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
  Purpose

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.


Condition Intervention Phase
Ototoxicity
Unspecified Adult Solid Tumor
Drug: alpha-lipoic acid
Behavioral: Audiology
Biological: laboratory biomarker analysis
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Prevention of Cisplatin Ototoxicity With the Antioxidant Alpha-Lipoic Acid

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 39
Study Start Date: October 2007
Study Completion Date: June 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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
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 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • No other concurrent antioxidants or vitamin E > 100 IU per day
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00477607

Locations
United States, Oregon
VA Medical Center, Portland
Portland, Oregon, United States, 97201
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Oregon Health and Science University
Investigators
Principal Investigator: Dawn L Martin Portland VA Medical Center, Portland, OR
  More Information

Additional Information:
No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00477607     History of Changes
Obsolete Identifiers: NCT00570596
Other Study ID Numbers: C4697-R, CDR0000546570, NCRAR-VA-1810, OHSU-3288
Study First Received: May 23, 2007
Results First Received: October 4, 2013
Last Updated: February 3, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Additional relevant MeSH terms:
Cisplatin
Thioctic Acid
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on September 16, 2014