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

This study has been completed.
Sponsor:
Collaborator:
Oregon Health and Science University
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00477607
First received: May 23, 2007
Last updated: February 3, 2014
Last verified: February 2014

May 23, 2007
February 3, 2014
October 2007
March 2011   (final data collection date for primary outcome measure)
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. ] [ Designated as safety issue: No ]

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.
  • Ototoxicity measurement
  • Malondialdehyde levels
  • Serum α-lipoic acid levels
Complete list of historical versions of study NCT00477607 on ClinicalTrials.gov Archive Site
  • 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. ] [ Designated as safety issue: No ]
    Computed maximum increase relative to baseline for each subject = (max MDA during treatment) - baseline MDA level.
  • Total Amount of Prescribed Cisplatin Dose Administered [ Time Frame: cisplatin treatment period between 10 weeks and up to 16 weeks. ] [ Designated as safety issue: No ]
    Maximum cumulative dose of cisplatin (mg/m^2) administered during the course of chemotherapy.
  • Tumor progression
  • Toxicity
  • Response
Not Provided
Not Provided
 
Alpha-Lipoic Acid in Preventing Hearing Loss in Cancer Patients Undergoing Treatment With Cisplatin
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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
  • Ototoxicity
  • Unspecified Adult Solid Tumor
  • 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 Name: lipoic acid
  • Behavioral: Audiology
    otoscopy, immittance screening, noise exposure questionnaire and individualized behavioral pure-tone in the convention and high-frequency ranges.
    Other Name: ototoxicity monitoring
  • Biological: laboratory biomarker analysis
    Plasma concentrations of Malondialdehyde (MDA) will be measures as an indicator of oxidative stress.
    Other Name: MDA
  • Drug: Placebo
    Placebo will be administered to each patient prior to first cisplatin treatment and continue until 3 months after last treatment.
  • Experimental: Arm 1
    Receiving alpha-lipoic acid during cisplatin treatment.
    Interventions:
    • Drug: alpha-lipoic acid
    • Behavioral: Audiology
    • Biological: laboratory biomarker analysis
  • Placebo Comparator: Arm 2
    Receiving placebo during cisplatin treatment
    Interventions:
    • Behavioral: Audiology
    • Biological: laboratory biomarker analysis
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
39
June 2011
March 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00477607
C4697-R, CDR0000546570, NCRAR-VA-1810, OHSU-3288
Yes
Department of Veterans Affairs
Department of Veterans Affairs
Oregon Health and Science University
Principal Investigator: Dawn L Martin Portland VA Medical Center, Portland, OR
Department of Veterans Affairs
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP