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

Ototoxicity Clinical Trial

Official title:

Prevention of Cisplatin Ototoxicity With the Antioxidant Alpha-Lipoic Acid

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00477607
• Other study ID #: C4697-R
• Secondary ID: CDR0000546570NCR
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: May 23, 2007
• Last updated: February 3, 2014
• Start date: October 2007
• Est. completion date: June 2011

Study information

• Verified date: February 2014
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00570596

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: June 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Ototoxicity
• Unspecified Adult Solid Tumor

Intervention

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.

Behavioral:
• Audiology
otoscopy, immittance screening, noise exposure questionnaire and individualized behavioral pure-tone in the convention and high-frequency ranges.

Biological:
• laboratory biomarker analysis
Plasma concentrations of Malondialdehyde (MDA) will be measures as an indicator of oxidative stress.

Drug:
• Placebo
Placebo will be administered to each patient prior to first cisplatin treatment and continue until 3 months after last treatment.

Locations

Country	Name	City	State
United States	Oregon Health & Science University	Portland	Oregon
United States	VA Medical Center, Portland	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ototoxicity Measurement	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.	No
Secondary	Malondialdehyde (MDA) Levels	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.	No
Secondary	Total Amount of Prescribed Cisplatin Dose Administered	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.	No