Effects of Huperzine A on Presbycusis(Δ,kHz, dB,MMSE, AD)

Study Overview
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Brief Summary
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To investigate the effects of huperzine A on tinnitus suppression, hearing and cognitive function protection in patients with presbycusis-related subjective tinnitus and cognitive impairment.

Detailed Description
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This study is a randomized, controlled trial. 60 eligible participants in total will be recruited. Participants in each group will be evenly and randomly assigned to the huperzine A subgroup and control subgroup using simple randomization method. Participants in the treatment subgroup will receive huperzine A (a dose of 0.2 mg/time, 2 times/day) with basic treatment and health education(BTHE), and those in the control subgroup will receive BTHE only. The primary outcome (auditory function) and secondary outcomes (tinnitus, cognitive symptom and quality of life) will be evaluated at baseline, 3-, 6-, 12-month follow-up.

Official Title
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Effects of Huperzine A on Presbycusis-related Subjective Tinnitus and Cognitive Impairment

Conditions
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Presbycusis, Tinnitus, Cognitive Impairment

Intervention / Treatment
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* Drug: BTHE and Huperzine A
* Other: BETH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) 60 to 85 years old; (2) Mild-to-moderate sensorineural hearing loss (the pure tone averaged across octave frequencies between 0.25 to 4kHz of 26-70 dB HL), with subjective tinnitus, subjective cognitive decline or mild cognitive impairment; (3) Able to tolerate huperzine A treatment; (4) more than 3 months' experience of constant tinnitus; (5) Tinnitus Handicap Inventory score values >10; (6) No participation in any other clinical trial in the past 3 months; (7) Able to accomplish relevant tests and follow-up. Exclusion Criteria: (1) Conductive hearing loss; (2) current (3+ months) hearing aid(s) user; (3) Dependence due to poor physical activity; (4) Allergic to huperzine A; (5) History of malignancy within 5 years or other serious medical conditions before screening, including severe bradycardia, hypotension, angina, asthma, ileus, renal insufficiency, neurological diseases (e.g. epilepsy), psychiatric disorder (e.g. schizophrenia, severe depression and anxiety); (6) Acute brain trauma and stroke within 2 weeks; (7) history of general pain disorder and the use of pain relief drugs on a regular basis; (8) Patients who have started treatment or made changes in treatment with drugs known to influence tinnitus within 6 weeks before investigation starts. (9) Individuals simultaneously or previously (within 30 days prior to investigation start) participate in a clinical investigation using experimental drugs or devices. (10) Ongoing serious life event; (11) Vision impairment.

Ages Eligible for Study
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Minimum Age: 60 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: The studies were divided into 2 groups: Control subgroup and huperzine A group.The study is a single-center, randomized, basic treatment and health education controlled trial, with minimized allocation of patients to one of the two groups. For the study of tinnitus intervention, there is a 3 to 12 month follow-up.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Huperzine A intervention<br>Huperzine A intervention: Huperzine A with a dose 0.1 0.2 mg/time, 2 times/day. BTHE：basic treatment and health education | Drug: BTHE and Huperzine A<br>* huperzine A intervention<br>* Other names: acetylcholinesterase inhibitor;Other: BETH<br>* basic treatment and health education<br>|
| Sham Comparator: control<br>Participants in the BTHE group will receive advice regarding lifestyle modification, avoiding alcohol and cigarette consumption. | Drug: BTHE and Huperzine A<br>* huperzine A intervention<br>* Other names: acetylcholinesterase inhibitor;Other: BETH<br>* basic treatment and health education<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hearing function protection | All participants (including with tinnitus and without tinnitus) will report in the measure. Δ value of averaged hearing threshold = re-test threshold - initial threshold, Δ value of averaged hearing threshold ≤ 0 showed good responders, and > 0 showed poor responders. | 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| global cognitive function protection | All participants (including with tinnitus and without tinnitus) will report in the outcome measure. ΔMMSE = re-test MMSE - initial MMSE, ΔMMSE< 0 showed poor responders and hearing threshold ≤ 0 showed good responders; and > 0 showed poor responders ΔMMSE≥ 0 showed good responders | 1 years | 
| special cognitive domains:orientation to time, orientation to place, registration, attention and calculations,recall, language,repetition and complex commands | MMSE scale in different domains (MMSE SCALE, 0-30) | 1 years | 
| Tinnitus suppression | 150 participants with tinnitus will report in the outcome measure. Method 1: tinnitus functional index (0 100，≤25，relatively mild tinnitus; 25 50,significant problems with tinnitus; ≥50, tinnitus severe enough ）. method 2:no effect on tinnitus was showed 0; symptomatic alleviation was showed 1;and tinnitus disappear was showed 2 | 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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presbycusis, tinnitus, cognitive impairment, Huperzine A, age-related hearing impairment