Plain English Summary
Background and study aims
Tinnitus is where a person experiences a ringing or buzzing sound in one or both ears. It is not regarded as an illness in itself but as a symptom of different diseases. In most cases tinnitus is associated with damage to the hearing system, although it can also be associated with other factors, such as some head injuries, exposure to certain drugs, nerve damage or blood-flow problems. EGb 761® is a dry extract of Ginkgo biloba (maidenhair tree) which may be used for tinnitus treatment. All the clinical findings up to date suggest that EGb 761® may not only be effective for tinnitus symptoms, but also help improve feelings of low mood or anxiety associated with tinnitus. Depending on the cause, influence of risk factors, symptom characteristics and chronicity (length of the symptoms), EGb 761® may be more or less effective. The aim of this study is therefore to explore what influences the effectiveness of treatment with EGb 761®.
Who can participate?
Adults with long term (chronic) tinnitus.
What does the trial involve?
After a screening period of 7 consecutive days where medical history and tinnitus symptoms are recorded, all participants receive tablets containing EGb 761® to take twice a day for 24 weeks. Throughout the study and side effects from the medication are monitored by the patient and care team. After 12 and 24 weeks, participants complete a number of questionnaires in order to find out if the medication has helped reduce their symptoms.
What are the possible benefits and risks of participating?
All participants will receive EGb 761® treatment, which is expected to help reduce or cure their tinnitus symptoms. Therefore, participants may benefit from an improvement in their quality of life. They may also benefit from a detailed and wide tinnitus diagnostic. Blood tests may cause mild pain and can provoke bruises or tenderness in the extraction area. As EGb 761® is well tolerated according to the data gathered so far, there is no major risk to taking EGb 761®. There is also a small risk of upset stomach, headache and allergic skin reactions (usually mild). There is also a risk that bleeding disorders may also occur during treatment with EGb 761®.
Where is the study run from?
Centrum Medyczne LIMED (lead centre) and 11 other medical centres in Poland (Poland)
When is the study starting and how long is it expected to run for?
December 2015 to May 2018.
Who is funding the trial?
Dr. Willmar Schwabe GmbH & Co. KG (Germany)
Who is the main contact?
1. Mrs Annette Wassmer (public)
2. Dr Robert Hoerr (scientific)
Trial website
Contact information
Type
Public
Primary contact
Mrs Annette Wassmer
ORCID ID
Contact details
Dr. Willmar Schwabe GmbH & Co. KG
Willmar-Schwabe-Str. 4
Karlsruhe
76227
Germany
Type
Scientific
Additional contact
Dr Robert Hoerr
ORCID ID
http://orcid.org/0000-0002-9255-7679
Contact details
Dr. Willmar Schwabe GmbH & Co. KG
Willmar-Schwabe-Str. 4
Karlsruhe
76227
Germany
Additional identifiers
EudraCT number
2016-000315-32
ClinicalTrials.gov number
Protocol/serial number
523079.01.113
Study information
Scientific title
Clinical trial to explore treatment effects of Ginkgo biloba extract EGb 761® in patients with chronic tinnitus and effect modification by etiology, biological factors and concomitant pathologies
Acronym
Study hypothesis
The aim of this study is to explore whether causes, risk factors, chronicity, characteristics of tinnitus and accompanying features influence the treatment effect of EGb 761® in terms of improvement and response rates and to identify groups of patients that benefit most of EGb 761® treatment.
Ethics approval
Ethics Committee at Silesian Medical Chamber in Katowice, 15/06/2016, ref: 23/2016
Study design
Multi-centre uncontrolled open-label explorative phase IIb clinical trial
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Chronic tinnitus
Intervention
The trial involves 175 participants (male and female). The trial duration per participant is maximum of 26 weeks. Every patient receives 120 mg EGb 761® film coated tablets twice daily during the 24 treatment weeks. All patients undergo the following scheduled visits:
Screening visit: day -7 to day 0, medical history, tinnitus diagnostic (ears-nose-throat examinations, pure tone audiometry, determination of tinnitus loudness and frequency, tinnitus masking, noise discomfort level, safety laboratory tests, electrocardiogram (ECG), vital signs, physical examination
Baseline visit: Day 0, start treatment with EGb 761®, patient questionnaires (TQ, THI, HADS, PSQ, SDS, tinnitus loudness and annoyance), concomitant medications, adverse events
Week 6 Call: Week 6 ± 1, concomitant medications, adverse events
Week 12 Visit: Week 12 ± 1, patient questionnaires, concomitant medications, adverse events
Week 18 Call: Week 18 ±1, concomitant medications, adverse events
Week 24 Visit: Week 24 ± 1, tinnitus diagnostic (ears-nose-throat examinations, audiometry), patient questionnaires, concomitant medications, adverse events, safety laboratory tests, electrocardiogram (ECG), vital signs, physical examination
Intervention type
Drug
Phase
Drug names
Film-coated tablets containing 120mg EGb 761® (Ginkgo biloba extract)
Primary outcome measures
1. Effectiveness is measured using the Tinnitus Questionnaire (TQ) at baseline, 12 and 24 weeks
2. Effectiveness is measured using the Tinnitus Handicap Inventory (THI) at baseline, 12 and 24 weeks
3. Effectiveness is measured using the 11-point box scales for tinnitus loudness and annoyance at baseline, 12 and 24 weeks
4. Effectiveness is measured using the Pure tone audiometry at screening at 24 weeks
5. Effectiveness is measured using the Determination of tinnitus loudness at screening at 24 weeks
6. Anxiety and Depression are measured using the Hospital Anxiety and Depression Scale (HADS) at baseline, 12 and 24 weeks
7. Stress is measured using the Perceived Stress Questionnaire (PSQ) at baseline, 12 and 24 weeks
8. Effectiveness is measured using the Sheehan Disability Scale (SDS) at baseline, 12 and 24 weeks
Secondary outcome measures
1. Serious (SAEs) and non-serious adverse events (AEs) are spontaneously reported by the patient or observed by the investigator continuously throughout the whole trial
2. Vital signs (blood pressure, pulse rate) will be measured in sitting position at baseline, 12 and 24 weeks
3. Safety laboratory results (hematology, coagulation, clinical chemistry and urinalysis) are measured via blood and urine samples at screening and 24 weeks
Overall trial start date
15/12/2015
Overall trial end date
19/12/2017
Reason abandoned
Eligibility
Participant inclusion criteria
1. Outpatient male or female patient at least 18 years old
2. Chronic tinnitus
2.1. May be unilateral or bilateral, with or without concomitant hearing loss
2.2. Grade according to Biesinger is 2 or 3*
2.3. Duration of at least 3 months
3. Written informed consent to participate in the clinical trial, to trial-related treatment and to data recording in accordance with applicable laws
*Grade 2: The tinnitus is mainly perceived in silence and is disturbing under stress and strain.
Grade 3: The tinnitus causes permanent impairment in personal and occupational spheres. Emotional, cognitive and somatic disorders are present.
Participant type
Patient
Age group
Mixed
Gender
Both
Target number of participants
175
Participant exclusion criteria
1. Participation in another experimental drug trial at the same time or within the past 4 weeks before the baseline visit
2. Tinnitus due to Ménière's disease, vestibular schwannoma or otosclerosis
3. Any other drug treatments for tinnitus taken currently or within 2 weeks before the baseline visit
4. Gingko biloba preparation for any reason taken currently or within 4 weeks before the baseline visit
5. Cognitive behavioral therapy or tinnitus retraining therapy started within 6 months prior to the baseline visit or planned to be started during the course of the trial
6. Acute or chronic otitis media or acute vestibular neuritis
7. Ongoing psychiatric disorder, such as major depression, generalized anxiety disorder, schizophrenia, etc.
Of note: Symptoms of depression or anxiety or other behavioral or psychological symptoms at sub-syndromal level and not requiring treatment with psychotropic drugs are permitted.
8. Ongoing severe cardiac or circulatory disorder:
8.1. Severe (Canadian Cardiovascular Society stage IV) or unstable angina pectoris
8.2. Decompensated congestive heart failure (NYHA stage IV)
8.3. Uncontrolled hypertension with systolic blood pressure above 180 mmHg and / or diastolic blood pressure above 115 mmHg
8.4. Clinically significant cardiac arrhythmias (Lown classes IVb and V, bifascicular bundle branch block)
9. Severe renal or hepatic dysfunction (defined by serum creatinine or serum ASAT, ALAT or gamma-GT above 3 times the upper limit of the reference range in the anamnesis)
10. Ongoing uncontrolled endocrine or hematological disorder
11. Intake of drugs not permitted during participation in the trial, in particular, psychoactive drugs, systemic acting perfusion-enhancing drugs, cognition enhancing drugs, systemic acting anti-cholinergic drugs, regular use of anticoagulants (platelet aggregation inhibitors permitted) during the 2 weeks prior to the baseline visit
12. Ongoing hemorrhagic diathesis or coagulation disorder
13. Seizure within 2 years prior to Baseline Visit or regular use of anticonvulsive drugs
14. Active malignant disease (exception: prostate cancer which does not require other than hormone treatment within the next 6 months).
15. Known hypersensitivity to Ginkgo biloba extract or to excipients contained in the tablets
16. Active peptic ulcer disease or any gastrointestinal disease with potential impairment of the absorption of orally applied drugs (e.g. Billroth I/II, Crohn's disease, ulcerative colitis, any kind of enterectomy)
17. Female patients of childbearing potential without safe contraception (any form of hormonal contraception, intrauterine devices, sexual abstinence and partner sterilization are considered sufficiently safe when used consistently and correctly; child-bearing potential can be denied in case of postmenopausal state for at least 2 years, hysterectomy, bilateral tubal ligation or bilateral oophorectomy)
18. Planned surgical intervention requiring hospitalization during the clinical trial
19. Previous inclusion in the present clinical trial
20. Incapability of understanding nature, meaning and consequences of the clinical trial
21. Patient unable to read and / or write
22. Patients in custody by juridical or official order
23. Patients who are members of the staff of the trial center, staff of the sponsor or involved Clinical Research Organizations (CROs), the investigator him- / herself or close relatives of the investigator
Recruitment start date
15/11/2016
Recruitment end date
31/08/2017
Locations
Countries of recruitment
Poland
Trial participating centre
Centrum Medyczne LIMED
Tylna 12
Tarnowskie Góry
42-600
Poland
Trial participating centre
Grażyna Pulka Specjalistyczny Ośrodek "ALL-MED"
Św. Marka 31/1
Kraków
31-024
Poland
Trial participating centre
Medical Center Larmed
ul. Lwowska 17 lok. 1 and 2
Kraków
30-548
Poland
Trial participating centre
Nutricare Sp. z o.o
Rydlówka 42 A/48
Kraków
30-363
Poland
Trial participating centre
Promed P.Łach R.Głowacki Spółka Jawna
ul. Entertainment 24a
Kraków
31-411
Poland
Trial participating centre
Centrum Medyczne Biotamed Morawska Barbara
ul. Vincent Fields 4a
Wieliczka
32-020
Poland
Trial participating centre
Centrum Słuchu I Mowy SP. Z O.O.
Łużycka 42
Kraków
30-658
Poland
Trial participating centre
Centrum Słuchu I Mowy SP. Z O.O.
Mokra 7
Kajetany
Nadarzyn
05-830
Poland
Trial participating centre
Centrum Słuchu I Mowy SP. Z O.O.
Nasypowa 18
Katowice
40-551
Poland
Trial participating centre
Indywidualna Specjalistyczna Praktyka Lekarska Alergologialaryngologia
Sienkiewicza 13
Kęty
32-650
Poland
Trial participating centre
Audiofonika Aparaty Słucowe Przemysław Śpiewak SP.J.
Karpacka 4
Bielsko-Biała
43-316
Poland
Trial participating centre
Specjalistyczna Praktyka Lekarska
Niedurnego 50 d
Ruda Slaska
41-709
Poland
Funders
Funder type
Industry
Funder name
Dr. Willmar Schwabe GmbH & Co. KG
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal.
IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
31/05/2019
Participant level data
To be made available at a later date
Results - basic reporting
Publication summary