Trial Outcomes & Findings for Alpha-Lipoic Acid in Preventing Hearing Loss in Cancer Patients Undergoing Treatment With Cisplatin (NCT NCT00477607)
NCT ID: NCT00477607
Last Updated: 2014-03-07
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
39 participants
Primary outcome timeframe
Baseline measurement occurred prior to first cisplatin treatment session. Follow-up measurements occurred up to 3 months after last cisplatin treatment.
Results posted on
2014-03-07
Participant Flow
Participant milestones
| Measure |
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.
|
Placebo
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.
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
20
|
|
Overall Study
COMPLETED
|
12
|
13
|
|
Overall Study
NOT COMPLETED
|
7
|
7
|
Reasons for withdrawal
| Measure |
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.
|
Placebo
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.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
7
|
7
|
Baseline Characteristics
Alpha-Lipoic Acid in Preventing Hearing Loss in Cancer Patients Undergoing Treatment With Cisplatin
Baseline characteristics by cohort
| Measure |
Arm 1
n=19 Participants
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.
|
Arm 2
n=20 Participants
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.
|
Total
n=39 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Age, Continuous
|
62.0 years
STANDARD_DEVIATION 10.2 • n=99 Participants
|
60.6 years
STANDARD_DEVIATION 12.3 • n=107 Participants
|
61.2 years
STANDARD_DEVIATION 11.2 • n=206 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
38 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
19 participants
n=99 Participants
|
20 participants
n=107 Participants
|
39 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline measurement occurred prior to first cisplatin treatment session. Follow-up measurements occurred up to 3 months after last cisplatin treatment.Population: Intent-to-treat (ITT)
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.
Outcome measures
| Measure |
Arm 1
n=10 Participants
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.
|
Arm 2
n=13 Participants
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.
|
|---|---|---|
|
Ototoxicity Measurement
|
7 participants
|
7 participants
|
SECONDARY outcome
Timeframe: Baseline measurement occurred prior to first cisplatin treatment session. Follow-up measurements occurred up to 3 months after last cisplatin treatment.Population: Non-missing MDA measurements from 23 subjects in primary outcome analysis
Computed maximum increase relative to baseline for each subject = (max MDA during treatment) - baseline MDA level.
Outcome measures
| Measure |
Arm 1
n=10 Participants
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.
|
Arm 2
n=11 Participants
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.
|
|---|---|---|
|
Malondialdehyde (MDA) Levels
|
0.27 uM=micro-moles/liter
Standard Deviation 1.00
|
0.47 uM=micro-moles/liter
Standard Deviation 0.83
|
SECONDARY outcome
Timeframe: cisplatin treatment period between 10 weeks and up to 16 weeks.Population: Subjects from the original 39 recruited who had sufficient chemotherapy data recorded to measure cumulative dose.
Maximum cumulative dose of cisplatin (mg/m\^2) administered during the course of chemotherapy.
Outcome measures
| Measure |
Arm 1
n=19 Participants
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.
|
Arm 2
n=20 Participants
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.
|
|---|---|---|
|
Total Amount of Prescribed Cisplatin Dose Administered
|
239.7 mg/m^2
Standard Deviation 92.6
|
191.5 mg/m^2
Standard Deviation 110.5
|
Adverse Events
Arm 1
Serious events: 5 serious events
Other events: 3 other events
Deaths: 0 deaths
Arm 2
Serious events: 6 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm 1
n=19 participants at risk
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.
|
Arm 2
n=20 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
5.3%
1/19 • Number of events 1
|
10.0%
2/20 • Number of events 2
|
|
Gastrointestinal disorders
Nausea/vomitting
|
5.3%
1/19 • Number of events 1
|
0.00%
0/20
|
|
Blood and lymphatic system disorders
Blood transfusion
|
5.3%
1/19 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
|
Renal and urinary disorders
Acute Renal Failure
|
0.00%
0/19
|
15.0%
3/20 • Number of events 3
|
|
Endocrine disorders
Pancreatitis
|
0.00%
0/19
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Esophagitis
|
5.3%
1/19 • Number of events 1
|
0.00%
0/20
|
|
Infections and infestations
sceptic shock
|
5.3%
1/19 • Number of events 1
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
hypoxic respiratory failure
|
0.00%
0/19
|
5.0%
1/20 • Number of events 1
|
Other adverse events
| Measure |
Arm 1
n=19 participants at risk
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.
|
Arm 2
n=20 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Small bowel obstruction
|
0.00%
0/19
|
5.0%
1/20 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Spine pain
|
0.00%
0/19
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Distended abdomen
|
5.3%
1/19 • Number of events 1
|
0.00%
0/20
|
|
Cardiac disorders
Atrial Fibrillation
|
5.3%
1/19 • Number of events 1
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness
|
5.3%
1/19 • Number of events 1
|
0.00%
0/20
|
Additional Information
Dawn Konrad-Martin
VA RR&D National Center for Rehbilitative Auditory Research
Phone: 503-220-8262
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place