Repetitive Transcranial Magnetic Stimulation for Chronic Subjective Tinnitus

NCT03425045 | Completed

• 2 other identifiers: FNO-ENT-tinnitusMH CZ-DRO (FNOs/2015)
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Tinnitus, Subjective

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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.

  36 months

• 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.

  36 months

• 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.

  36 months

Secondary Outcomes (2)

• Improvement of depression - Beck Depression Inventory

  36 months

• Improvement of hearing loss - Fowler scoring

  36 months

Study Arms (3)

Repetitive Transcranial Magnetic Stimulation

EXPERIMENTAL

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

Procedure: Repetitive Transcranial Magnetic Stimulation

Sham stimulation

SHAM COMPARATOR

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

Procedure: Sham stimulation

Ginkgo Biloba Extract

ACTIVE COMPARATOR

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

Drug: Ginkgo Biloba Extract

Interventions

Repetitive Transcranial Magnetic Stimulation PROCEDURE

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.

Repetitive Transcranial Magnetic Stimulation

Sham stimulation PROCEDURE

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.

Sham stimulation

Ginkgo Biloba Extract DRUG

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

Ginkgo Biloba Extract

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Ostrava: lead

Study Sites (1)

University Hospital Ostrava

Ostrava, Moravian-Silesian Region, 70852, Czechia

Location

Related Publications (19)

• 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.

  PMID: 17114152 BACKGROUND

• 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.

  PMID: 21221011 BACKGROUND

• 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.

  PMID: 25034472 BACKGROUND

• 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.

  PMID: 23781982 BACKGROUND

• 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.

  PMID: 18359361 BACKGROUND

• 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.

  PMID: 22069382 BACKGROUND

• 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.

  PMID: 22853891 BACKGROUND

• 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.

  PMID: 23968498 BACKGROUND

• 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.

  PMID: 23229756 BACKGROUND

• 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.

  PMID: 22909265 BACKGROUND

• 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.

  PMID: 24157459 BACKGROUND

• 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.

  PMID: 25017670 BACKGROUND

• 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.

  PMID: 22539568 BACKGROUND

• 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.

  PMID: 26422238 BACKGROUND

• 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.

  PMID: 17903575 BACKGROUND

• 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.

  PMID: 18202212 BACKGROUND

• 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.

  PMID: 19614962 BACKGROUND

• 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.

  PMID: 20158510 BACKGROUND

• 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.

  PMID: 8630207 BACKGROUND

Related Links

• The American Academy of Audiology is the world's largest professional organization of, by, and for audiologists.

MeSH Terms

Conditions

Tinnitus; Depression

Interventions

Transcranial Magnetic Stimulation; Ginkgo biloba extract

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Michal Bar, Ass.Prof.,MD,PhD

  University Hospital Ostrava

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The study subjects and outcomes assessors will be masked, the investigator will know which treatment is being provided for which patient.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is designed as interventional, blinded, randomized, controlled trial with three parallel arms

Study Record Dates

• First Submitted: January 15, 2018
• First Posted: February 7, 2018
• Study Start: March 1, 2015
• Primary Completion: March 31, 2018
• Study Completion: March 31, 2018
• Last Updated: June 4, 2018

Record last verified: 2018-06

Locations

CZ (1)