RLDP: Efficacy and Safety of Liuwei Dihuang Pill Versus Placebo in Presbycusis With Shen (Kidney)-Yin Deficiency
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LDP group Liuwei Dihuang Pill (LDP）marketed product in China donated by pharmaceutical company. |
Drug: Liuwei Dihuang Pill (marketed product in China)
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.
Other Names:
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| Placebo Comparator: placebo group Same smell, color and shape as Liuwei Dihuang Pill (LDP）without herbs in capsules. |
Drug: Liuwei Dihuang Pill（placebo ）
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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Change in PB-Max after 48 weeks of treatment [48 weeks]
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.
Secondary Outcome Measures
- Change in Speech recognition threshold (SRT) after 24 weeks and 48 weeks of treatment [24 weeks，48 weeks]
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.
- Change in Pure Tone Average (PTA) after 24 weeks and 48 weeks of treatment [24 weeks，48 weeks]
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.
- Change in Shen (Kidney)-Yin Deficiency Syndrome Questionnaire after 12 weeks，24 weeks，36 weeks and 48 weeks of treatment [12 weeks，24 weeks，36 weeks，48 weeks]
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]).
- Change in Tinnitus Handicap Inventory（THI）after 12 weeks，24 weeks，36 weeks and 48 weeks of treatment [12 weeks，24 weeks，36 weeks，48 weeks]
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]).
- Change in Mini-mental State Examination (MMSE) after 12 weeks，24 weeks，36 weeks and 48 weeks of treatment [12 weeks，24 weeks，36 weeks，48 weeks]
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]).
Other Outcome Measures
- Change in ABR after 48 weeks of treatment [48 weeks]
The absolute values of changes in the levels of auditory brainstem response（ABR ）from baseline (week 1 to week 48) between LDP and placebo.
- Change in DPOAE pass rate after 48 weeks of treatment [48 weeks]
The absolute values of changes in the pass rate levels of distortion product otoacoustic emissions（DPOAE）from baseline (week 1 to week 48) between LDP and placebo.
- Change in serum CRP after 48 weeks of treatment [48 weeks]
The absolute values of changes in the levels of serum C-reactive protein (CRP) related to the mechanism from baseline (week 1 to week 48) between LDP and placebo.
- Change in serum IL6 after 48 weeks of treatment [48 weeks]
The absolute values of changes in the levels of serum interleukin 6 (IL-6) related to the mechanism from baseline (week 1 to week 48) between LDP and placebo.
- Change in serum TNF-α after 48 weeks of treatment [48 weeks]
The absolute values of changes in the levels of serum Tumor necrosis factor (TNF-α) related to the mechanism from baseline (week 1 to week 48) between LDP and placebo.
- Change in serum MDA after 48 weeks of treatment [48 weeks]
The absolute values of changes in the levels of serum Malondialdehyde (MDA) related to the mechanism from baseline (week 1 to week 48) between LDP and placebo.
- Change in serum MPO after 48 weeks of treatment [48 weeks]
The absolute values of changes in the levels of serum Myeloperoxidase (MPO) related to the mechanism from baseline (week 1 to week 48) between LDP and placebo.
- Change in serum GSH after 48 weeks of treatment [48 weeks]
The absolute values of changes in the levels of serum L-Glutathione(GSH) related to the mechanism from baseline (week 1 to week 48) between LDP and placebo.
- Change in serum T-AOC after 48 weeks of treatment [48 weeks]
The absolute values of changes in the levels of serum Total antioxidant capacity（T-AOC）related to the mechanism from baseline (week 1 to week 48) between LDP and placebo.
- Change in serum NfL after 48 weeks of treatment [48 weeks]
The absolute values of changes in the levels of serum Neurofilament Light（NfL）related to the mechanism from baseline (week 1 to week 48) between LDP and placebo.
- Change in hemodynamic signals of resting fMRI after 48 weeks of treatment [48 weeks]
The changes in hemodynamic signals of resting functional magnetic resonance imaging (fMRI) related to the mechanism from baseline (week 1 to week 48) between LDP and placebo. 40 patients were selected for this study.
- Adverse Events [24 weeks，48 weeks]
Incidence of adverse events.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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).
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Adult aged 65-75 years inclusive.
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Maximum speech recognition rate in quiet environment is equal to or over 60% with ability to communicate well.
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Subjects have no cognitive impairment with CDR score =0.
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Subjects must have a current diagnosis of Shen (Kidney)-Yin Deficiency.
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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:
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Subjects with sudden hearing loss or pure tone hearing fluctuation within the three months.
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Subjects with a history of serious mental illness.
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Subjects with severe cardiac insufficiency, malignant tumor or other serious systemic diseases.
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Subjects with conductive deafness, congenital deafness, hereditary deafness, inner ear immune and autoimmune inner ear diseases, auditory neuropathy, toxic deafness and noise deafness.
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Subjects with organic ear diseases, abnormal ear structure and symptomatic cerebral infarction.
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Subjects with dementia, neurosyphilis, hypothyroidism and depression.
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Subjects has previously participated in other clinical trial within the three months.
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Subjects with using hearing aids or devices.
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Other situations where the researcher thinks it is inappropriate to participate in this research.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Community Health Service Center of North Sichuan Road, Hongkou District, Shanghai | Shanghai | Shanghai | China | 200081 |
| 2 | Jiaxing Street Community Health Service Center, Hongkou District, Shanghai | Shanghai | Shanghai | China | 200086 |
| 3 | Community Health Service Center of Tianlin Street, Xuhui District, Shanghai | Shanghai | Shanghai | China | 200233 |
| 4 | Sixth people's Hospital Affiliated to Shanghai Jiaotong University | Shanghai | Shanghai | China | 200233 |
| 5 | Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine | Shanghai | Shanghai | China | 200437 |
| 6 | Juquan New Town Community Health Service Center, Gucun Town, Baoshan District, Shanghai | Shanghai | Shanghai | China | 201907 |
Sponsors and Collaborators
- Shanghai Jiao Tong University School of Medicine
- Shanghai University of Traditional Chinese Medicine
Investigators
- Study Director: Jianrong Shi, Doctor, Shanghai Jiao Tong University School of Medicine
- Principal Investigator: Jianning Zhang, Doctor, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine
- Principal Investigator: Ping Huang, Doctor, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine
- Principal Investigator: Hongsheng Tan, Doctor, Shanghai Jiao Tong University School of Medicine
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Bednar MM, DeMartinis N, Banerjee A, Bowditch S, Gaudreault F, Zumpano L, Lin FR. The Safety and Efficacy of PF-04958242 in Age-Related Sensorineural Hearing Loss: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2015 Jul;141(7):607-13. doi: 10.1001/jamaoto.2015.0791.
- Ge JR, Xie LH, Chen J, Li SQ, Xu HJ, Lai YL, Qiu LL, Ni CB. Liuwei Dihuang Pill () Treats Postmenopausal Osteoporosis with Shen (Kidney) Yin Deficiency via Janus Kinase/Signal Transducer and Activator of Transcription Signal Pathway by Up-regulating Cardiotrophin-Like Cytokine Factor 1 Expression. Chin J Integr Med. 2018 Jun;24(6):415-422. doi: 10.1007/s11655-016-2744-2. Epub 2016 Dec 27.
- McLean WJ, Hinton AS, Herby JTJ, Salt AN, Hartsock JJ, Wilson S, Lucchino DL, Lenarz T, Warnecke A, Prenzler N, Schmitt H, King S, Jackson LE, Rosenbloom J, Atiee G, Bear M, Runge CL, Gifford RH, Rauch SD, Lee DJ, Langer R, Karp JM, Loose C, LeBel C. Improved Speech Intelligibility in Subjects With Stable Sensorineural Hearing Loss Following Intratympanic Dosing of FX-322 in a Phase 1b Study. Otol Neurotol. 2021 Aug 1;42(7):e849-e857. doi: 10.1097/MAO.0000000000003120.
- RLDP-2021