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CompletedNCT03425045Updated Jun 4, 2018

Repetitive Transcranial Magnetic Stimulation for Chronic Subjective Tinnitus

An interventional study of Repetitive Transcranial Magnetic Stimulation and Sham stimulation in Tinnitus, Subjective, sponsored by University Hospital Ostrava. Completed at 1 site in Czechia. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2018-06-04.

Sponsored by University Hospital Ostrava · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
18 Years to 99 Years
Sex
All
01

Study summary

Therapy of subjective chronic primary tinnitus could be challenging. Repetitive transcranial magnetic stimulation (rTMS) is currently being tested for suppressing the symptoms. However, effect of stimulation remains controversial. The aim was to uncover real effect of rTMS stimulation for tinnitus treatment. There will be three groups, stimulation group, sham stimulation group and controlled group with medicament treatment. The investigators assume that combination of rTMS stimulation of dorsolateral prefrontal cortex and primary auditory cortex at both sides will be more efficient. The investigators considered a 10% improvement in the tinnitus questionnaire score and in the tinnitus masking to be clinically relevant.

Read the detailed description

Adult patients suffering from chronic subjective non-pulsatile primary unilateral or bilateral tinnitus for at least 6 months will be included in the study. Patients will be randomly assigned using a random number generation randomization method into rTMS stimulation group (group 1), sham stimulation group (group 2) and group with medicament therapy only (group 3). Dorsolateral prefrontal cortex (frequency 25 Hz; 300 pulses; 80% resting motor threshold=RMT) and primary auditory cortex on both sides (1 Hz; 1000 pulses; 110% RMT) will be stimulated in patients in rTMS stimulation group for 5 consecutive days. Both the patients and outcome assessor were blinded to the intervention group in which the patients (rTMS and shame stimulation group) belonged to. Medicament therapy in group 3 will consist of ginkgo biloba extract EGb 761 once a day for 6 months. There will be no medicament therapy for tinnitus in group 1 and 2. Tinnitus reaction questionnaire (TRQ), tinnitus handicap questionnaire (THQ), tinnitus handicap inventory (THI), Beck Depression Inventory (BDI), pure-tone audiometry with Fowler scoring of hearing loss and tinnitus analysis will be used for evaluation of tinnitus in all patients. Data will be recorded on the day patient is included in the study, during follow-up after 1 month and 6 months. Descriptive statistics, such as the arithmetic mean, standard deviation, and absolute and relative frequency tables, will be used for data processing. The Pearson's chi-squared test, Fisher's exact test, Kruskal-Wallis test and analysis of variance will be used for comparison. The statistical tests will be assessed using a significance level of 5%.

02

Conditions studied

  • Tinnitus, Subjective

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Keywords

  • chronic tinnitus
  • repetitive transcranial magnetic stimulation
  • hypacusion
  • depression
  • treatment
  • placebo
  • medication therapy
03

Who can participate

Ages eligible
18 Years to 99 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • subjective chronic non-pulsatile tinnitus lasting more than 6 months

Exclusion criteria

Exclusion Criteria:

  • head injury or brain surgery
  • epilepsy
  • organic brain lesion
  • Meniere's disease or fluctuating hearing loss
  • cochlear or bone-anchored hearing device implantation
  • history of suicide
  • pregnancy
  • therapy with anticonvulsants
  • antipsychotic medication
  • heart pacemaker implantation
  • rTMS performed in the past
  • not signing of the informed consent
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    Repetitive Transcranial Magnetic Stimulation

    Patients in this study arm will undergo the rTMS stimulation as described above.

    Procedure: Repetitive Transcranial Magnetic Stimulation

  • Sham comparator
    Sham stimulation

    Patients in this study arm will undergo the sham stimulation as described above.

    Procedure: Sham stimulation

  • Active comparator
    Ginkgo Biloba Extract

    Patients in this study arm will receive medication therapy as described above, without any rTMS or sham procedure.

    Drug: Ginkgo Biloba Extract

Interventions

  • ProcedureRepetitive Transcranial Magnetic Stimulation

    Patients randomised in Arm 1 will receive stimulation of the dorsolateral prefrontal cortex (frequency 25 Hz; 300 pulses; 80% resting motor threshold=RMT) and primary auditory cortex on both sides (1 Hz; 1000 pulses; 110% RMT) will be stimulated in patients in rTMS stimulation group for 5 consecutive days. No medication therapy will be provided for patients in this arm.

  • ProcedureSham stimulation

    Sham stimulation will be performed in patients randomised in Arm 2 of the study for 5 consecutive days. No medication therapy will be provided for patients in this arm.

  • DrugGinkgo Biloba Extract

    Patients randomised in Arm 3 of the study will receive medication therapy with Ginkgo biloba extract EGb 761 once a day for 6 months.

05

What researchers measure

Primary outcomes

  1. Tinnitus Reaction Questionnaire (TRQ)

    This questionnaire will be used to find out what sort of effects tinnitus has had on the lifestyle and general well-being of the patients. 10% improvement will be considered clinically relevant.

    Time frame: 36 months

  2. Tinnitus Handicap Questionnaire (THQ)

    This questionnaire has 27 questions and will be used to assess the degree of handicap that the tinnitus presents for the affected patients. 10% improvement will be considered clinically relevant.

    Time frame: 36 months

  3. Tinnitus Handicap Inventory (THI)

    The purpose of this questionnaire is to identify difficulties the affected patients may be experiencing because of tinnitus. 10% improvement of the score will be considered clinically relevant.

    Time frame: 36 months

Secondary outcomes

  1. Improvement of depression - Beck Depression Inventory

    Improvement of depressive symptoms in patients will be assessed using the Beck Depression Inventory (BDI) test.

    Time frame: 36 months

  2. Improvement of hearing loss - Fowler scoring

    Improvement of the hearing loss in patients will be assessed using the pure-tone audiometry with Fowler scoring of hearing loss (%).

    Time frame: 36 months

06

Study locations

1 site
  • University Hospital Ostrava
    Ostrava, Moravian-Silesian Region 70852, Czechia
07

References and documents

Publications

  • Folmer RL, Carroll JR, Rahim A, Shi Y, Hal Martin W. Effects of repetitive transcranial magnetic stimulation (rTMS) on chronic tinnitus. Acta Otolaryngol Suppl. 2006 Dec;(556):96-101. doi: 10.1080/03655230600895465. PubMed 17114152 ↗
  • Oberman L, Edwards D, Eldaief M, Pascual-Leone A. Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. J Clin Neurophysiol. 2011 Feb;28(1):67-74. doi: 10.1097/WNP.0b013e318205135f. PubMed 21221011 ↗
  • Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelainen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021. Epub 2014 Jun 5. PubMed 25034472 ↗
  • Kim BG, Kim DY, Kim SK, Kim JM, Baek SH, Moon IS. Comparison of the outcomes of repetitive transcranial magnetic stimulation to the ipsilateral and contralateral auditory cortex in unilateral tinnitus. Electromagn Biol Med. 2014 Sep;33(3):211-5. doi: 10.3109/15368378.2013.801353. Epub 2013 Jun 19. PubMed 23781982 ↗
  • Kleinjung T, Eichhammer P, Landgrebe M, Sand P, Hajak G, Steffens T, Strutz J, Langguth B. Combined temporal and prefrontal transcranial magnetic stimulation for tinnitus treatment: a pilot study. Otolaryngol Head Neck Surg. 2008 Apr;138(4):497-501. doi: 10.1016/j.otohns.2007.12.022. PubMed 18359361 ↗
  • Kreuzer PM, Landgrebe M, Schecklmann M, Poeppl TB, Vielsmeier V, Hajak G, Kleinjung T, Langguth B. Can Temporal Repetitive Transcranial Magnetic Stimulation be Enhanced by Targeting Affective Components of Tinnitus with Frontal rTMS? A Randomized Controlled Pilot Trial. Front Syst Neurosci. 2011 Nov 4;5:88. doi: 10.3389/fnsys.2011.00088. eCollection 2011. PubMed 22069382 ↗
  • De Ridder D, Song JJ, Vanneste S. Frontal cortex TMS for tinnitus. Brain Stimul. 2013 May;6(3):355-62. doi: 10.1016/j.brs.2012.07.002. Epub 2012 Jul 24. PubMed 22853891 ↗
  • Lehner A, Schecklmann M, Kreuzer PM, Poeppl TB, Rupprecht R, Langguth B. Comparing single-site with multisite rTMS for the treatment of chronic tinnitus - clinical effects and neuroscientific insights: study protocol for a randomized controlled trial. Trials. 2013 Aug 23;14:269. doi: 10.1186/1745-6215-14-269. Erratum In: Trials. 2014;5:148. PubMed 23968498 ↗
  • Lehner A, Schecklmann M, Poeppl TB, Kreuzer PM, Vielsmeier V, Rupprecht R, Landgrebe M, Langguth B. Multisite rTMS for the treatment of chronic tinnitus: stimulation of the cortical tinnitus network--a pilot study. Brain Topogr. 2013 Jul;26(3):501-10. doi: 10.1007/s10548-012-0268-4. Epub 2012 Dec 11. PubMed 23229756 ↗
  • Langguth B, Landgrebe M, Frank E, Schecklmann M, Sand PG, Vielsmeier V, Hajak G, Kleinjung T. Efficacy of different protocols of transcranial magnetic stimulation for the treatment of tinnitus: Pooled analysis of two randomized controlled studies. World J Biol Psychiatry. 2014 May;15(4):276-85. doi: 10.3109/15622975.2012.708438. Epub 2012 Aug 22. PubMed 22909265 ↗
  • Hoekstra CE, Versnel H, Neggers SF, Niesten ME, van Zanten GA. Bilateral low-frequency repetitive transcranial magnetic stimulation of the auditory cortex in tinnitus patients is not effective: a randomised controlled trial. Audiol Neurootol. 2013;18(6):362-73. doi: 10.1159/000354977. Epub 2013 Oct 19. PubMed 24157459 ↗
  • Engelhardt J, Dauman R, Arne P, Allard M, Dauman N, Branchard O, Perez P, Germain C, Caire F, Bonnard D, Cuny E. Effect of chronic cortical stimulation on chronic severe tinnitus: a prospective randomized double-blind cross-over trial and long-term follow up. Brain Stimul. 2014 Sep-Oct;7(5):694-700. doi: 10.1016/j.brs.2014.05.008. Epub 2014 Jun 4. PubMed 25017670 ↗
  • Plewnia C, Vonthein R, Wasserka B, Arfeller C, Naumann A, Schraven SP, Plontke SK. Treatment of chronic tinnitus with theta burst stimulation: a randomized controlled trial. Neurology. 2012 May 22;78(21):1628-34. doi: 10.1212/WNL.0b013e3182574ef9. Epub 2012 Apr 25. PubMed 22539568 ↗
  • Roland LT, Peelle JE, Kallogjeri D, Nicklaus J, Piccirillo JF. The effect of noninvasive brain stimulation on neural connectivity in Tinnitus: A randomized trial. Laryngoscope. 2016 May;126(5):1201-6. doi: 10.1002/lary.25650. Epub 2015 Sep 30. PubMed 26422238 ↗
  • Kleinjung T, Steffens T, Sand P, Murthum T, Hajak G, Strutz J, Langguth B, Eichhammer P. Which tinnitus patients benefit from transcranial magnetic stimulation? Otolaryngol Head Neck Surg. 2007 Oct;137(4):589-95. doi: 10.1016/j.otohns.2006.12.007. PubMed 17903575 ↗
  • Khedr EM, Rothwell JC, Ahmed MA, El-Atar A. Effect of daily repetitive transcranial magnetic stimulation for treatment of tinnitus: comparison of different stimulus frequencies. J Neurol Neurosurg Psychiatry. 2008 Feb;79(2):212-5. doi: 10.1136/jnnp.2007.127712. PubMed 18202212 ↗
  • Marcondes RA, Sanchez TG, Kii MA, Ono CR, Buchpiguel CA, Langguth B, Marcolin MA. Repetitive transcranial magnetic stimulation improve tinnitus in normal hearing patients: a double-blind controlled, clinical and neuroimaging outcome study. Eur J Neurol. 2010 Jan;17(1):38-44. doi: 10.1111/j.1468-1331.2009.02730.x. Epub 2009 Jul 9. PubMed 19614962 ↗
  • Frank G, Kleinjung T, Landgrebe M, Vielsmeier V, Steffenhagen C, Burger J, Frank E, Vollberg G, Hajak G, Langguth B. Left temporal low-frequency rTMS for the treatment of tinnitus: clinical predictors of treatment outcome--a retrospective study. Eur J Neurol. 2010 Jul;17(7):951-6. doi: 10.1111/j.1468-1331.2010.02956.x. Epub 2010 Feb 10. PubMed 20158510 ↗
  • Newman CW, Jacobson GP, Spitzer JB. Development of the Tinnitus Handicap Inventory. Arch Otolaryngol Head Neck Surg. 1996 Feb;122(2):143-8. doi: 10.1001/archotol.1996.01890140029007. PubMed 8630207 ↗

Individual participant data

Plan to share: Undecided — The plan to share IPD to other researchers has not been decided yet.

08

Registry details

Key details

Study ID
NCT03425045
Lead sponsor
University Hospital Ostrava
Responsible party
Sponsor
First posted
Feb 7, 2018
Start date
Mar 1, 2015
Primary completion
Mar 31, 2018
Completion
Mar 31, 2018
Last update
Jun 4, 2018

Study contacts

Michal Bar, Ass.Prof.,MD,PhD
principal investigator · University Hospital Ostrava

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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