| ID | Type | Description | Link |
|---|---|---|---|
| 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 |
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| Name | Class |
|---|---|
| Oregon Health and Science University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Experimental | Receiving alpha-lipoic acid during cisplatin treatment. |
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| Arm 2 | Placebo Comparator | Receiving placebo during cisplatin treatment |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| alpha-lipoic acid | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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
| Baseline measurement occurred prior to first cisplatin treatment session. Follow-up measurements occurred up to 3 months after last cisplatin treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Total Amount of Prescribed Cisplatin Dose Administered |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dawn L Martin | Portland VA Medical Center, Portland, OR | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Medical Center, Portland | Portland | Oregon | 97201 | United States | ||
| Oregon Health & Science University |
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| ID | Title | Description |
|---|---|---|
| FG000 | Alpha-lipoic Acid | Receiving alpha-lipoic acid during cisplatin treatment. alpha-lipoic acid : Supplements (1200mg once a day) was administered to each patient prior to first cisplatin treatment and continued until 3 months after last treatment. |
| FG001 | Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Audiology | Behavioral | otoscopy, immittance screening, noise exposure questionnaire and individualized behavioral pure-tone in the convention and high-frequency ranges. |
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| laboratory biomarker analysis | Biological | Plasma concentrations of Malondialdehyde (MDA) will be measures as an indicator of oxidative stress. |
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| Placebo | Drug | Placebo will be administered to each patient prior to first cisplatin treatment and continue until 3 months after last treatment. |
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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. |
| Portland |
| Oregon |
| 97239 |
| United States |
Receiving placebo during cisplatin treatment Placebo supplements (1200mg once a day) were administered to each patient prior to first cisplatin treatment and continued until 3 months after last treatment. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1 | Receiving alpha-lipoic acid during cisplatin treatment. laboratory biomarker analysis : Plasma concentrations of Malondialdehyde (MDA) will be measures as an indicator of oxidative stress. 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. Audiology : otoscopy, immittance screening, noise exposure questionnaire and individualized behavioral pure-tone in the convention and high-frequency ranges. |
| BG001 | Arm 2 | Receiving placebo during cisplatin treatment Audiology : otoscopy, immittance screening, noise exposure questionnaire and individualized behavioral pure-tone in the convention and high-frequency ranges. 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. laboratory biomarker analysis : Plasma concentrations of Malondialdehyde (MDA) will be measures as an indicator of oxidative stress. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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
| Intent-to-treat (ITT) | Posted | Number | participants | Baseline measurement occurred prior to first cisplatin treatment session. Follow-up measurements occurred up to 3 months after last cisplatin treatment. |
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| Secondary | Malondialdehyde (MDA) Levels | Computed maximum increase relative to baseline for each subject = (max MDA during treatment) - baseline MDA level. | Non-missing MDA measurements from 23 subjects in primary outcome analysis | Posted | Mean | Standard Deviation | uM=micro-moles/liter | Baseline measurement occurred prior to first cisplatin treatment session. Follow-up measurements occurred up to 3 months after last cisplatin treatment. |
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| Secondary | Total Amount of Prescribed Cisplatin Dose Administered | Maximum cumulative dose of cisplatin (mg/m^2) administered during the course of chemotherapy. | Subjects from the original 39 recruited who had sufficient chemotherapy data recorded to measure cumulative dose. | Posted | Mean | Standard Deviation | mg/m^2 | cisplatin treatment period between 10 weeks and up to 16 weeks. |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1 | Receiving alpha-lipoic acid during cisplatin treatment. laboratory biomarker analysis : Plasma concentrations of Malondialdehyde (MDA) will be measures as an indicator of oxidative stress. 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. Audiology : otoscopy, immittance screening, noise exposure questionnaire and individualized behavioral pure-tone in the convention and high-frequency ranges. | 5 | 19 | 3 | 19 | ||
| EG001 | Arm 2 | Receiving placebo during cisplatin treatment Audiology : otoscopy, immittance screening, noise exposure questionnaire and individualized behavioral pure-tone in the convention and high-frequency ranges. 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. laboratory biomarker analysis : Plasma concentrations of Malondialdehyde (MDA) will be measures as an indicator of oxidative stress. | 6 | 20 | 2 | 20 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Nausea/vomitting | Gastrointestinal disorders | Systematic Assessment |
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| Blood transfusion | Blood and lymphatic system disorders | Systematic Assessment |
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| Acute Renal Failure | Renal and urinary disorders | Systematic Assessment |
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| Pancreatitis | Endocrine disorders | Systematic Assessment |
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| Esophagitis | Gastrointestinal disorders | Systematic Assessment |
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| sceptic shock | Infections and infestations | Systematic Assessment |
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| hypoxic respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Small bowel obstruction | Gastrointestinal disorders | Systematic Assessment |
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| Spine pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Distended abdomen | Gastrointestinal disorders | Systematic Assessment |
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| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
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| Muscle Weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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Missing data constraints have the number of subjects in the study being different for different outcomes.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dawn Konrad-Martin | VA RR&D National Center for Rehbilitative Auditory Research | 503-220-8262 | 52962 | dawn.martin@va.gov |
| ID | Term |
|---|---|
| D000081015 | Ototoxicity |
| ID | Term |
|---|---|
| D004427 | Ear Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011832 | Radiation Injuries |
| D014947 | Wounds and Injuries |
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| ID | Term |
|---|---|
| D008063 | Thioctic Acid |
| ID | Term |
|---|---|
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D005227 | Fatty Acids |
| D008055 | Lipids |
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| >=65 years |
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| Male |
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