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

February 3, 2014 updated by: US Department of Veterans Affairs

Prevention of Cisplatin Ototoxicity With the Antioxidant Alpha-Lipoic Acid

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

39

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
      • Portland, Oregon, United States, 97201
        • VA Medical Center, Portland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
Time Frame: 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.
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
Time Frame: 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.
cisplatin treatment period between 10 weeks and up to 16 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

US Department of Veterans Affairs

Collaborators

Oregon Health and Science University

Investigators

  • Principal Investigator: Dawn L Martin, Portland VA Medical Center, Portland, OR

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

May 23, 2007

First Submitted That Met QC Criteria

May 23, 2007

First Posted (Estimate)

May 24, 2007

Study Record Updates

Last Update Posted (Estimate)

March 7, 2014

Last Update Submitted That Met QC Criteria

February 3, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C4697-R
  • CDR0000546570 (Other Grant/Funding Number: VA RR&D)
  • NCRAR-VA-1810 (Other Grant/Funding Number: VA RR&D)
  • OHSU-3288 (Other Grant/Funding Number: VA RR&D)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Ototoxicity

Clinical Trials on alpha-lipoic acid

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Uruguay

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe