Effect of rTMS on Resting State Brain Activity in Tinnitus

Tracking Information
First Submitted Date ICMJE	June 19, 2009
First Posted Date ICMJE	June 23, 2009
Last Update Posted Date	October 4, 2017
Study Start Date ICMJE	January 2009
Estimated Primary Completion Date	September 2020 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 24, 2012)	Change in tinnitus perception, as measured over time using a subjective visual analog rating scale [ Time Frame: At subject enrollment, before and after each active or sham rTMS session, inbetween active and sham treatments, and 2 months following the end of treatment. ]
Original Primary Outcome Measures ICMJE; (submitted: June 22, 2009)	Change in tinnitus perception, as measured over time using a subjective visual analog rating scale [ Time Frame: At subject enrollment, before and after each active or sham rTMS session, and via daily tinnitus log lasting for up to 6 months following rTMS therapy ]; Change in metabolic activity from pre-treatment to post-treatment PET-CT brain scans for the brain regions targeted with rTMS therapy, calculated as the difference of the asymmetry ratios for each. [ Time Frame: PET-CT scans obtained before and immediately following the first week of rTMS therapy (sham and active) ]
Change History	Complete list of historical versions of study NCT00926237 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 24, 2012)	Change in Beck's Depression Inventory (BDI) [ Time Frame: BDI data obtained at the beginning and the end of each week of rTMS therapy ]; Change in Tinnitus Handicap Inventory (THI) [ Time Frame: THI data obtained at the beginning and the end of each week of rTMS treatment and at 2 month follow up ]; EEG measures of spectral power and coherence [ Time Frame: EEG recordings will be made at baseline, the end of each treatment week, and at 2 month follow-up ]
Original Secondary Outcome Measures ICMJE; (submitted: June 22, 2009)	Change in hearing threshold [ Time Frame: Audiology evaluations obtained before and after the initial two weeks of rTMS therapy ]; Change in psychomotor vigilance testing (PVT) [ Time Frame: PVT data obtained at the beginning and the end of each week of rTMS therapy ]; Change in Beck's Depression Inventory (BDI) [ Time Frame: BDI data obtained at the beginning and the end of each week of rTMS therapy ]; Change in Tinnitus Severity Index (TSI) [ Time Frame: TSI data obtained at the beginning and the end of each week of rTMS therapy ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Effect of rTMS on Resting State Brain Activity in Tinnitus
Official Title ICMJE	Effect of rTMS on Resting State Brain Activity in Tinnitus
Brief Summary	One out of every five people experiences tinnitus (a ringing, buzzing, or roaring sound in the ear) ranging from mild to severe impairment. To date, there are no effective therapies available that have been shown to decrease tinnitus loudness. The purpose of this study is to develop a new treatment option for tinnitus using a technique called Repetitive Transcranial Magnetic Stimulation (rTMS), which will hopefully prove to be an effective means of alleviating or reducing the symptoms of tinnitus.
Detailed Description	This research is being conducted at the University of Arkansas for Medical Sciences (UAMS). Up to 60 subjects, including males and females ages 19-89 years old and of all races, and with tinnitus severe enough to seek medical attention, will be enrolled in this study. All participants will be evaluated or medically reviewed by the study physician, Dr. Dornhoffer of the Hearing and Balance Clinic at UAMS, including a modified physical examination and hearing tests, prior to beginning therapy with rTMS in order to rule out any medically treatable causes of tinnitus. An MRI scan of the head may or may not be required, depending upon the results of this evaluation, in order to rule out specific middle ear pathologies. This study will require participation in at least three weeks (4 weekdays per week) of rTMS sessions, including two active weeks and a sham (or placebo) week. There will be a three week washout period following each treatment week. At the completion of the three treatment weeks, subjects who have noticed an improvement in their tinnitus will have the option of participating in a maintenance rTMS program providing up to 8 additional weeks of treatment.
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Tinnitus
Intervention ICMJE	Device: Repetitive Transcranial Magnetic Stimulation (rTMS) - ACTIVE Active rTMS will be targeted according to the following decision tree: 1) to auditory cortex in the superior temporal gyrus opposite the ear with loudest tinnitus; 2) to the same region in the left temporal lobe. Active stimulation will be delivered at 110% of motor threshold (MT) at a frequency of 1 or 10 Hz for a total of 1800 magnetic pulses per session (and a total of 4 sessions per week of active rTMS therapy).; Device: Repetitive Transcranial Magnetic Stimulation (rTMS) - SHAM Sham rTMS will be targeted using a commercially available sham coil and delivered to the same site within the temporal lobe as active rTMS and in a manner identical to that for active rTMS except that scalp electrodes are used to stimulate the temporalis muscle electrically during sham stimulation to replicate the feel of active TMS.
Study Arms	Sham Comparator: Active/Sham Protocol All subjects complete the initial three weeks of rTMS sessions, which include 8 active sessions and 4 sham sessions. Subjects receive sham stimulation first to prevent carry forward effects of active treatment. Active and sham weeks are separated for each subject by an interval of no less than 21 days. Interventions: Device: Repetitive Transcranial Magnetic Stimulation (rTMS) - ACTIVE Device: Repetitive Transcranial Magnetic Stimulation (rTMS) - SHAM; Active Comparator: Maintenance rTMS Subjects who respond to either week of active rTMS have the option of participating in a maintenance rTMS program involving up to 8 additional sessions of therapy, each consisting of 3 days of rTMS treatment. Maintenance sessions will be scheduled with three weeks separating each treatment. Intervention: Device: Repetitive Transcranial Magnetic Stimulation (rTMS) - ACTIVE
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: April 24, 2012)	60
Original Estimated Enrollment ICMJE; (submitted: June 22, 2009)	10
Estimated Study Completion Date	September 2020
Estimated Primary Completion Date	September 2020 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Diagnosis of tinnitus established through a history and physical exam or review or records performed by the study physician; Subjects 19-89 years of age; Tinnitus present for at least 6 months and severe enough to seek medical attention; Subjects taking SSRI's (a class of anti-depressant medications)and benzodiazepines (a class of anti-anxiety medications) for depression or anxiety related to tinnitus must be stable on their current dose for at least 3 months and must not alter their dose or medication during their involvement with this study; Subjects must agree to avoid consuming alcohol within 72 hours of each rTMS session; Female subjects of childbearing potential must demonstrate a negative pregnancy test during their initial clinic visit and must agree to use effective contraception during their participation in this study; Subjects must sign an informed consent and agree to comply with study and follow-up procedures, including completion of all necessary questionnaires and testing, as well as, being video-recorded for safety purposes during rTMS sessions; Subjects must speak and comprehend English adequately to understand and complete any study-related instructions and questionnaires Exclusion Criteria: Subjects or any of their 1st-degree relatives must not have been diagnosed with epilepsy; Subjects must not have a history of seizure disorder or migraines; Subjects must not have any history of a brain aneurysm, stroke, previous cranial neurosurgery, acoustic neuroma, glomus tumor, active Menniere's Disease, profound hearing loss (greater than 90 dB at 4000 Hz), or any major neurological or psychiatric disorders (excluding depression or anxiety related to tinnitus); Subjects must not have any history of a head injury that resulted in a loss of consciousness for more than 10 minutes; Subjects must not have any metal implants or devices in the head or neck or a pacemaker.; Subjects must not have severe claustrophobia if they are to have an MRI. Significant abnormalities must not be present on acquired or existing CT or MRI image of the head.; Subjects must not be pregnant or refuse to utilize effective contraception during their participation in this study; Subjects must not have any history of Bipolar Disease
Sex/Gender	Sexes Eligible for Study: All
Ages	19 Years to 89 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Mark S Mennemeier, PhD msmennemeier@uams.edu Contact: Helen Hayes 501-686-5373 hrhayes@uams.edu
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00926237
Other Study ID Numbers ICMJE	109033
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	University of Arkansas
Study Sponsor ICMJE	University of Arkansas
Collaborators ICMJE	National Institutes of Health (NIH)
Investigators ICMJE	Principal Investigator: Mark Mennemeier, PhD UAMS Department of Neurosciences
PRS Account	University of Arkansas
Verification Date	October 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP