Clinical trial NCT02950506: Transcranial Direct Current Stimulation and Cognitive Remediation Therapy for Interictal Dysfunction in Epilepsy
Official title: Transcranial Direct Current Stimulation and Cognitive Remediation Therapy for Interictal Dysfunction in Epilepsy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Epilepsy
Keywords: Interictal
Cognitive
Dysfunction
tDCS
transcranial direct current stimulation
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2016-11-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to investigate whether tDCS enhances the effect of cognitive remediation therapy on cognition and functional outcome in patients with epilepsy. There has been evidence that working memory performance is enhanced in healthy subjects. Acute tDCS studies have found improvements in working memory performance in subjects with other neurological diseases. To date, there have been no published studies examining whether can enhance learning during multi-session cognitive remediation over 2 weeks in subjects with epilepsy. This study could have potential application as a non-invasive clinical intervention for interictal dysfunction in epilepsy.

Detailed description: Epilepsy is a chronic neurological disorder affecting 50 million people worldwide. Patients suffer not only from recurring seizures, but also from cognitive deficits despite adequate treatment control. Cognitive remediation therapy (CRT) is a therapeutic intervention that has recently shown promise in improving cognitive impairment in many neuropsychological disorders. Transcranial direct current stimulation (tDCS) is a non-invasive method that modulates cortical excitability. It works by applying weak electrical currents to the scalp that induce acute modifications of neuronal membrane potentials, producing long-lasting changes in the bioelectric activity of underlying brain tissue. It is postulated that tDCS enhances benefit gained through cognitive remediation therapy. These interventions have yet to be combined with each other for the treatment of interictal dysfunction in patients with epilepsy. The goal of the study is to investigate whether the introduction of tDCS in addition to CRT is effective in the treatment of cognitive impairment in patients suffering from epilepsy.

Eligibility criteria: Inclusion Criteria:

* Age 18-64
* Epilepsy diagnosis confirmed by the UMN Comprehensive Epilepsy Center
* Complete seizure logs of the type in standard clinic use at the UMN Comprehensive Epilepsy Center for at least 12 weeks prior to study entry
* Stable CNS medications for the 2 weeks prior to the initiation visit and expected to continue with current medication doses for the two weeks of the intervention
* No diagnosis of mental retardation (IQ not less than 70) or pervasive developmental disorder
* At least one subtest of learning and memory less than --1.5 SD
* Sufficient spoken English so as to be able to comprehend testing procedures
* Competent and willing to provide consent

Exclusion Criteria:

* Occurrence of generalized convulsive status epilepticus or of complex partial status epilepticus within 1 year prior to study entry
* Occurrence of more than 1 generalized tonic-clonic (GTC) seizure per month, or more than 4 complex partial (CP) seizures per week, as reported in the subject's seizure logs for 12 weeks prior to study entry
* Occurrence of GTC seizure within 48 hours before testing
* Any anti-epileptic medication changes or hospitalizations in the previous 4 weeks
* Additional neurologic disorder other epilepsy and cognitive dysfunctions
* History of metallic cranial plates, screws, or implanted devices
* History of craniotomy

Primary outcomes:
measure: Cogstate Brief Battery
timeFrame: Change from baseline to 5 days, 1 month, and 3 months after last intervention visit.
measure: Rey Auditory Verbal Learning Test (AVLT)
timeFrame: Change from baseline to 5 days, 1 month, and 3 months after last intervention visit.
measure: Picture Sequence Memory Test
timeFrame: Change from baseline to 5 days, 1 month, and 3 months after last intervention visit.
measure: Flanker Inhibitory Control and Attention Task
timeFrame: Change from baseline to 5 days, 1 month, and 3 months after last intervention visit.
measure: Dimensional Change Card Sort Test
timeFrame: Change from baseline to 5 days, 1 month, and 3 months after last intervention visit.
Secondary outcomes:
measure: Oral Symbol Digit Test
timeFrame: Change from baseline to 5 days, 1 month, and 3 months after last intervention visit.
measure: Cogstate Brief Battery
timeFrame: Change from baseline to 5 days, 1 month, and 3 months after last intervention visit.
measure: Quality of Life
timeFrame: Change from baseline to 5 days, 1 month, and 3 months after last intervention visit.
Other outcomes:
Locations:
city: Saint Louis Park
country: United States
facility: University of Minnesota Comprehensive Epilepsy Center(MINCEP)
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Thomas Henry, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Andrews SC, Hoy KE, Enticott PG, Daskalakis ZJ, Fitzgerald PB. Improving working memory: the effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex. Brain Stimul. 2011 Apr;4(2):84-9. doi: 10.1016/j.brs.2010.06.004. Epub 2010 Jul 11.
citation: Benedict, Ralph H B, David Schretlen, Lowell Groninger, and Jason Brandt. 1998. "Hopkins Verbal Learning Test - Revised: Normative Data and Analysis of Inter-Form and Test-Retest Reliability." The Clinical Neuropsychologist 12 (1): 43-55.
citation: Benson N, Hulac DM, Kranzler JH. Independent examination of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV): what does the WAIS-IV measure? Psychol Assess. 2010 Mar;22(1):121-30. doi: 10.1037/a0017767.
citation: Boggio PS, Ferrucci R, Rigonatti SP, Covre P, Nitsche M, Pascual-Leone A, Fregni F. Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease. J Neurol Sci. 2006 Nov 1;249(1):31-8. doi: 10.1016/j.jns.2006.05.062. Epub 2006 Jul 14.
citation: Brandt, J. & Benedict, R. (2001). Hopkins Verbal Learning Test-Revised: Professional Manual. PAR: Florida
citation: Brunelin J, Mondino M, Haesebaert F, Saoud M, Suaud-Chagny MF, Poulet E. Efficacy and safety of bifocal tDCS as an interventional treatment for refractory schizophrenia. Brain Stimul. 2012 Jul;5(3):431-432. doi: 10.1016/j.brs.2011.03.010. Epub 2011 Apr 24. No abstract available.
citation: Brunoni AR, Amadera J, Berbel B, Volz MS, Rizzerio BG, Fregni F. A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Int J Neuropsychopharmacol. 2011 Sep;14(8):1133-45. doi: 10.1017/S1461145710001690. Epub 2011 Feb 15.
citation: Cramer JA, Perrine K, Devinsky O, Bryant-Comstock L, Meador K, Hermann B. Development and cross-cultural translations of a 31-item quality of life in epilepsy inventory. Epilepsia. 1998 Jan;39(1):81-8. doi: 10.1111/j.1528-1157.1998.tb01278.x.
citation: Del Felice A, Magalini A, Masiero S. Slow-oscillatory Transcranial Direct Current Stimulation Modulates Memory in Temporal Lobe Epilepsy by Altering Sleep Spindle Generators: A Possible Rehabilitation Tool. Brain Stimul. 2015 May-Jun;8(3):567-73. doi: 10.1016/j.brs.2015.01.410. Epub 2015 Jan 30.
citation: Denboer, John W, Christopher Nicholls, Corrine Corte, and Kali Chestnut. 2014. "National Institutes of Health Toolbox Cognition Battery." Archives of Clinical Neuropsychology: The Official Journal of the National Academy of Neuropsychologists, August. doi:10.1093/arclin/acu033.
citation: Dikmen SS, Bauer PJ, Weintraub S, Mungas D, Slotkin J, Beaumont JL, Gershon R, Temkin NR, Heaton RK. Measuring episodic memory across the lifespan: NIH Toolbox Picture Sequence Memory Test. J Int Neuropsychol Soc. 2014 Jul;20(6):611-9. doi: 10.1017/S1355617714000460. Epub 2014 Jun 24.
citation: Engelberts NH, Klein M, Ader HJ, Heimans JJ, Trenite DG, van der Ploeg HM. The effectiveness of cognitive rehabilitation for attention deficits in focal seizures: a randomized controlled study. Epilepsia. 2002 Jun;43(6):587-95. doi: 10.1046/j.1528-1157.2002.29401.x.
citation: Falleti MG, Maruff P, Collie A, Darby DG. Practice effects associated with the repeated assessment of cognitive function using the CogState battery at 10-minute, one week and one month test-retest intervals. J Clin Exp Neuropsychol. 2006 Oct;28(7):1095-112. doi: 10.1080/13803390500205718.
citation: Fregni F, Thome-Souza S, Nitsche MA, Freedman SD, Valente KD, Pascual-Leone A. A controlled clinical trial of cathodal DC polarization in patients with refractory epilepsy. Epilepsia. 2006 Feb;47(2):335-42. doi: 10.1111/j.1528-1167.2006.00426.x.
citation: Fregni F, Boggio PS, Nitsche M, Bermpohl F, Antal A, Feredoes E, Marcolin MA, Rigonatti SP, Silva MT, Paulus W, Pascual-Leone A. Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Exp Brain Res. 2005 Sep;166(1):23-30. doi: 10.1007/s00221-005-2334-6. Epub 2005 Jul 6.
citation: Gazzaley A. Influence of early attentional modulation on working memory. Neuropsychologia. 2011 May;49(6):1410-24. doi: 10.1016/j.neuropsychologia.2010.12.022. Epub 2010 Dec 22.
citation: Haut KM, Lim KO, MacDonald A 3rd. Prefrontal cortical changes following cognitive training in patients with chronic schizophrenia: effects of practice, generalization, and specificity. Neuropsychopharmacology. 2010 Aug;35(9):1850-9. doi: 10.1038/npp.2010.52. Epub 2010 Apr 28.
citation: Heaton RK, Akshoomoff N, Tulsky D, Mungas D, Weintraub S, Dikmen S, Beaumont J, Casaletto KB, Conway K, Slotkin J, Gershon R. Reliability and validity of composite scores from the NIH Toolbox Cognition Battery in adults. J Int Neuropsychol Soc. 2014 Jul;20(6):588-98. doi: 10.1017/S1355617714000241. Epub 2014 Jun 24.
citation: Henry TR, Roman DD. Presurgical epilepsy localization with interictal cerebral dysfunction. Epilepsy Behav. 2011 Feb;20(2):194-208. doi: 10.1016/j.yebeh.2010.12.008. Epub 2011 Jan 22.
citation: Johnson MD, Lim HH, Netoff TI, Connolly AT, Johnson N, Roy A, Holt A, Lim KO, Carey JR, Vitek JL, He B. Neuromodulation for brain disorders: challenges and opportunities. IEEE Trans Biomed Eng. 2013 Mar;60(3):610-24. doi: 10.1109/TBME.2013.2244890. Epub 2013 Feb 1.
citation: Jo JM, Kim YH, Ko MH, Ohn SH, Joen B, Lee KH. Enhancing the working memory of stroke patients using tDCS. Am J Phys Med Rehabil. 2009 May;88(5):404-9. doi: 10.1097/PHM.0b013e3181a0e4cb.
citation: Lin JJ, Mula M, Hermann BP. Uncovering the neurobehavioural comorbidities of epilepsy over the lifespan. Lancet. 2012 Sep 29;380(9848):1180-92. doi: 10.1016/S0140-6736(12)61455-X.
citation: Loring DW, Strauss E, Hermann BP, Barr WB, Perrine K, Trenerry MR, Chelune G, Westerveld M, Lee GP, Meador KJ, Bowden SC. Differential neuropsychological test sensitivity to left temporal lobe epilepsy. J Int Neuropsychol Soc. 2008 May;14(3):394-400. doi: 10.1017/S1355617708080582.
citation: Mattioli F, Bellomi F, Stampatori C, Capra R, Miniussi C. Neuroenhancement through cognitive training and anodal tDCS in multiple sclerosis. Mult Scler. 2016 Feb;22(2):222-30. doi: 10.1177/1352458515587597. Epub 2015 May 26.
citation: Medalia A, Revheim N, & Herlands T. Cognitive remediation for psychological disorders: therapist guide. Treatments that work. Oxford ; New York: Oxford University Press, 2009.
citation: Golden, Charles J. 2002. "Stroop Color and Word Test : A Manual for Clinical and Experimental Uses". Wood Dale, IL.
citation: Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Paulus W, Hummel F, Boggio PS, Fregni F, Pascual-Leone A. Transcranial direct current stimulation: State of the art 2008. Brain Stimul. 2008 Jul;1(3):206-23. doi: 10.1016/j.brs.2008.06.004. Epub 2008 Jul 1.
citation: Nowinski CJ, Victorson D, Cavazos JE, Gershon R, Cella D. Neuro-QOL and the NIH Toolbox: implications for epilepsy. Therapy. 2010 Sep 1;7(5):533-540. doi: 10.2217/thy.10.55.
citation: Oliveira JF, Zanao TA, Valiengo L, Lotufo PA, Bensenor IM, Fregni F, Brunoni AR. Acute working memory improvement after tDCS in antidepressant-free patients with major depressive disorder. Neurosci Lett. 2013 Mar 14;537:60-4. doi: 10.1016/j.neulet.2013.01.023. Epub 2013 Jan 28.
citation: Oyegbile TO, Dow C, Jones J, Bell B, Rutecki P, Sheth R, Seidenberg M, Hermann BP. The nature and course of neuropsychological morbidity in chronic temporal lobe epilepsy. Neurology. 2004 May 25;62(10):1736-42. doi: 10.1212/01.wnl.0000125186.04867.34.
citation: Ponds RW, Hendriks M. Cognitive rehabilitation of memory problems in patients with epilepsy. Seizure. 2006 Jun;15(4):267-73. doi: 10.1016/j.seizure.2006.02.011. Epub 2006 Mar 23.
citation: Poreisz C, Boros K, Antal A, Paulus W. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull. 2007 May 30;72(4-6):208-14. doi: 10.1016/j.brainresbull.2007.01.004. Epub 2007 Jan 24.
citation: Rzezak P, Moschetta SP, Lima E, Castro CX, Vincentiis S, Coan AC, Guerreiro C, Filho GB, Valente KD. Distinct domains of impulsivity are impaired in juvenile myoclonic epilepsy but not in temporal lobe epilepsy. Epilepsy Behav. 2015 Apr;45:44-8. doi: 10.1016/j.yebeh.2015.02.028. Epub 2015 Mar 25.
citation: Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.
citation: Spencer-Smith M, Klingberg T. Benefits of a working memory training program for inattention in daily life: a systematic review and meta-analysis. PLoS One. 2015 Mar 20;10(3):e0119522. doi: 10.1371/journal.pone.0119522. eCollection 2015.
citation: Strauss E, Sherman E, Spreen O (2006). Rey Auditory Verbal Learning Test. In Compendium of Neuropsychological Tests (3rd Edition) Oxford University Press.776- 807
citation: Tam JW, Schmitter-Edgecombe M. The role of processing speed in the Brief Visuospatial Memory Test - revised. Clin Neuropsychol. 2013;27(6):962-72. doi: 10.1080/13854046.2013.797500. Epub 2013 May 20.
citation: Weintraub S, Dikmen SS, Heaton RK, Tulsky DS, Zelazo PD, Slotkin J, Carlozzi NE, Bauer PJ, Wallner-Allen K, Fox N, Havlik R, Beaumont JL, Mungas D, Manly JJ, Moy C, Conway K, Edwards E, Nowinski CJ, Gershon R. The cognition battery of the NIH toolbox for assessment of neurological and behavioral function: validation in an adult sample. J Int Neuropsychol Soc. 2014 Jul;20(6):567-78. doi: 10.1017/S1355617714000320. Epub 2014 Jun 24.