Clinical trial NCT05125081: Efficacy and Safety of Liuwei Dihuang Pill Versus Placebo in Presbycusis With Shen (Kidney)-Yin Deficiency
Official title: RCT Study of Liuwei Dihuang Pill Preventing and Treating Presbycusis With Shen (Kidney)-Yin Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Presbycusis
Age-related Hearing Loss
Hearing Disorders and Deafness
Keywords: Presbycusis
Age-related hearing loss
Liuwei Dihuang Pill
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Shanghai University of Traditional Chinese Medicine
First posted: 2021-11-18
Enrollment: 120
Sex: ALL
Minimum age (years): 65
Maximum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. 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).
2. Adult aged 65-75 years inclusive.
3. Maximum speech recognition rate in quiet environment is equal to or over 60% with ability to communicate well.
4. Subjects have no cognitive impairment with CDR score =0.
5. Subjects must have a current diagnosis of Shen (Kidney)-Yin Deficiency.
6. 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:

1. Subjects with sudden hearing loss or pure tone hearing fluctuation within the three months.
2. Subjects with a history of serious mental illness.
3. Subjects with severe cardiac insufficiency, malignant tumor or other serious systemic diseases.
4. Subjects with conductive deafness, congenital deafness, hereditary deafness, inner ear immune and autoimmune inner ear diseases, auditory neuropathy, toxic deafness and noise deafness.
5. Subjects with organic ear diseases, abnormal ear structure and symptomatic cerebral infarction.
6. Subjects with dementia, neurosyphilis, hypothyroidism and depression.
7. Subjects has previously participated in other clinical trial within the three months.
8. Subjects with using hearing aids or devices.
9. Other situations where the researcher thinks it is inappropriate to participate in this research.

Primary outcomes:
measure: Change in PB-Max after 48 weeks of treatment
timeFrame: 48 weeks
Secondary outcomes:
measure: Change in Speech recognition threshold (SRT) after 24 weeks and 48 weeks of treatment
timeFrame: 24 weeks，48 weeks
measure: Change in Pure Tone Average (PTA) after 24 weeks and 48 weeks of treatment
timeFrame: 24 weeks，48 weeks
measure: Change in Shen (Kidney)-Yin Deficiency Syndrome Questionnaire after 12 weeks，24 weeks，36 weeks and 48 weeks of treatment
timeFrame: 12 weeks，24 weeks，36 weeks，48 weeks
measure: Change in Tinnitus Handicap Inventory（THI）after 12 weeks，24 weeks，36 weeks and 48 weeks of treatment
timeFrame: 12 weeks，24 weeks，36 weeks，48 weeks
measure: Change in Mini-mental State Examination (MMSE) after 12 weeks，24 weeks，36 weeks and 48 weeks of treatment
timeFrame: 12 weeks，24 weeks，36 weeks，48 weeks
Other outcomes:
measure: Change in ABR after 48 weeks of treatment
timeFrame: 48 weeks
measure: Change in DPOAE pass rate after 48 weeks of treatment
timeFrame: 48 weeks
measure: Change in serum CRP after 48 weeks of treatment
timeFrame: 48 weeks
measure: Change in serum IL6 after 48 weeks of treatment
timeFrame: 48 weeks
measure: Change in serum TNF-α after 48 weeks of treatment
timeFrame: 48 weeks
measure: Change in serum MDA after 48 weeks of treatment
timeFrame: 48 weeks
measure: Change in serum MPO after 48 weeks of treatment
timeFrame: 48 weeks
measure: Change in serum GSH after 48 weeks of treatment
timeFrame: 48 weeks
measure: Change in serum T-AOC after 48 weeks of treatment
timeFrame: 48 weeks
measure: Change in serum NfL after 48 weeks of treatment
timeFrame: 48 weeks
measure: Change in hemodynamic signals of resting fMRI after 48 weeks of treatment
timeFrame: 48 weeks
measure: Adverse Events
timeFrame: 24 weeks，48 weeks
Locations:
city: Shanghai
country: China
facility: Community Health Service Center of North Sichuan Road, Hongkou District, Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Jiaxing Street Community Health Service Center, Hongkou District, Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Community Health Service Center of Tianlin Street, Xuhui District, Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Sixth people's Hospital Affiliated to Shanghai Jiaotong University
state: Shanghai
city: Shanghai
country: China
facility: Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine
state: Shanghai
city: Shanghai
country: China
facility: Juquan New Town Community Health Service Center, Gucun Town, Baoshan District, Shanghai
state: Shanghai
Study officials:
affiliation: Shanghai Jiao Tong University School of Medicine
name: Jianrong Shi, Doctor
role: STUDY_DIRECTOR
affiliation: Yueyang Hospital of Integrated Traditional Chinese and Western Medicine
name: Jianning Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Yueyang Hospital of Integrated Traditional Chinese and Western Medicine
name: Ping Huang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Jiao Tong University School of Medicine
name: Hongsheng Tan, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.