OtotoxicityPhase 2NCT01139281
The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
A Phase 2 study testing Ginkgo Biloba Extract (GBE761) in people with Ototoxicity and Hearing Loss, run by University of Brasilia at 1 site in Brazil.
Trial summary
The proposal of this study was to evaluate in human beings, using distortion product otoacoustic emission (DPOAE) test, the action of ginkgo biloba extract (GBE761)as a possible ear protective against cisplatin (CDDP) induced hearing loss. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ototoxicity, Hearing Loss
- What is being tested?
- Ginkgo Biloba Extract (GBE761)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteBrazil
- Study dates
- Jun 2007to Jun 2008
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Over the age of eighteen
- Patients that will begin treatment with cisplatin
- No prior treatment with cisplatin
Who cannot join
- Individuals with middle ear, cochlear or retrocochlear disease
- Presence of changes in pure tone audiometry and/or distortion-product otoacoustic emissions
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Hospital de Base do Distrito Federal (HBDF)
Brasília, Federal District, 70000-000
About this study
Official title: The Protective Effect of Ginkgo Biloba Extract on Cisplatin-Induced Ototoxicity in Humans Beings Evaluated by Distortion Product Otoacoustic Emissions
The proposal of this study was to evaluate in human beings, using distortion product otoacoustic emission (DPOAE) test, the action of ginkgo biloba extract (GBE761)as a possible ear protective against cisplatin (CDDP) induced hearing loss.
Read the detailed description
The ototoxicity is an alteration caused by drugs that compromises the auditory and vestibular functions. The cisplatin (CDDP) is a potent antineoplastic agent used for the treatment of cancer in both adults and children although it has several side effects. Current opinion is that cisplatin ototoxicity occurs due to alterations in the antioxidant system of the outer hair cells (OHC) of the cochlea. The distortion-product otoacoustic emissions (DPOAE) has been showed to be a sensitive test for diagnosis of OHC injury and has been used for monitoring treatment with ototoxic drugs. Because of their antioxidant properties, the ginkgo biloba extract (GBE761) was evaluated in human beings as a possible ear protective against cisplatin induced hearing loss, using DPOAE test.
- Conditions
- Ototoxicity, Hearing Loss
- Being tested
- Ginkgo Biloba Extract (GBE761), Placebo
- Keywords
- Ear protection, Ginkgo Biloba Extract, Distortion-product otoacoustic emission, Ototoxicity, Cisplatin
- Medical subject headings
- Ototoxicity, Hearing Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ginkgo Biloba Extract (GBE761)Drug
Also called Study Group
The subjects were randomized and allocated in two groups: Control Group(CG) and Study Group(SG). the study group received GBE761(120mg twice a day) plus cisplatin and was guided to ingest GBE761 just before initial cisplatin dosage. The maximum cumulative cisplatin dosage was 300mg/m². They were followed up for ninety days. Comparisons were made between baseline distortion-product otoacoustic emissions measurements and those DPOAE records after maximum cumulative cisplatin dosage.
PlaceboDrug
Also called Control Group
The subjects were randomized and allocated in two groups: control group and study group. The control group received placebo plus cisplatin and was guided to ingest Placebo just before initial cisplatin dosage. The maximum cumulative cisplatin dosage was 300mg/m². They were followed up for ninety days. Comparisons were made between baseline distortion-product otoacoustic emissions measurements and those DPOAE records after maximum cumulative cisplatin dosage.
| Study group | Role | What they receive |
|---|---|---|
| Study Group | Active comparator | The Study Group(SG) received Ginkgo biloba extract(GBE761)(240mg/day)plus cisplatin(CDDP) Receives: Drug: Ginkgo Biloba Extract (GBE761) |
| Control Group(CG) | Placebo comparator | The Control Group received Placebo plus CDDP Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
the effect of GBE761 as a possible protector against cisplatin (CDDP) induced hearing loss was evaluated through the DPOAE. Comparisons were made between baseline measurements and those records after maximum cumulative CDDP dosage.
The protective effect of GBE761 on CDDP induced ototoxicity in human beings was evaluated with DPOAE mean amplitudes and signal-to-noise ratio (SNR) values at in the frequencies ranging from 1 to 8KHz in the study and control groups, between before and after cumulative CDDP injections, in order to evaluate the significant differences in DPOAE results, and so to differentiate hearing status ( normal hearing or hearing loss) while the subjects were taking GBE or placebo.
Measured: the patients were followed about ninety days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2010 (estimated)
- Study startJun 2007
- Primary completionJun 2008
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (56)Papers the sponsor has linked to this study.
- 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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Brasilia
- Sponsor type
- University, hospital or other
- Investigators
- Mirela A Dias, Principal investigator, University of BrasiliaCarlos CP Oliveira, Study chair, University of Brasilia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01139281
- Sponsor's protocol ID
- CEPSESDF-024-07
- Status last verified
- May 2010
- First submitted
- 1 Jun 2010
- Last updated
- 8 Jun 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Biro K, Noszek L, Prekopp P, Nagyivanyi K, Geczi L, Gaudi I, Bodrogi I. Characteristics and risk factors of cisplatin-induced ototoxicity in testicular cancer patients detected by distortion product otoacoustic emission. Oncology. 2006;70(3):177-84. doi: 10.1159/000093776. Epub 2006 Jun 2.
PubMed 16757924Blakley BW, Myers SF. Patterns of hearing loss resulting from cis-platinum therapy. Otolaryngol Head Neck Surg. 1993 Sep;109(3 Pt 1):385-91. doi: 10.1177/019459989310900302.
PubMed 8414553Bridi R, Crossetti FP, Steffen VM, Henriques AT. The antioxidant activity of standardized extract of Ginkgo biloba (EGb 761) in rats. Phytother Res. 2001 Aug;15(5):449-51. doi: 10.1002/ptr.814.
PubMed 11507743Christen Y, Maixent JM. What is Ginkgo biloba extract EGb 761? An overview--from molecular biology to clinical medicine. Cell Mol Biol (Noisy-le-grand). 2002 Sep;48(6):601-11.
PubMed 12396070Dhooge I, Dhooge C, Geukens S, De Clerck B, De Vel E, Vinck BM. Distortion product otoacoustic emissions: an objective technique for the screening of hearing loss in children treated with platin derivatives. Int J Audiol. 2006 Jun;45(6):337-43. doi: 10.1080/14992020600582117.
PubMed 16777780Gardner CD, Zehnder JL, Rigby AJ, Nicholus JR, Farquhar JW. Effect of Ginkgo biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: a randomized clinical trial. Blood Coagul Fibrinolysis. 2007 Dec;18(8):787-93. doi: 10.1097/MBC.0b013e3282f102b1.
PubMed 17982321Gorga MP, Neely ST, Ohlrich B, Hoover B, Redner J, Peters J. From laboratory to clinic: a large scale study of distortion product otoacoustic emissions in ears with normal hearing and ears with hearing loss. Ear Hear. 1997 Dec;18(6):440-55. doi: 10.1097/00003446-199712000-00003.
PubMed 9416447Gorga MP, Stover L, Neely ST, Montoya D. The use of cumulative distributions to determine critical values and levels of confidence for clinical distortion product otoacoustic emission measurements. J Acoust Soc Am. 1996 Aug;100(2 Pt 1):968-77. doi: 10.1121/1.416208.
PubMed 8759950Hatzopoulos S, Di Stefano M, Campbell KC, Falgione D, Ricci D, Rosignoli M, Finesso M, Albertin A, Previati M, Capitani S, Martini A. Cisplatin ototoxicity in the Sprague Dawley rat evaluated by distortion product otoacoustic emissions. Audiology. 2001 Sep-Oct;40(5):253-64.
PubMed 11688544Hibatallah J, Carduner C, Poelman MC. In-vivo and in-vitro assessment of the free-radical-scavenger activity of Ginkgo flavone glycosides at high concentration. J Pharm Pharmacol. 1999 Dec;51(12):1435-40. doi: 10.1211/0022357991777083.
PubMed 10678500Huang T, Cheng AG, Stupak H, Liu W, Kim A, Staecker H, Lefebvre PP, Malgrange B, Kopke R, Moonen G, Van De Water TR. Oxidative stress-induced apoptosis of cochlear sensory cells: otoprotective strategies. Int J Dev Neurosci. 2000 Apr-Jun;18(2-3):259-70. doi: 10.1016/s0736-5748(99)00094-5.
PubMed 10715580Rybak LP, Husain K, Morris C, Whitworth C, Somani S. Effect of protective agents against cisplatin ototoxicity. Am J Otol. 2000 Jul;21(4):513-20.
PubMed 10912697Kaltenbach JA, Church MW, Blakley BW, McCaslin DL, Burgio DL. Comparison of five agents in protecting the cochlea against the ototoxic effects of cisplatin in the hamster. Otolaryngol Head Neck Surg. 1997 Nov;117(5):493-500. doi: 10.1016/S0194-59989770020-2.
PubMed 9374173Kobuchi H, Droy-Lefaix MT, Christen Y, Packer L. Ginkgo biloba extract (EGb 761): inhibitory effect on nitric oxide production in the macrophage cell line RAW 264.7. Biochem Pharmacol. 1997 Mar 21;53(6):897-903. doi: 10.1016/s0006-2952(96)00873-8.
PubMed 9113109Meyerhoff WL, Maale GE, Yellin W, Roland PS. Audiologic threshold monitoring of patients receiving ototoxic drugs. Preliminary report. Ann Otol Rhinol Laryngol. 1989 Dec;98(12 Pt 1):950-4. doi: 10.1177/000348948909801206.
PubMed 2589763
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Protective Effect of Ginkgo Biloba Extract on Cisplatin-Induced Ototoxicity in Humans Beings Evaluated by Distortion Product Otoacoustic Emissions
- ClinicalTrials.gov ID
- NCT01139281
- Acronym / sponsor ID
- CEPSESDF-024-07
- Conditions
- Ototoxicity, Hearing Loss
- Keywords
- Ear protection, Ginkgo Biloba Extract, Distortion-product otoacoustic emission, Ototoxicity, Cisplatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of BrasiliaUniversity, hospital or other
- Study start
- Jun 2007
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 8 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposal of this study was to evaluate in human beings, using distortion product otoacoustic emission (DPOAE) test, the action of ginkgo biloba extract (GBE761)as a possible ear protective against cisplatin (CDDP) induced hearing loss.
Detailed description
The ototoxicity is an alteration caused by drugs that compromises the auditory and vestibular functions. The cisplatin (CDDP) is a potent antineoplastic agent used for the treatment of cancer in both adults and children although it has several side effects. Current opinion is that cisplatin ototoxicity occurs due to alterations in the antioxidant system of the outer hair cells (OHC) of the cochlea. The distortion-product otoacoustic emissions (DPOAE) has been showed to be a sensitive test for diagnosis of OHC injury and has been used for monitoring treatment with ototoxic drugs. Because of their antioxidant properties, the ginkgo biloba extract (GBE761) was evaluated in human beings as a possible ear protective against cisplatin induced hearing loss, using DPOAE test.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study Group | Active comparator | Drug: Ginkgo Biloba Extract (GBE761)The Study Group(SG) received Ginkgo biloba extract(GBE761)(240mg/day)plus cisplatin(CDDP) |
| Control Group(CG) | Placebo comparator | Drug: PlaceboThe Control Group received Placebo plus CDDP |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Over the age of eighteen
- Patients that will begin treatment with cisplatin
- No prior treatment with cisplatin
Key exclusion criteria (2 listed)
- Individuals with middle ear, cochlear or retrocochlear disease
- Presence of changes in pure tone audiometry and/or distortion-product otoacoustic emissions
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 |
|---|---|---|
| Ginkgo Biloba Extract (GBE761)Also: Study GroupThe subjects were randomized and allocated in two groups: Control Group(CG) and Study Group(SG). the study group received GBE761(120mg twice a day) plus cisplatin and was guided to ingest GBE761 just before initial cisplatin dosage. The maximum cumulative cisplatin dosage was 300mg/m². They were followed up for ninety days. Comparisons were made between baseline distortion-product otoacoustic emissions measurements and those DPOAE records after maximum cumulative cisplatin dosage. | Drug | Study Group |
| PlaceboAlso: Control GroupThe subjects were randomized and allocated in two groups: control group and study group. The control group received placebo plus cisplatin and was guided to ingest Placebo just before initial cisplatin dosage. The maximum cumulative cisplatin dosage was 300mg/m². They were followed up for ninety days. Comparisons were made between baseline distortion-product otoacoustic emissions measurements and those DPOAE records after maximum cumulative cisplatin dosage. | Drug | Control Group(CG) |
Primary outcome
the effect of GBE761 as a possible protector against cisplatin (CDDP) induced hearing loss was evaluated through the DPOAE. Comparisons were made between baseline measurements and those records after maximum cumulative CDDP dosage.
Time frame: the patients were followed about ninety days
The protective effect of GBE761 on CDDP induced ototoxicity in human beings was evaluated with DPOAE mean amplitudes and signal-to-noise ratio (SNR) values at in the frequencies ranging from 1 to 8KHz in the study and control groups, between before and after cumulative CDDP injections, in order to evaluate the significant differences in DPOAE results, and so to differentiate hearing status ( normal hearing or hearing loss) while the subjects were taking GBE or placebo.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2010.
- Background: PubMed 16757924Biro K, Noszek L, Prekopp P, Nagyivanyi K, Geczi L, Gaudi I, Bodrogi I. Characteristics and risk factors of cisplatin-induced ototoxicity in testicular cancer patients detected by distortion product otoacoustic emission. Oncology. 2006;70(3):177-84. doi: 10.1159/000093776. Epub 2006 Jun 2.
- Background: PubMed 8414553Blakley BW, Myers SF. Patterns of hearing loss resulting from cis-platinum therapy. Otolaryngol Head Neck Surg. 1993 Sep;109(3 Pt 1):385-91. doi: 10.1177/019459989310900302.
- Background: PubMed 11507743Bridi R, Crossetti FP, Steffen VM, Henriques AT. The antioxidant activity of standardized extract of Ginkgo biloba (EGb 761) in rats. Phytother Res. 2001 Aug;15(5):449-51. doi: 10.1002/ptr.814.
- Background: PubMed 12396070Christen Y, Maixent JM. What is Ginkgo biloba extract EGb 761? An overview--from molecular biology to clinical medicine. Cell Mol Biol (Noisy-le-grand). 2002 Sep;48(6):601-11.
- Background: PubMed 16777780Dhooge I, Dhooge C, Geukens S, De Clerck B, De Vel E, Vinck BM. Distortion product otoacoustic emissions: an objective technique for the screening of hearing loss in children treated with platin derivatives. Int J Audiol. 2006 Jun;45(6):337-43. doi: 10.1080/14992020600582117.
- Background: PubMed 17982321Gardner CD, Zehnder JL, Rigby AJ, Nicholus JR, Farquhar JW. Effect of Ginkgo biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: a randomized clinical trial. Blood Coagul Fibrinolysis. 2007 Dec;18(8):787-93. doi: 10.1097/MBC.0b013e3282f102b1.
- Background: PubMed 9416447Gorga MP, Neely ST, Ohlrich B, Hoover B, Redner J, Peters J. From laboratory to clinic: a large scale study of distortion product otoacoustic emissions in ears with normal hearing and ears with hearing loss. Ear Hear. 1997 Dec;18(6):440-55. doi: 10.1097/00003446-199712000-00003.
- Background: PubMed 8759950Gorga MP, Stover L, Neely ST, Montoya D. The use of cumulative distributions to determine critical values and levels of confidence for clinical distortion product otoacoustic emission measurements. J Acoust Soc Am. 1996 Aug;100(2 Pt 1):968-77. doi: 10.1121/1.416208.
- Background: PubMed 11688544Hatzopoulos S, Di Stefano M, Campbell KC, Falgione D, Ricci D, Rosignoli M, Finesso M, Albertin A, Previati M, Capitani S, Martini A. Cisplatin ototoxicity in the Sprague Dawley rat evaluated by distortion product otoacoustic emissions. Audiology. 2001 Sep-Oct;40(5):253-64.
- Background: PubMed 10678500Hibatallah J, Carduner C, Poelman MC. In-vivo and in-vitro assessment of the free-radical-scavenger activity of Ginkgo flavone glycosides at high concentration. J Pharm Pharmacol. 1999 Dec;51(12):1435-40. doi: 10.1211/0022357991777083.
- Background: PubMed 10715580Huang T, Cheng AG, Stupak H, Liu W, Kim A, Staecker H, Lefebvre PP, Malgrange B, Kopke R, Moonen G, Van De Water TR. Oxidative stress-induced apoptosis of cochlear sensory cells: otoprotective strategies. Int J Dev Neurosci. 2000 Apr-Jun;18(2-3):259-70. doi: 10.1016/s0736-5748(99)00094-5.
- Background: PubMed 10912697Rybak LP, Husain K, Morris C, Whitworth C, Somani S. Effect of protective agents against cisplatin ototoxicity. Am J Otol. 2000 Jul;21(4):513-20.
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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.
Mirela A Dias principal investigator
University of Brasilia
Carlos CP Oliveira study chair
University of Brasilia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ginkgo Biloba Extract (GBE761) in people with Ototoxicity and Hearing Loss, run by University of Brasilia at 1 site in Brazil.
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 3 inclusion and 2 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 8 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
the effect of GBE761 as a possible protector against cisplatin (CDDP) induced hearing loss was evaluated through the DPOAE. Comparisons were made between baseline measurements and those records after maximum cumulative CDDP dosage. (time frame: the patients were followed about ninety days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01139281, which also lists 56 linked publications.
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 8 Jun 2010.