Subjective TinnitusPhase 2CTRWUNCT00567892

Collaborative Tinnitus Research at Washington University

A Phase 2 study testing rTMS in people with Subjective Tinnitus, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Subjective Tinnitus
What is being tested?: rTMS
Type of treatment: Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 55 participants
Where: 1 siteUnited States
Study dates: Jan 2008to Jun 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Men and women between the ages of 18 and 60 years.
Subjective, unilateral or bilateral, non-pulsatile tinnitus of 6 month's duration or greater.
Tinnitus Handicap Inventory (THI) score of 38 or greater.
Subjects of child-bearing potential using an appropriate form of birth control acceptable to the research team and with a negative urine pregnancy test or undergone sterilization procedure.
Able to give informed consent.
Available for once daily therapy, during working hours, Mon.-Fri.
English-speaking.

Who cannot join

Patients experiencing tinnitus related to cochlear implantation, retrocochlear lesion, or other known anatomic/structural lesions of the ear and temporal bone.
Patients with hyperacusis or misophonia (hyper-sensitivity to loud noises).
History of seizures, history of loss of consciousness requiring medical care, any other CNS pathology that increases a subject's risk for treatment with rTMS.
Patients with cardiac pacemakers, intracardiac lines, implanted medication pumps, implanted electrodes in the brain, other intracranial metal objects with the exception of dental fillings, or any other contraindication for MRI scan.
Any contraindication for receiving FDG PET, as determined by established clinical criteria.
Patients with an acute or chronic unstable medical condition which, in the opinion of the investigator, would require stabilization prior to initiation of magnetic stimulation.

Show all 25Show fewer

Patients with any active ear disease that, in the opinion of the PI, needs to be further evaluated.
Patients with symptoms of depression as evidenced by a score of 14 or greater on the Beck Depression Inventory or, in the opinion of the psychiatric sub-investigator demonstrates active mood symptoms that meet DSM-IV-TR criteria for Major Depressive Disorder.
Any psychiatric co-morbidity that, in the opinion of the psychiatric sub-investigator, may complicate the interpretation of study results.
Pregnancy
Currently breast-feeding
Previous treatment with rTMS
Patients with tinnitus related to Workman's Compensation claim or litigation-related event.
Patients with a history of diabetes.
Fasting glucose > 150mg/Dl.
Patients taking any medication(s), in the opinion of the investigator, that is(are) deemed to be etiologically related to the development of tinnitus.
Unable to elicit a motor threshold with rTMS.
A Mini-Mental Status Exam score less than 27.
Untreated or newly diagnosed hypertension, (systolic blood pressures above 140 mm or diastolic pressure above 90 mm).
Patients with a history of claustrophobia.
Inability to lay flat for 2 hours.
Active alcohol and/or drug dependence or history of alcohol and/or ETOH dependence within the last year.
Any medical condition that, in the opinion of the investigators, confounds study results or places the subject at greater risk.
Unable to provide informed consent.
Any exclusions from radiology screening for MRI or PET scanning.

Trial locations and contacts

1 site in 1 country.

United States1 site

Washington University Medical Center
St Louis, Missouri, 63110

Other trials in United States

About this study

The goal of this trial to see if repetitive transcranial magnetic stimulation (rTMS) to the hearing area of the brain can lessen the perception of tinnitus. rTMS uses a strong magnet and when placed against the scalp generates a small electrical field within the brain. Depending on the frequency of the stimulation, this electrical field can either decrease or increase the electrical excitability of the brain. In this study, low-frequency stimulation will be used, which is thought to decrease nerve activity. It is this electrical excitability of the brain that is thought to be responsible for tinnitus.

The hypothesis of this study is that rTMS can decrease the perception of tinnitus.

Read the detailed description

This will be a cross-over randomized trial. The order of the treatments received will be randomly selected and the participant will not be told which treatment they are receiving. Subjects will fall into one of the four treatment groups described below:

2 weeks of active rTMS treatment followed by washout and then by 2 weeks sham
2 weeks of sham followed by washout and then 2 weeks of active rTMS treatment
4 weeks of active rTMS treatment followed by washout and then 4 weeks of sham
4 weeks of sham followed by washout and then 4 weeks of active rTMS treatment

For the washout period between the two interventions, we will plan a minimum of 2 weeks to avoid the problem of carryover effects. Prior to starting the next intervention after the washout period, we will re-assess subject's tinnitus severity. To ensure no carryover effect, the washout period will be extended for those subjects whose tinnitus severity, as defined by the THI, is more than 20 points different than their baseline THI score.

Conditions: Subjective Tinnitus
Being tested: rTMS
Keywords: tinnitus, subjective tinnitus, therapy, repetitive transcranial magnetic stimulation, clinical trial
Medical subject headings: Tinnitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

rTMSDevice
Also called Neuronetics 2100 device
Stimulation Settings:
Frequency -- 1Hz on 330 sec (5 min 30 sec.) per train for the first 5 trains with the last train 350 sec. (5 min. 50 sec.) in duration Off -- 90 sec (1 min. 30 sec.) Intensity -- 110% of motor threshold Duration -- 42½ minutes (total 2000 pulses in 6 trains)

Study groups in NCT00567892
Study group	Role	What they receive
1. rTMS	Experimental	Stimulation Settings: Frequency -- 1Hz on 330 sec (5 min 30 sec.) per train for the first 5 trains with the last train 350 sec. (5 min. 50 sec.) in duration Off -- 90 sec (1 min. 30 sec.) Intensity -- 110% of motor threshold Duration -- 42½ minutes (total 2000 pulses in 6 trains) Receives: Device: rTMS
2. Sham rTMS	Sham comparator	Sham rTMS appears identical to and mimics sounds and sensations of active magnet. Receives: Device: rTMS

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in THI (Tinnitus Handicap Inventory)
Tinnitus Handicap Inventory (THI) is a measure of bother from tinnitus. THI is measured as a score in a scale ranging from 0=No bother to 100=Extremely Bothered. THI score post active rTMS treatment minus THI score pre active rTMS treatment will provide the change in THI score due to active treatment. THI score post rTMS sham minus THI score pre rTMS sham will provide change in THI due to sham. The difference of THI change due to active treatment minus THI change due to sham will provide the THI change that is our primary outcome measure.
Measured: baseline at the start of each treatment period, end of each treatment period (2 or 4 weeks)

Secondary outcomes (1)

Perceived Global Impression of Change (PGIC: Number of Participants With Perceived Global Impression of Change (PGIC) of 1 or Greater
PGIC is a 7 point scale ranging from -3 to +3,with 0 meaning no change,negative values reporting worsening of symptoms(Tinnitus), and values of +1 or above reporting perceived improvement of Tinnitus.
PGIC score post active rTMS treatment treatment will provide subject's impression of change in tinnitue due to active treatment.PGIC score post rTMS sham will provide subject's impression of change in tinnitus due to sham. Number of subjects with scores of 1 or above are recorded to perceive improvement due to treatment of the corresponding study arm.
Measured: End of each treatment period (2 or 4 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2008Jun 2011

First posted5 Dec 2007 (estimated)
Study startJan 2008
Primary completionJun 2011
Study completionJun 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Subjective TinnitusStudies of the same condition, open and under way.
More trials run by Washington University School of MedicineThe sponsor's other registered studies.
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: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 55 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00567892
Sponsor's protocol ID: 07-0689
Other IDs: R01DC009095
Acronym: CTRWU
Status last verified: Oct 2018
First submitted: 3 Dec 2007
Last updated: 16 Nov 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Piccirillo JF, Garcia KS, Nicklaus J, Pierce K, Burton H, Vlassenko AG, Mintun M, Duddy D, Kallogjeri D, Spitznagel EL Jr. Low-frequency repetitive transcranial magnetic stimulation to the temporoparietal junction for tinnitus. Arch Otolaryngol Head Neck Surg. 2011 Mar;137(3):221-8. doi: 10.1001/archoto.2011.3.
PubMed 21422304
Pierce KJ, Kallogjeri D, Piccirillo JF, Garcia KS, Nicklaus JE, Burton H. Effects of severe bothersome tinnitus on cognitive function measured with standardized tests. J Clin Exp Neuropsychol. 2012;34(2):126-34. doi: 10.1080/13803395.2011.623120. Epub 2011 Dec 14.
PubMed 22168528
Burton H, Wineland A, Bhattacharya M, Nicklaus J, Garcia KS, Piccirillo JF. Altered networks in bothersome tinnitus: a functional connectivity study. BMC Neurosci. 2012 Jan 4;13:3. doi: 10.1186/1471-2202-13-3.
PubMed 22217183
Piccirillo JF, Kallogjeri D, Nicklaus J, Wineland A, Spitznagel EL Jr, Vlassenko AG, Benzinger T, Mathews J, Garcia KS. Low-frequency repetitive transcranial magnetic stimulation to the temporoparietal junction for tinnitus: four-week stimulation trial. JAMA Otolaryngol Head Neck Surg. 2013 Apr;139(4):388-95. doi: 10.1001/jamaoto.2013.233.
PubMed 23599075

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Acute Nicotine Gum and Auditory Brain Responses in Adults With Chronic Tinnitus
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Tinnitus, Subjective
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Efficacy Analysis of Transcutaneous Auricular Vagus Nerve Stimulation Combined With Tailor-Made Notched Music Therapy in the Treatment of Chronic Subjective Tinnitus
Chronic Subjective Tinnitus
Recruiting
Non-Invasive Neurofeedback Training to Alleviate Tinnitus Distress
Tinnitus Aggravated, Tinnitus
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COMPARISON OF MANUAL THERAPY, TINNITUS RETRAINING THERAPY
Somatosensory Tinnitus, Subjektif tınnitus

All Subjective Tinnitus trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Collaborative Tinnitus Research at Washington University
ClinicalTrials.gov ID: NCT00567892
Acronym / sponsor ID: CTRWU / 07-0689
Conditions: Subjective Tinnitus
Keywords: tinnitus, subjective tinnitus, therapy, repetitive transcranial magnetic stimulation, clinical trial
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 55 participants (actual)
Lead sponsor: Washington University School of MedicineUniversity, hospital or other
Collaborators: National Institute on Deafness and Other Communication Disorders (NIDCD)
Study start: Jan 2008
Primary completion: Jun 2011 (actual)
Study completion: Jun 2011 (actual)
First posted: 5 Dec 2007 (estimated)
Results: Posted 27 Aug 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The hypothesis of this study is that rTMS can decrease the perception of tinnitus.

Detailed description

2 weeks of active rTMS treatment followed by washout and then by 2 weeks sham
2 weeks of sham followed by washout and then 2 weeks of active rTMS treatment
4 weeks of active rTMS treatment followed by washout and then 4 weeks of sham
4 weeks of sham followed by washout and then 4 weeks of active rTMS treatment

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
1. rTMS	Experimental	Device: rTMSStimulation Settings: Frequency -- 1Hz on 330 sec (5 min 30 sec.) per train for the first 5 trains with the last train 350 sec. (5 min. 50 sec.) in duration Off -- 90 sec (1 min. 30 sec.) Intensity -- 110% of motor threshold Duration -- 42½ minutes (total 2000 pulses in 6 trains)
2. Sham rTMS	Sham comparator	Device: rTMSSham rTMS appears identical to and mimics sounds and sensations of active magnet.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Men and women between the ages of 18 and 60 years.
Subjective, unilateral or bilateral, non-pulsatile tinnitus of 6 month's duration or greater.
Tinnitus Handicap Inventory (THI) score of 38 or greater.
Subjects of child-bearing potential using an appropriate form of birth control acceptable to the research team and with a negative urine pregnancy test or undergone sterilization procedure.
Able to give informed consent.

Key exclusion criteria (25 listed)

Patients experiencing tinnitus related to cochlear implantation, retrocochlear lesion, or other known anatomic/structural lesions of the ear and temporal bone.
Patients with hyperacusis or misophonia (hyper-sensitivity to loud noises).
History of seizures, history of loss of consciousness requiring medical care, any other CNS pathology that increases a subject's risk for treatment with rTMS.
Patients with cardiac pacemakers, intracardiac lines, implanted medication pumps, implanted electrodes in the brain, other intracranial metal objects with the exception of dental fillings, or any other contraindication for MRI scan.
Any contraindication for receiving FDG PET, as determined by established clinical criteria.

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
rTMSAlso: Neuronetics 2100 deviceStimulation Settings: Frequency -- 1Hz on 330 sec (5 min 30 sec.) per train for the first 5 trains with the last train 350 sec. (5 min. 50 sec.) in duration Off -- 90 sec (1 min. 30 sec.) Intensity -- 110% of motor threshold Duration -- 42½ minutes (total 2000 pulses in 6 trains)	Device	1. rTMS, 2. Sham rTMS

Primary outcome

Change in THI (Tinnitus Handicap Inventory)
Time frame: baseline at the start of each treatment period, end of each treatment period (2 or 4 weeks)
Tinnitus Handicap Inventory (THI) is a measure of bother from tinnitus. THI is measured as a score in a scale ranging from 0=No bother to 100=Extremely Bothered. THI score post active rTMS treatment minus THI score pre active rTMS treatment will provide the change in THI score due to active treatment. THI score post rTMS sham minus THI score pre rTMS sham will provide change in THI due to sham. The difference of THI change due to active treatment minus THI change due to sham will provide the THI change that is our primary outcome measure.

1 secondary outcome

Perceived Global Impression of Change (PGIC: Number of Participants With Perceived Global Impression of Change (PGIC) of 1 or Greater
Time frame: End of each treatment period (2 or 4 weeks)

Results and safety

Results posted to the registry on 27 Aug 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Active Then Sham rTMS Treatment (2 Weeks)	7	7
Sham Then Active rTMS Treatment (2 Weeks)	7	7
Active Then Sham rTMS Treatment (4 Weeks)	10	9
Sham Then Active rTMS Treatment (4 Weeks)	10	6

Primary outcome: Change in THI (Tinnitus Handicap Inventory)

Time frame: baseline at the start of each treatment period, end of each treatment period (2 or 4 weeks). Median (95% Confidence Interval). Unit: units on a scale

Measure	2-weeks rTMS Active Treatment n = 14	2-Weeks Sham rTMS Treatment n = 14	4-weeks rTMS Active Treatment n = 13	4-weeks rTMS Sham Treatment n = 13
Value	-5 (-14 to 0)	-6 (-12 to -2)	-10 (-12 to 3)	-6 (-12 to 4)

2-weeks rTMS Active Treatment vs 2-Weeks Sham rTMS Treatment: Median Difference (Net): 0 (95% CI -6 to 4), p = 0.944, Wilcoxon signed rank test
4-weeks rTMS Active Treatment vs 4-weeks rTMS Sham Treatment: Median Difference (Net): -4 (95% CI -9 to 10), p = 0.674, Wilcoxon signed rank test

Population analysed: Study participant that successfully completed both study parts active rTMS treatment and sham rTMS treatment were included in analysis.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Up to 6 months.Minimum of 10 weeks in 2wk treatment, or 14 weeks in 4 week treatment.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
2 Weeks Treatment	0 of 14 (0%)	7 of 14 (50%)	Not reported
Four Week Treatment	0 of 20 (0%)	3 of 20 (15%)	Not reported

Limitations and caveats (from the sponsor): Excluding subjects with Beck Depression Index of above 14 we treated an exclusive group of the Very bothered tinnitus patients, which may not be representative of the tinnitus population as a whole.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21422304Piccirillo JF, Garcia KS, Nicklaus J, Pierce K, Burton H, Vlassenko AG, Mintun M, Duddy D, Kallogjeri D, Spitznagel EL Jr. Low-frequency repetitive transcranial magnetic stimulation to the temporoparietal junction for tinnitus. Arch Otolaryngol Head Neck Surg. 2011 Mar;137(3):221-8. doi: 10.1001/archoto.2011.3.
Results publication: PubMed 22168528Pierce KJ, Kallogjeri D, Piccirillo JF, Garcia KS, Nicklaus JE, Burton H. Effects of severe bothersome tinnitus on cognitive function measured with standardized tests. J Clin Exp Neuropsychol. 2012;34(2):126-34. doi: 10.1080/13803395.2011.623120. Epub 2011 Dec 14.
Results publication: PubMed 22217183Burton H, Wineland A, Bhattacharya M, Nicklaus J, Garcia KS, Piccirillo JF. Altered networks in bothersome tinnitus: a functional connectivity study. BMC Neurosci. 2012 Jan 4;13:3. doi: 10.1186/1471-2202-13-3.
Derived from this study: PubMed 23599075Piccirillo JF, Kallogjeri D, Nicklaus J, Wineland A, Spitznagel EL Jr, Vlassenko AG, Benzinger T, Mathews J, Garcia KS. Low-frequency repetitive transcranial magnetic stimulation to the temporoparietal junction for tinnitus: four-week stimulation trial. JAMA Otolaryngol Head Neck Surg. 2013 Apr;139(4):388-95. doi: 10.1001/jamaoto.2013.233.

Related trials for Subjective Tinnitus

Not yet recruitingPhase 1/2
Acute Nicotine Gum and Auditory Brain Responses in Adults With Chronic Tinnitus
Tinnitus, Chronic Subjective Tinnitus
Not yet recruiting
Advanced Neurofeedback for Tinnitus
Tinnitus, Subjective
Not yet recruiting
Efficacy Analysis of Transcutaneous Auricular Vagus Nerve Stimulation Combined With Tailor-Made Notched Music Therapy in the Treatment of Chronic Subjective Tinnitus
Chronic Subjective Tinnitus
Recruiting
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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.

Jay F Piccirillo, MD, CPI principal investigator

Washington University School of Medicine

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 rTMS in people with Subjective Tinnitus, run by Washington University School of Medicine at 1 site in United States.

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 7 inclusion and 25 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 16 Nov 2018. 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 United States. 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?

Yes. Results are posted in the registry (first posted 27 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change in THI (Tinnitus Handicap Inventory) (time frame: baseline at the start of each treatment period, end of each treatment period (2 or 4 weeks)). 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 NCT00567892, which also lists 4 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 16 Nov 2018.