Alpha-Lipoic Acid in Preventing Hearing Loss in Cancer Patients Undergoing Treatment With Cisplatin

Study Overview
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Brief Summary
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RATIONALE: Alpha-lipoic acid may prevent or lessen hearing loss caused by cisplatin. PURPOSE: This randomized clinical trial is studying the effectiveness of alpha-lipoic acid in preventing hearing loss in cancer patients undergoing treatment with cisplatin.

Detailed Description
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OBJECTIVES: Primary Determine the ability of alpha-lipoic acid supplementation to prevent or reduce the incidence and severity of hearing loss in cancer patients undergoing treatment with cisplatin. Secondary Determine if this drug improves the oxidative state, as measured by a malondialdehyde measurement of oxidative stress, thereby protecting the patient against ototoxic-induced hearing loss. OUTLINE: This is a placebo-controlled, double-blind, randomized, multicenter study. Patients are stratified by cancer stage and institution. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral alpha-lipoic acid supplement once a day beginning 1 week before the start of cisplatin treatment and continuing for up to 1 month after the completion of cisplatin. During cisplatin treatment, patients discontinue supplement 1 day prior to the cisplatin treatment and resume daily supplements 2 days post treatment. Arm II: Patients receive oral placebo supplement once a day beginning 1 week before the start of cisplatin and continuing for up to 1 month after the completion of cisplatin. During cisplatin treatment, patients discontinue supplement 1 day prior to the cisplatin treatment and resume daily supplements 2 days post treatment. Hearing and ototoxicity are assessed at baseline, on each day of chemotherapy, and at 1 and 3 months post chemotherapy. Blood samples are collected periodically to measure malondialdehyde and alpha-lipoic acid levels. After completion of treatment with cisplatin, patients are followed for 3 months.

Official Title
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Prevention of Cisplatin Ototoxicity With the Antioxidant Alpha-Lipoic Acid

Conditions
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Ototoxicity, Unspecified Adult Solid Tumor

Intervention / Treatment
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* Drug: alpha-lipoic acid
* Behavioral: Audiology
* Biological: laboratory biomarker analysis
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of cancer Receiving therapeutic treatment with cisplatin Fertile patients must use effective contraception during and for 3 months after completion of study treatment Cognitively and physically able to participate in the study Must be able to provide reliable behavioral threshold responses (patient must meet intra-session reliability criterion of +/- 5 dB) At least 6 months since prior treatment with cisplatin or other ototoxic medications (e.g., aminoglycoside antibiotics) At least 6 months since prior and no concurrent radiotherapy for head and neck tumors Concurrent radiotherapy targeted below the neck allowed More than 1 month since prior alpha-lipoic acid supplements Exclusion Criteria: No aggressive behavior as indicated in electronic chart notes No documented dementia No Alzheimer's disease No severe psychosocial disorder No active or recent history of middle ear disorder based on otoscopy, tympanometry, immittance, or notes in patient chart No renal disease No Meniere's disease or retrocochlear disorder based on patient report or notes in patient's chart Not receiving treatment for diabetes mellitus No concurrent vincristine or vinblastine No other concurrent investigational therapy No other concurrent antioxidants or vitamin E > 100 IU per day

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Receiving alpha-lipoic acid during cisplatin treatment. | Drug: alpha-lipoic acid<br>* Supplements (1200mg once a day) or placebo will be administered to each patient prior to first cisplatin treatment and continue until 3 months after last treatment.<br>* Other names: lipoic acid;Behavioral: Audiology<br>* otoscopy, immittance screening, noise exposure questionnaire and individualized behavioral pure-tone in the convention and high-frequency ranges.<br>* Other names: ototoxicity monitoring;Biological: laboratory biomarker analysis<br>* Plasma concentrations of Malondialdehyde (MDA) will be measures as an indicator of oxidative stress.<br>* Other names: MDA;|
| Placebo Comparator: Arm 2<br>Receiving placebo during cisplatin treatment | Behavioral: Audiology<br>* otoscopy, immittance screening, noise exposure questionnaire and individualized behavioral pure-tone in the convention and high-frequency ranges.<br>* Other names: ototoxicity monitoring;Biological: laboratory biomarker analysis<br>* Plasma concentrations of Malondialdehyde (MDA) will be measures as an indicator of oxidative stress.<br>* Other names: MDA;Drug: Placebo<br>* Placebo will be administered to each patient prior to first cisplatin treatment and continue until 3 months after last treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ototoxicity Measurement | Any American Speech and Hearing Association (ASHA)-significant hearing loss in the Sensitive Region for Ototoxicity frequencies between baseline measurement and any follow-up measurement. ASHA criteria are defined as 20 decibel (dB) increase at any test frequency, 10 dB increase at any two consecutive test frequencies, or loss of response where there was previously a response at any three test frequencies. | Baseline measurement occurred prior to first cisplatin treatment session. Follow-up measurements occurred up to 3 months after last cisplatin treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Malondialdehyde (MDA) Levels | Computed maximum increase relative to baseline for each subject = (max MDA during treatment) - baseline MDA level. | Baseline measurement occurred prior to first cisplatin treatment session. Follow-up measurements occurred up to 3 months after last cisplatin treatment. | 
| Total Amount of Prescribed Cisplatin Dose Administered | Maximum cumulative dose of cisplatin (mg/m^2) administered during the course of chemotherapy. | cisplatin treatment period between 10 weeks and up to 16 weeks. |