Prevention of Cisplatin Ototoxicity With the Antioxidant Alpha-Lipoic Acid
Overview
- Phase
- Phase 2
- Intervention
- alpha-lipoic acid
- Conditions
- Ototoxicity
- Sponsor
- US Department of Veterans Affairs
- Enrollment
- 39
- Locations
- 2
- Primary Endpoint
- Ototoxicity Measurement
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Arm 1
Receiving alpha-lipoic acid during cisplatin treatment.
Intervention: alpha-lipoic acid
Arm 1
Receiving alpha-lipoic acid during cisplatin treatment.
Intervention: Audiology
Arm 1
Receiving alpha-lipoic acid during cisplatin treatment.
Intervention: laboratory biomarker analysis
Arm 2
Receiving placebo during cisplatin treatment
Intervention: Audiology
Arm 2
Receiving placebo during cisplatin treatment
Intervention: laboratory biomarker analysis
Arm 2
Receiving placebo during cisplatin treatment
Intervention: Placebo
Outcomes
Primary Outcomes
Ototoxicity Measurement
Time Frame: Baseline measurement occurred prior to first cisplatin treatment session. Follow-up measurements occurred up to 3 months after last cisplatin treatment.
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.
Secondary Outcomes
- Total Amount of Prescribed Cisplatin Dose Administered(cisplatin treatment period between 10 weeks and up to 16 weeks.)
- Malondialdehyde (MDA) Levels(Baseline measurement occurred prior to first cisplatin treatment session. Follow-up measurements occurred up to 3 months after last cisplatin treatment.)