Clinical Trial to Evaluate the Safety and Efficacy of MeRT Treatment in Persistent Post-Concussive Symptoms (PPCS) (MeRT-TBI-005)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02990793|
Recruitment Status : Suspended (Preparing for Phase II.)
First Posted : December 13, 2016
Last Update Posted : November 20, 2019
Uniformed Services University of the Health Sciences
U.S. Special Operations Command
Henry M. Jackson Foundation for the Advancement of Military Medicine
Information provided by (Responsible Party):
No Study Results Posted on ClinicalTrials.gov for this Study
|Recruitment Status :||Suspended|
|Estimated Primary Completion Date :||January 2021|
|Estimated Study Completion Date :||January 2021|
Abelson JL, Curtis GC, Sagher O, Albucher RC, Harrigan M, Taylor SF, Martis B, Giordani B. Deep brain stimulation for refractory obsessive-compulsive disorder. Biol Psychiatry. 2005 Mar 1;57(5):510-6.
Achard S, Delon-Martin C, Vértes PE, Renard F, Schenck M, Schneider F, Heinrich C, Kremer S, Bullmore ET. Hubs of brain functional networks are radically reorganized in comatose patients. Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20608-13. doi: 10.1073/pnas.1208933109. Epub 2012 Nov 26.
ACRM: Mild Traumatic Brain Injury Committee. (1993). Definition of mild traumatic brain injury. J Head Trauma Rehabil, 8, 86-87.
American Psychiatric Association Task Force on DSM-IV. (2000). Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed. Washington, DC: American Psychiatric Association.
Arciniegas DB, Silver JM. Regarding the search for a unified definition of mild traumatic brain injury. Brain Inj. 2001 Jul;15(7):649-52.
Bae EH, Schrader LM, Machii K, Alonso-Alonso M, Riviello JJ Jr, Pascual-Leone A, Rotenberg A. Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature. Epilepsy Behav. 2007 Jun;10(4):521-8. Epub 2007 May 9. Review.
Blyth BJ, Bazarian JJ. Traumatic alterations in consciousness: traumatic brain injury. Emerg Med Clin North Am. 2010 Aug;28(3):571-94. doi: 10.1016/j.emc.2010.03.003. Review.
Bonita JD, Ambolode LC 2nd, Rosenberg BM, Cellucci CJ, Watanabe TA, Rapp PE, Albano AM. Time domain measures of inter-channel EEG correlations: a comparison of linear, nonparametric and nonlinear measures. Cogn Neurodyn. 2014 Feb;8(1):1-15. doi: 10.1007/s11571-013-9267-8. Epub 2013 Sep 4. Review.
Carroll LJ, Cassidy JD, Holm L, Kraus J, Coronado VG; WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. Methodological issues and research recommendations for mild traumatic brain injury: the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med. 2004 Feb;(43 Suppl):113-25.
Castellanos NP, Bajo R, Cuesta P, Villacorta-Atienza JA, Paúl N, Garcia-Prieto J, Del-Pozo F, Maestú F. Alteration and reorganization of functional networks: a new perspective in brain injury study. Front Hum Neurosci. 2011 Sep 21;5:90. doi: 10.3389/fnhum.2011.00090. eCollection 2011.
Castellanos NP, Paúl N, Ordóñez VE, Demuynck O, Bajo R, Campo P, Bilbao A, Ortiz T, del-Pozo F, Maestú F. Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury. Brain. 2010 Aug;133(Pt 8):2365-81. doi: 10.1093/brain/awq174.
Chen YH, DeMets DL, Lan KK. Increasing the sample size when the unblinded interim result is promising. Stat Med. 2004 Apr 15;23(7):1023-38.
Comerchero MD, Polich J. P3a and P3b from typical auditory and visual stimuli. Clin Neurophysiol. 1999 Jan;110(1):24-30.
CONSORT Group. (2010). CONSORT 2010. Retrieved January 13, 2016, from CONSORT Transparent Reporting of Trials: http://www.consort-statement.org/consort-2010
De Beaumont L, Mongeon D, Tremblay S, Messier J, Prince F, Leclerc S, Lassonde M, Théoret H. Persistent motor system abnormalities in formerly concussed athletes. J Athl Train. 2011 May-Jun;46(3):234-40.
Dhamne SC, Kothare RS, Yu C, Hsieh TH, Anastasio EM, Oberman L, Pascual-Leone A, Rotenberg A. A measure of acoustic noise generated from transcranial magnetic stimulation coils. Brain Stimul. 2014 May-Jun;7(3):432-4. doi: 10.1016/j.brs.2014.01.056. Epub 2014 Jan 29.
Di Stefano G, Bachevalier J, Levin HS, Song JX, Scheibel RS, Fletcher JM. Volume of focal brain lesions and hippocampal formation in relation to memory function after closed head injury in children. J Neurol Neurosurg Psychiatry. 2000 Aug;69(2):210-6.
Dupont WD, Plummer WD Jr. Power and sample size calculations. A review and computer program. Control Clin Trials. 1990 Apr;11(2):116-28.
Dupont, W. D., & Plummer, W. D. (1997). Power and Sample Size software. Controlled Clinical Trials, 18, 274.
Dupont WD, Plummer WD Jr. Power and sample size calculations for studies involving linear regression. Control Clin Trials. 1998 Dec;19(6):589-601.
Eckberg, D. L. (2004). Correlations among heart rate variability components and autonomic mechanisms. In M. Malik, & J. A. Camm (Eds.), Dynamic Electrocardiology (pp. 31-39). Elmsford, NY, US: Blackwell/Futura.
García-González MA, Fernández-Chimeno M, Ferrer J, Escorihuela RM, Parrado E, Capdevila L, Benítez A, Angulo R, Rodríguez FA, Iglesias X, Bescós R, Marina M, Padullés JM, Ramos-Castro J. New indices for quantification of the power spectrum of heart rate variability time series without the need of any frequency band definition. Physiol Meas. 2011 Aug;32(8):995-1009. doi: 10.1088/0967-3334/32/8/001. Epub 2011 Jun 7.
Geuze E, Vermetten E, Bremner JD. MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Mol Psychiatry. 2005 Feb;10(2):160-84. Review.
Gevins A, Cutillo B. Spatiotemporal dynamics of component processes in human working memory. Electroencephalogr Clin Neurophysiol. 1993 Sep;87(3):128-43.
Gondusky JS, Reiter MP. Protecting military convoys in Iraq: an examination of battle injuries sustained by a mechanized battalion during Operation Iraqi Freedom II. Mil Med. 2005 Jun;170(6):546-9.
Gordon WA, Haddad L, Brown M, Hibbard MR, Sliwinski M. The sensitivity and specificity of self-reported symptoms in individuals with traumatic brain injury. Brain Inj. 2000 Jan;14(1):21-33.
Hardmeier M, Hatz F, Bousleiman H, Schindler C, Stam CJ, Fuhr P. Reproducibility of functional connectivity and graph measures based on the phase lag index (PLI) and weighted phase lag index (wPLI) derived from high resolution EEG. PLoS One. 2014 Oct 6;9(10):e108648. doi: 10.1371/journal.pone.0108648. eCollection 2014.
Hoge CW, Goldberg HM, Castro CA. Care of war veterans with mild traumatic brain injury--flawed perspectives. N Engl J Med. 2009 Apr 16;360(16):1588-91. doi: 10.1056/NEJMp0810606.
Hoge CW, McGurk D, Thomas JL, Cox AL, Engel CC, Castro CA. Mild traumatic brain injury in U.S. Soldiers returning from Iraq. N Engl J Med. 2008 Jan 31;358(5):453-63. doi: 10.1056/NEJMoa072972. Epub 2008 Jan 30.
Ingebrigtsen T, Waterloo K, Marup-Jensen S, Attner E, Romner B. Quantification of post-concussion symptoms 3 months after minor head injury in 100 consecutive patients. J Neurol. 1998 Sep;245(9):609-12.
International Committee of Medical Journal Editors. (2015, December). Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals. Retrieved February 24, 2016, from 2016 International Committee of Medical Journal editors: www.icmje.org
Janicak PG, O'Reardon JP, Sampson SM, Husain MM, Lisanby SH, Rado JT, Heart KL, Demitrack MA. Transcranial magnetic stimulation in the treatment of major depressive disorder: a comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment. J Clin Psychiatry. 2008 Feb;69(2):222-32.
King NS, Crawford S, Wenden FJ, Moss NE, Wade DT. The Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms commonly experienced after head injury and its reliability. J Neurol. 1995 Sep;242(9):587-92.
Ling G, Bandak F, Armonda R, Grant G, Ecklund J. Explosive blast neurotrauma. J Neurotrauma. 2009 Jun;26(6):815-25. doi: 10.1089/neu.2007.0484. Review.
Liu Y, Liang M, Zhou Y, He Y, Hao Y, Song M, Yu C, Liu H, Liu Z, Jiang T. Disrupted small-world networks in schizophrenia. Brain. 2008 Apr;131(Pt 4):945-61. doi: 10.1093/brain/awn018. Epub 2008 Feb 25.
Loo CK, McFarquhar TF, Mitchell PB. A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. Int J Neuropsychopharmacol. 2008 Feb;11(1):131-47. Epub 2007 Sep 20. Review.
Lopes da Silva, F. (2005(a)). EEG analysis: theory and practice. In E. Niedermeyer, & F. Lopes da Silva (Eds.), Electroencephalography; Basic Principles, Clinical Applications and Related Fields (pp. 1199-1231). Philadelphia, PA, USA: Lippincott, Williams and Wilkins.
Lopes da Silva, F. (2005(b)). Events-related potentials: methodology and quantification. In E. Niedermeyer, & F. Lopes da Silva, Electroencephalography: Basic Principles, Clinical Applications and Related Fields (pp. 991-1001). Philadelphia, Pennsylvania, US: Lippincott, Williams and Wilkins.
Luck, S. J. (2005). An Introduction to the Event-Related Potential Technique. Cambridge, MA, US: MIT Press.
Madulara, M. D., Francisco, P. A., Nawang, S., Arogancia, D. C., Cellucci, C. J., Rapp, P. E., & Albano, A. M. (2012). EEG transfer entropy tracks changes of information transfer on the onset of vision. International Journal of Modern Physics, 17, 9-18.
Mayer G, Aviram S, Walter G, Levkovitz Y, Bloch Y. Long-term follow-up of adolescents with resistant depression treated with repetitive transcranial magnetic stimulation. J ECT. 2012 Jun;28(2):84-6. doi: 10.1097/YCT.0b013e318238f01a.
Mayo Clinic Staff. (n.d.). Post-concussion syndrome. Retrieved September 15, 2015, from Mayo Clinic: http://www.mayoclinic.org/diseases-conditions/post-concussion-syndrome/basics/treatment/con-20032705
McCrea, M, ed; American Academy of Clinical Neuropsychology. (2008). Mild traumatic brain injury and postconcussion syndrome: the new evidence base for diagnosis and treatment. Oxford; New York: Oxford University Press.
Menon DK, Schwab K, Wright DW, Maas AI; Demographics and Clinical Assessment Working Group of the International and Interagency Initiative toward Common Data Elements for Research on Traumatic Brain Injury and Psychological Health. Position statement: definition of traumatic brain injury. Arch Phys Med Rehabil. 2010 Nov;91(11):1637-40. doi: 10.1016/j.apmr.2010.05.017. Review.
Mittenberg W, Strauman S. Diagnosis of mild head injury and the postconcussion syndrome. J Head Trauma Rehabil. 2000 Apr;15(2):783-91. Review.
Mittenberg W, Wittner MS, Miller LJ. Postconcussion syndrome occurs in children. Neuropsychology. 1997 Jul;11(3):447-52. Review.
Owen AM, McMillan KM, Laird AR, Bullmore E. N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Hum Brain Mapp. 2005 May;25(1):46-59.
Peskind ER, Petrie EC, Cross DJ, Pagulayan K, McCraw K, Hoff D, Hart K, Yu CE, Raskind MA, Cook DG, Minoshima S. Cerebrocerebellar hypometabolism associated with repetitive blast exposure mild traumatic brain injury in 12 Iraq war Veterans with persistent post-concussive symptoms. Neuroimage. 2011 Jan;54 Suppl 1:S76-82. doi: 10.1016/j.neuroimage.2010.04.008. Epub 2010 Apr 10.
Pinna GD, Maestri R, Torunski A, Danilowicz-Szymanowicz L, Szwoch M, La Rovere MT, Raczak G. Heart rate variability measures: a fresh look at reliability. Clin Sci (Lond). 2007 Aug;113(3):131-40.
Polich J, Criado JR. Neuropsychology and neuropharmacology of P3a and P3b. Int J Psychophysiol. 2006 May;60(2):172-85. Epub 2006 Feb 28. Review.
Porges SW. The polyvagal perspective. Biol Psychol. 2007 Feb;74(2):116-43. Epub 2006 Oct 16. Review.
Porta A, Bari V, Marchi A, De Maria B, Cysarz D, Van Leeuwen P, Takahashi AC, Catai AM, Gnecchi-Ruscone T. Complexity analyses show two distinct types of nonlinear dynamics in short heart period variability recordings. Front Physiol. 2015 Mar 10;6:71. doi: 10.3389/fphys.2015.00071. eCollection 2015.
Abdul Razak F, Jensen HJ. Quantifying 'causality' in complex systems: understanding transfer entropy. PLoS One. 2014 Jun 23;9(6):e99462. doi: 10.1371/journal.pone.0099462. eCollection 2014.
Richman JS, Moorman JR. Physiological time-series analysis using approximate entropy and sample entropy. Am J Physiol Heart Circ Physiol. 2000 Jun;278(6):H2039-49.
Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14. Review.
Runge J, Heitzig J, Marwan N, Kurths J. Quantifying causal coupling strength: a lag-specific measure for multivariate time series related to transfer entropy. Phys Rev E Stat Nonlin Soft Matter Phys. 2012 Dec;86(6 Pt 1):061121. Epub 2012 Dec 17.
Sakkas P, Mihalopoulou P, Mourtzouhou P, Psarros C, Masdrakis V, Politis A, Christodoulou GN. Induction of mania by rTMS: report of two cases. Eur Psychiatry. 2003 Jun;18(4):196-8.
Sigurdardottir S, Andelic N, Roe C, Jerstad T, Schanke AK. Post-concussion symptoms after traumatic brain injury at 3 and 12 months post-injury: a prospective study. Brain Inj. 2009 Jun;23(6):489-97. doi: 10.1080/02699050902926309.
Silver JM, McAllister TW. Forensic issues in the neuropsychiatric evaluation of the patient with mild traumatic brain injury. J Neuropsychiatry Clin Neurosci. 1997 Winter;9(1):102-13. Review.
Spencer, K. M. (2005). Averaging, detection and classification of single-trial ERPs. In T. M. Handy (Ed.), Event Related Potentials. A Methods Handbook (pp. 209-227). Cambridge, MA, US: MIT Press.
Stein MB, McAllister TW. Exploring the convergence of posttraumatic stress disorder and mild traumatic brain injury. Am J Psychiatry. 2009 Jul;166(7):768-76. doi: 10.1176/appi.ajp.2009.08101604. Epub 2009 May 15.
Taghva A, Oluigbo C, Corrigan J, Rezai AR. Posttraumatic stress disorder: neurocircuitry and implications for potential deep brain stimulation. Stereotact Funct Neurosurg. 2013;91(4):207-19. doi: 10.1159/000343148. Epub 2013 Mar 26. Review.
Taghva A, Silvetz R, Ring A, Kim KY, Murphy KT, Liu CY, Jin Y. Magnetic Resonance Therapy Improves Clinical Phenotype and EEG Alpha Power in Posttraumatic Stress Disorder. Trauma Mon. 2015 Nov;20(4):e27360. doi: 10.5812/traumamon.27360. Epub 2015 Nov 23.
Tanelian, T L; Jaycox, L, eds. (2008). Invisible wounds of war: psychological and cognitive injuries, their consequences, and services to assist recovery. RAND Center for Military Health Policy Research. Santa Monica, CA: RAND Corporation.
U.S. Department of Veterans Affairs. (2015, December 3). PTSD Checklist for DSM=5 (PCL-5). Retrieved from U.S. Department of Veterans Affairs PTSD: National Center for PTSD: http://www.ptsd.va.gov/professional/assessment/adult-sr/ptsd-checklist.asp
United States Army Medical Command. (2014, March 4). OSTG/MEDCOM Policy Memo 14-019. Inpatient and Emergency Department (ED) Aftercare; MEMORANDUM FOR COMMANDERS, MEDCOM REGIONAL MEDICAL COMMANDS. JBSA Fort Sam Houston, Texas, USA.
U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Biologics Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance. Health Qual Life Outcomes. 2006 Oct 11;4:79.
Management of Concussion/mTBI Working Group. VA/DoD Clinical Practice Guideline for Management of Concussion/Mild Traumatic Brain Injury. J Rehabil Res Dev. 2009;46(6):CP1-68.
Valenza G, Garcia RG, Citi L, Scilingo EP, Tomaz CA, Barbieri R. Nonlinear digital signal processing in mental health: characterization of major depression using instantaneous entropy measures of heartbeat dynamics. Front Physiol. 2015 Mar 13;6:74. doi: 10.3389/fphys.2015.00074. eCollection 2015.
Vinck M, Oostenveld R, van Wingerden M, Battaglia F, Pennartz CM. An improved index of phase-synchronization for electrophysiological data in the presence of volume-conduction, noise and sample-size bias. Neuroimage. 2011 Apr 15;55(4):1548-65. doi: 10.1016/j.neuroimage.2011.01.055. Epub 2011 Jan 27.
Wade DT, King NS, Wenden FJ, Crawford S, Caldwell FE. Routine follow up after head injury: a second randomised controlled trial. J Neurol Neurosurg Psychiatry. 1998 Aug;65(2):177-83.
Warden D. Military TBI during the Iraq and Afghanistan wars. J Head Trauma Rehabil. 2006 Sep-Oct;21(5):398-402.
Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroencephalogr Clin Neurophysiol. 1998 Jan;108(1):1-16.
Wippold FJ 2nd; Expert Panel on Neurologic Imaging. Focal neurologic deficit. AJNR Am J Neuroradiol. 2008 Nov;29(10):1998-2000.
World Health Organization, editors. (1993). The ICD-10 Classification of Mental and Behavioural Disorders Diagnostic Criteria for Research. Geneva: World Health Organization.