OtotoxicityPhase 2/3NCT00477607
Alpha-Lipoic Acid in Preventing Hearing Loss in Cancer Patients Undergoing Treatment With Cisplatin
A Phase 2/3 study testing alpha-lipoic acid, Audiology and laboratory biomarker analysis in people with Ototoxicity and Unspecified Adult Solid Tumor, run by US Department of Veterans Affairs at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ototoxicity, Unspecified Adult Solid Tumor
- What is being tested?
- alpha-lipoic acid, Audiology and laboratory biomarker analysis
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2007to Jun 2011
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
VA Medical Center, Portland
Portland, Oregon, 97201
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Official title: 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.
Read the 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.
- Conditions
- Ototoxicity, Unspecified Adult Solid Tumor
- Being tested
- alpha-lipoic acid, Audiology, laboratory biomarker analysis, Placebo
- Medical subject headings
- Ototoxicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
alpha-lipoic acidDrug
Also called 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.
AudiologyBehavioural
Also called ototoxicity monitoring
otoscopy, immittance screening, noise exposure questionnaire and individualized behavioral pure-tone in the convention and high-frequency ranges.
laboratory biomarker analysisBiological
Also called MDA
Plasma concentrations of Malondialdehyde (MDA) will be measures as an indicator of oxidative stress.
PlaceboDrug
Placebo will be administered to each patient prior to first cisplatin treatment and continue until 3 months after last treatment.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Receiving alpha-lipoic acid during cisplatin treatment. Receives: Drug: alpha-lipoic acid; Behavioral: Audiology; Biological: laboratory biomarker analysis |
| Arm 2 | Placebo comparator | Receiving placebo during cisplatin treatment Receives: Behavioral: Audiology; Biological: laboratory biomarker analysis; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline measurement occurred prior to first cisplatin treatment session. Follow-up measurements occurred up to 3 months after last cisplatin treatment.
Secondary outcomes (2)
Malondialdehyde (MDA) Levels
Computed maximum increase relative to baseline for each subject = (max MDA during treatment) - baseline MDA level.
Measured: 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
Maximum cumulative dose of cisplatin (mg/m^2) administered during the course of chemotherapy.
Measured: cisplatin treatment period between 10 weeks and up to 16 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2007 (estimated)
- Study startOct 2007
- Primary completionMar 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for OtotoxicityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- US Department of Veterans Affairs
- Sponsor type
- US federal agency
- Collaborators
- Oregon Health and Science University
- Responsible party
- Sponsor
- Investigators
- Dawn L Martin, Principal investigator, Portland VA Medical Center, Portland, OR
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00477607
- Sponsor's protocol ID
- C4697-R
- Other IDs
- CDR0000546570, NCRAR-VA-1810, OHSU-3288
- Status last verified
- Feb 2014
- First submitted
- 23 May 2007
- Last updated
- 7 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Cisplatin Ototoxicity With the Antioxidant Alpha-Lipoic Acid
- ClinicalTrials.gov ID
- NCT00477607
- Acronym / sponsor ID
- C4697-R
- Conditions
- Ototoxicity, Unspecified Adult Solid Tumor
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- US Department of Veterans AffairsUS federal agency
- Collaborators
- Oregon Health and Science University
- Study start
- Oct 2007
- Primary completion
- Mar 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 24 May 2007 (estimated)
- Results
- Posted 29 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: alpha-lipoic acid, Behavioral: Audiology, Biological: laboratory biomarker analysisReceiving alpha-lipoic acid during cisplatin treatment. |
| Arm 2 | Placebo comparator | Behavioral: Audiology, Biological: laboratory biomarker analysis, Drug: PlaceboReceiving placebo during cisplatin treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| alpha-lipoic acidAlso: lipoic acidSupplements (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. | Drug | Arm 1 |
| AudiologyAlso: ototoxicity monitoringotoscopy, immittance screening, noise exposure questionnaire and individualized behavioral pure-tone in the convention and high-frequency ranges. | Behavioural | Arm 1, Arm 2 |
| laboratory biomarker analysisAlso: MDAPlasma concentrations of Malondialdehyde (MDA) will be measures as an indicator of oxidative stress. | Biological | Arm 1, Arm 2 |
| PlaceboPlacebo will be administered to each patient prior to first cisplatin treatment and continue until 3 months after last treatment. | Drug | Arm 2 |
Primary outcome
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.
2 secondary outcomes
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.
Total Amount of Prescribed Cisplatin Dose Administered
Time frame: cisplatin treatment period between 10 weeks and up to 16 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Ototoxicity
Active, not recruiting
Comparative Study of the Quality of Life of Patients Suffering From OTOTOXICITY Due to Chemotherapy Based on Platinum Salts Fitted With a Hearing Aid Compared to Those Not Fitted.
Cancer, Ototoxicity, Drug-Induced
RecruitingObservational study
Cisplatin-induced Cochlear and Vestibular Damage in Head and Neck Cancer
Ototoxic Hearing Loss, Ototoxicity, Drug-Induced
RecruitingPhase 2
Prevention of Ototoxicity in NTM Patients Treated With IV Amikacin
Ototoxicity, Drug-Induced
Not yet recruitingObservational study
OCCUPATIONAL NOISE AND CHEMICAL EXPOSURE EFFECTS ON AUDITORY AND VESTIBULAR FUNCTION
Occupational Noise Exposure
RecruitingPhase 3
A Study of Treatment for Medulloblastoma Using Sodium Thiosulfate to Reduce Hearing Loss
Childhood Medulloblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dawn L Martin principal investigator
Portland VA Medical Center, Portland, OR
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing alpha-lipoic acid, Audiology and laboratory biomarker analysis in people with Ototoxicity and Unspecified Adult Solid Tumor, run by US Department of Veterans Affairs at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2014.