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The purpose of this research study is to determine if a medication along with a computer program designed to improve memory and other mental processes can help people like yourself with tinnitus. The medication that will be investigated, d-cycloserine, was developed as an antibiotic. However, more recently, research in other studies has shown that this medication may enhance learning and memory. The investigators would like to determine if computer programs designed to improve memory and attention are enhanced by this medication. In addition, the investigators hope to learn if the use of these programs can help participants with their tinnitus as well as their ability to remember and focus. All research participants will receive therapy with a computer-based program designed to improve memory and attention. Half of participants will also receive d-cycloserine while the other half of participants will receive placebo. The placebo is a sugar pill without active medication.
Tinnitus is the perception of a "ringing or hissing" sound in the absence of an acoustic stimulus affecting more than 40 million people in the United States. While the exact etiology of chronic bothersome tinnitus is unknown, current evidence based on numerous studies and neuroimaging results suggests chronic bothersome tinnitus involves the central nervous system with abnormalities in neural networks including attention and emotional networks. These neuroplastic changes in multiple neural networks may offer targets in the treatment of chronic bothersome tinnitus.
The Brain Fitness Program® (Posit Science Corporation, San Francisco, California) is a cognitive rehabilitation program that has been used in the treatment of schizophrenia and geriatric populations, and has been shown to have favorable results by reorganizing aberrant neural networks. Preliminary results from our team have shown improvements in tinnitus severity and cognitive functioning for participants with chronic bothersome tinnitus using this cognitive rehabilitation program.
Recent studies in numerous disorders have shown d-cycloserine (DCS) augments learning therapy programs by enhancing neuroplasticity. In addition, the adjuvant use of DCS with learning therapies has been found to accelerate symptom reduction decreasing the time-burden needed for learning therapies. Based on the belief that chronic bothersome tinnitus involves changes in malleable neural networks that can be targets of therapy and that DCS enhances neuroplasticity, the investigators hypothesize that adjuvant DCS with cognitive rehabilitation treatment may improve tinnitus severity and the cognitive deficits associated with chronic bothersome tinnitus.
This randomized-controlled trial will use an abbreviated cognitive rehabilitation program given for 5 weeks with DCS or placebo to evaluate the impact of a neuroplasticity-sensitizing drug on tinnitus symptom severity and cognitive performance among patients with chronic bothersome tinnitus. A positive result on this study will have numerous implications, including offering a new treatment option for chronic bothersome tinnitus with few known side effects and limited time commitment or cost.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| d-cycloserine | Active Comparator | d-cycloserine 250 mg two days per week one hour prior to(cognitive training) |
|
| Placebo | Placebo Comparator | Placebo pill two days per week 1 hour prior to cognitive training |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cognitive Training | Behavioral | 250 mg d-cycloserine or placebo taken orally one hour before Brain Fitness Program |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in Tinnitus Handicap Inventory (THI) | We will measure THI before and after treatment. Primary efficacy is defined by a decrease of 17 points on their THI from baseline. | Baseline and 5 weeks later |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Neurocognitive assessment score | We will measure PASAT, Stroop, and a newly designed neurocognitive computer based test at the patient's baseline visit and final visit. These assessments are done as patients with tinnitus frequently report cognitive difficulties in attention and memory. One aim of this study is to target these cognitive difficulties. Improvements in memory and attention will be assessed using these neurocognitive tests. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jay F Piccirillo, MD | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21309114 | Background | Choi DC, Rothbaum BO, Gerardi M, Ressler KJ. Pharmacological enhancement of behavioral therapy: focus on posttraumatic stress disorder. Curr Top Behav Neurosci. 2010;2:279-99. doi: 10.1007/7854_2009_10. | |
| 19448187 | Background | Fisher M, Holland C, Merzenich MM, Vinogradov S. Using neuroplasticity-based auditory training to improve verbal memory in schizophrenia. Am J Psychiatry. 2009 Jul;166(7):805-11. doi: 10.1176/appi.ajp.2009.08050757. Epub 2009 May 15. |
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| ID | Term |
|---|---|
| D014012 | Tinnitus |
| ID | Term |
|---|---|
| D006311 | Hearing Disorders |
| D004427 | Ear Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D012678 | Sensation Disorders |
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| ID | Term |
|---|---|
| D000091942 | Cognitive Training |
| ID | Term |
|---|---|
| D000066530 | Neurological Rehabilitation |
| D012046 | Rehabilitation |
| D000359 | Aftercare |
| D003266 | Continuity of Patient Care |
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| Baseline and 5 weeks later |
| 20599140 | Background | Ganasen KA, Ipser JC, Stein DJ. Augmentation of cognitive behavioral therapy with pharmacotherapy. Psychiatr Clin North Am. 2010 Sep;33(3):687-99. doi: 10.1016/j.psc.2010.04.008. |
| 16411806 | Background | Henry JA, Dennis KC, Schechter MA. General review of tinnitus: prevalence, mechanisms, effects, and management. J Speech Lang Hear Res. 2005 Oct;48(5):1204-35. doi: 10.1044/1092-4388(2005/084). |
| 10755809 | Background | Kaltenbach JA. Neurophysiologic mechanisms of tinnitus. J Am Acad Audiol. 2000 Mar;11(3):125-37. |
| 8442938 | Background | Lenarz T, Schreiner C, Snyder RL, Ernst A. Neural mechanisms of tinnitus. Eur Arch Otorhinolaryngol. 1993;249(8):441-6. doi: 10.1007/BF00168851. |
| 12239260 | Background | Lockwood AH, Salvi RJ, Burkard RF. Tinnitus. N Engl J Med. 2002 Sep 19;347(12):904-10. doi: 10.1056/NEJMra013395. No abstract available. |
| 10803913 | Background | Lockwood AH, Salvi RJ, Burkard RF, Galantowicz PJ, Coad ML, Wack DS. Neuroanatomy of tinnitus. Scand Audiol Suppl. 1999;51:47-52. |
| 20670725 | Background | Shargorodsky J, Curhan GC, Farwell WR. Prevalence and characteristics of tinnitus among US adults. Am J Med. 2010 Aug;123(8):711-8. doi: 10.1016/j.amjmed.2010.02.015. |
| 21377691 | Background | Siegmund A, Golfels F, Finck C, Halisch A, Rath D, Plag J, Strohle A. D-cycloserine does not improve but might slightly speed up the outcome of in-vivo exposure therapy in patients with severe agoraphobia and panic disorder in a randomized double blind clinical trial. J Psychiatr Res. 2011 Aug;45(8):1042-7. doi: 10.1016/j.jpsychires.2011.01.020. Epub 2011 Mar 5. |
| 19220558 | Background | Smith GE, Housen P, Yaffe K, Ruff R, Kennison RF, Mahncke HW, Zelinski EM. A cognitive training program based on principles of brain plasticity: results from the Improvement in Memory with Plasticity-based Adaptive Cognitive Training (IMPACT) study. J Am Geriatr Soc. 2009 Apr;57(4):594-603. doi: 10.1111/j.1532-5415.2008.02167.x. Epub 2009 Feb 9. |
| 25356570 | Derived | Krings JG, Wineland A, Kallogjeri D, Rodebaugh TL, Nicklaus J, Lenze EJ, Piccirillo JF. A novel treatment for tinnitus and tinnitus-related cognitive difficulties using computer-based cognitive training and D-cycloserine. JAMA Otolaryngol Head Neck Surg. 2015 Jan;141(1):18-26. doi: 10.1001/jamaoto.2014.2669. |
| D009461 |
| Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D005791 |
| Patient Care |
| D013812 | Therapeutics |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |