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

Phase 2

Completed

• Conditions: Ototoxicity; Unspecified Adult Solid Tumor
• Interventions: Drug: alpha-lipoic acid; Behavioral: Audiology; Biological: laboratory biomarker analysis; Drug: Placebo

• Registration Number: NCT00477607
• Lead Sponsor: US Department of Veterans Affairs

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.

Study Timeline

• Study First Submitted: 2007-05-23
• Study First Submitted QC: 2007-05-23
• Study First Posted: 2007-05-24
• Study Start: 2007-10
• Primary Completion: 2011-03
• Study Completion: 2011-06
• Results First Submitted: 2013-10-04
• Results First Submitted QC: 2013-12-10
• Results First Posted: 2014-01-29
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-03
• Last Update Posted: 2014-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	Audiology	Receiving alpha-lipoic acid during cisplatin treatment.
Arm 1	laboratory biomarker analysis	Receiving alpha-lipoic acid during cisplatin treatment.
Arm 2	Audiology	Receiving placebo during cisplatin treatment
Arm 2	laboratory biomarker analysis	Receiving placebo during cisplatin treatment
Arm 2	Placebo	Receiving placebo during cisplatin treatment
Arm 1	alpha-lipoic acid	Receiving alpha-lipoic acid during cisplatin treatment.

Primary Outcome Measures

Name	Time	Method
Ototoxicity Measurement	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 Outcome Measures

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

Trial Locations

Locations (2)

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

VA Medical Center, Portland; 🇺🇸 Portland, Oregon, United States