney)-Yin Deficiency.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDP group<br>Liuwei Dihuang Pill (LDP）marketed product in China donated by pharmaceutical company. | Drug: Liuwei Dihuang Pill (marketed product in China)<br>* LDP group and placebo group were used for treatment. The random number is generated by the central randomization system. All the recruiters were divided into placebo group and LDP group. The numbers will be assigned according to random numbers. In this study, qualified subjects were randomly assigned to the LDP group and placebo group at a ratio of 1:1. The drug was administered for 48 weeks, 3 times a day, 8 pills each time.<br>* Other names: Liu Wei Di Huang Pill;|
| Placebo Comparator: placebo group<br>Same smell, color and shape as Liuwei Dihuang Pill (LDP）without herbs in capsules. | Drug: Liuwei Dihuang Pill（placebo ）<br>* LDP group and placebo group were used for treatment. The random number is generated by the central randomization system. All the recruiters were divided into placebo group and LDP group. The numbers will be assigned according to random numbers. In this study, qualified subjects were randomly assigned to the LDP group and placebo group at a ratio of 1:1. The drug was administered for 48 weeks, 3 times a day, 8 pills each time.<br>* Other names: placebo group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PB-Max after 48 weeks of treatment | To compare the change in PB-Max using the Word Recognition in Quiet test measured with Consonant-Nucleus-Consonant (CNC) word lists from baseline (week 1 to week 48) between LDP and placebo. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Speech recognition threshold (SRT) after 24 weeks and 48 weeks of treatment | To compare the change in Speech recognition threshold (SRT) using the Word Recognition in Quiet test measured with Consonant-Nucleus-Consonant (CNC) word lists from baseline (week 1 to week 24，week 48) between LDP and placebo. | 24 weeks，48 weeks | 
| Change in Pure Tone Average (PTA) after 24 weeks and 48 weeks of treatment | To compare the change in Pure Tone Average (PTA) using the Air conduction audiometry for hearing at certain range (Hz) from baseline (week 1 to week 24，week 48) between LDP and placebo. | 24 weeks，48 weeks | 
| Change in Shen (Kidney)-Yin Deficiency Syndrome Questionnaire after 12 weeks，24 weeks，36 weeks and 48 weeks of treatment | To compare the change in Shen (Kidney)-Yin Deficiency Syndrome Questionnaire using Face to face Interview for the scores from baseline (week 1 to week 12，week 24，week 36 and week 48) between LDP and placebo (range, 0 [best] to 100 [worst]). | 12 weeks，24 weeks，36 weeks，48 weeks | 
| Change in Tinnitus Handicap Inventory（THI）after 12 weeks，24 weeks，36 weeks and 48 weeks of treatment | To compare the change in Tinnitus Handicap Inventory（THI）using Face to face Interview for the scores from baseline (week 1 to week 12，week 24，week 36 and week 48) between LDP and placebo (range, 0 [best] to 100 [worst]). | 12 weeks，24 weeks，36 weeks，48 weeks | 
| Change in Mini-mental State Examination (MMSE) after 12 weeks，24 weeks，36 weeks and 48 weeks of treatment | To compare the change in Mini-mental State Examination (MMSE) using Face to face Interview for the scores from baseline (week 1 to week 12，week 24，week 36 and week 48) between LDP and placebo (range, 0 [worst] to 100 [best]). | 12 weeks，24 weeks，36 weeks，48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Presbycusis, Age-related hearing loss, Liuwei Dihuang Pill