Clinical Trials Network
 Felipe Fregni, MD, PhD, Director of the Clinical Trials Network at the Center for Noninvasive Brain Stimulation A growing number of proof-of-principle and pilot studies reveal that repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) can modify (increase or decrease) cortical excitability focally, induce functionally relevant modulation of activity in distributed neural networks, and promote adaptive plastic changes that offer promise of therapeutic efficacy. In addition these two techniques are associated with mild adverse effects when applied following appropriate precautions and guidelines.
Indeed several studies from different centers have shown that noninvasive brain stimulation induces clinical benefits across different neuropsychiatric conditions – such as major depression, schizophrenia, chronic pain, stroke, epilepsy and Parkinson’s disease. Although the findings are encouraging, the evidence to date is still insufficient to endorse widespread clinical use of these techniques. Further phase-II and phase-III clinical trials are critical to increase the knowledge in this area and also to provide the necessary evidence to the clinical use of these techniques.
 We founded the Clinical Trials Network with the goal to promote multi-site, well-controlled clinical investigations on the use of noninvasive brain stimulation for the treatment of neuropsychiatric diseases. The goal of this initiative is to bring the presently existing research groups on noninvasive brain stimulation together in order launch collaborative clinical research programs and foster the development of noninvasive brain stimulation in the clinical practice.
Therefore the Clinical Trials Network is a network across different universities in different countries with the goal to exchange information on clinical trials using techniques of non-invasive brain stimulation and also conduct well-controlled, multi-site, collaborative studies. The Berenson-Allen Center for Noninvasive Brain Stimulation provides support with trial design, bioinformatics and biostatistical advice, as well as databasing and analysis infrastructure.
The following institutions and laboratories are joined in this collaborative effort to date. Other interested parties and institutions please contact Felipe Fregni, MD, PhD at ffregni@bidmc.harvard.edu.
Brazil
 Mackenzie University – Núcleo de Neurociências
Paulo Boggio, PhD
São Paulo, Brazil
http://www.mackenzie.br/
Email: psboggio@gmail.com
Centro de Dor e Neurocirurgia Funcional - Hospital 9 de Julho
Director: Claudio Fernandes Corrêa, MD
São Paulo, Brazil
http://www.h9j.com.br/
Email: cfcorrea@uol.com.br
Laboratório de Neurociências (Faculdade de Medicina) – Universidade de São Paulo
Angela Cristina Valle, PhD
São Paulo, Brazil
Email: acvalle@usp.br
Laboratório de Neurofisiologia Clínica – Universidade de São Paulo
Director: Kette Valente, MD, PhD
São Paulo, Brazil
Email: kettevalente@msn.com
Centro Brasileiro de Estimulação Magnética Transcraniana
Director: Roni Broder Cohen, MD
São Paulo, Brazil
http://www.transmagnet.med.br/
Email: tms@tmsbrasil.com.br
Germany
Laboratory of Clinical Neurophysiology – University of Gottingen
Michael Nitsche, MD
Gottingen, Germany
Email: mnitsch1@gwdg.de
Australia
 Centre for Neuromuscular and Neurological Disorders - University of Western Australia
Dylan Edwards, PhD
Perth, Australia
Email: dylane@cyllene.uwa.edu.au
Centre for the Mind - Australian National University
Director: Allan Snyder, PhD
Sydney, Australia
www.centreforthemind.com
Email: allan@centreforthemind.com
USA
Rehabilitation Medicine – University of Washington
Mark P. Jensen, PhD
Seattle, Washington
http://depts.washington.edu/rehab/contacts/jensen.html
mjensen@u.washington.edu
Harold Goodglass Boston University Aphasia Research Center - Boston University School of Medicine
Margaret Naeser, PhD
Boston, Massachusetts
Email: mnaeser@bu.edu
Summa Health System
Bradford Fenton, MD, PhD
Akron, Ohio
Email: fentonb@summa-health.org
Spain
Institut Guttmann, Hospital de Rehabilitació, Universitat Autonoma de Barcelona
Director of Research: Jose Maria Tormos, MD, PhD
Barcelona, Spain
http://www.guttmann.com/
Email: jmtormos@guttmann.com
Studies investigating the clinical effects of noninvasive brain stimulation
Studies investigating the clinical effects of noninvasive brain stimulation (please contact Felipe Fregni, MD, PhD at reprints@tmslab.org for reprints).
 Noninvasive brain stimulation in Parkinson’s disease
- Fregni F, Santos CM, Myczkowski ML, Rigolino R, Gallucci-Neto J, Barbosa ER, Valente KD, Pascual-Leone A, Marcolin MA. Repetitive transcranial magnetic stimulation is as effective as fluoxetine in the treatment of depression in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2004;75(8):1171-4.
- Fregni F, Simon DK, Wu A, Pascual-Leone A. Non-invasive brain stimulation for Parkinson’s disease: a systematic review and meta-analysis of the literature. J Neurol Neurosurg Psychiatry. 2005;76(12):1614-23.
- Dias AE, Barbosa ER, Coracini K, Maia F, Marcolin MA, Fregni F. Effects of repetitive transcranial magnetic stimulation on voice and speech in Parkinson’s disease. Acta Neurol Scand. 2006;113(2):92-9.
- Fregni F, Boggio PS, Santos MC, Lima M, Vieira AL, Rigonatti SP, Silva MT, Barbosa ER, Nitsche MA, Pascual-Leone A. Noninvasive cortical stimulation with transcranial direct current stimulation in Parkinson’s disease. Mov Disord. 2006;21(10):1693-702.
- Fregni F, Ono CR, Santos CM, Bermpohl F, Buchpiguel C, Barbosa ER, Marcolin MA, Pascual-Leone A, Valente KD. Effects of antidepressant treatment with rTMS and fluoxetine on brain perfusion in PD. Neurology. 2006;66(11):1629-37.
Noninvasive brain stimulation in stroke
- Naeser MA, Martin PI, Nicholas M, Baker EH, Seekins H, Kobayashi M, Theoret H, Fregni F, Maria-Tormos J, Kurland J, Doron KW, Pascual-Leone A. Improved picture naming in chronic aphasia after TMS to part of right Broca’s area: an open-protocol study. Brain Lang. 2005;93(1):95-105.
- Mansur CG, Fregni F, Boggio PS, Riberto M, Gallucci-Neto J, Santos CM, Wagner T, Rigonatti SP, Marcolin MA, Pascual-Leone A. A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients. Neurology. 2005;64(10):1802-4.
- Fregni F, Boggio PS, Valle AC, Rocha RR, Duarte J, Ferreira MJ, Wagner T, Fecteau S, Rigonatti SP, Riberto M, Freedman SD, Pascual-Leone A. A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients. Stroke. 2006;37(8):2115-22.
- Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJ, Lima MC, Rigonatti SP, Marcolin MA, Freedman SD, Nitsche MA, Pascual-Leone A. Transcranial direct current stimulation of the unaffected hemisphere in stroke patients. Neuroreport. 2005;16(14):1551-5.
- Fregni F, Pascual-Leone A. Hand motor recovery after stroke: tuning the orchestra to improve hand motor function. Cogn Behav Neurol. 2006;19(1):21-33.
Noninvasive brain stimulation in chronic pain
- Fregni F, DaSilva D, Potvin K, Ramos-Estebanez C, Cohen D, Pascual-Leone A, Freedman SD. Treatment of chronic visceral pain with brain stimulation. Ann Neurol. 2005;58(6):971-2.
- Fregni F, Boggio PS, Lima MC, Ferreira MJ, Wagner T, Rigonatti SP, Castro AW, Souza DR, Riberto M, Freedman SD, Nitsche MA, Pascual-Leone A. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain. 2006;122(1-2):197-209.
- Fregni F, Gimenes R, Valle AC, Ferreira MJ, Rocha RR, Natalle L, Bravo R, Rigonatti SP, Freedman SD, Nitsche MA, Pascual-Leone A, Boggio PS. A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Arthritis Rheum. 2006;54(12):3988-98.
- Fregni F, Freedman SD, Pascual-Leone A. Recent advances in the treatment of chronic pain with non-invasive brain stimulation techniques. Lancet Neurology. 2007 6(2):188-91..
Noninvasive brain stimulation in epilepsy
- 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;47(2):335-42.
- Fregni F, Otachi PT, Do Valle A, Boggio PS, Thut G, Rigonatti SP, Pascual-Leone A, Valente KD. A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy. Ann Neurol. 2006;60(4):447-55.
- Fregni F, Schachter SC, Pascual-Leone A. Transcranial magnetic stimulation treatment for epilepsy: can it also improve depression and vice versa? Epilepsy Behav. 2005;7(2):182-9.
Noninvasive brain stimulation in major depression
- Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7.
- Fregni F, Boggio PS, Nitsche MA, Marcolin MA, Rigonatti SP, Pascual-Leone A. Treatment of major depression with transcranial direct current stimulation. Bipolar Disord. 2006;8(2):203-4.
- Fregni F, Marcolin MA, Myczkowski ML, Amiaz R, Hasey G, Rumi D, Rosa M, Rigonatti SP, Camprodon J, Walpoth M, Heaslip J, Grunhaus L, Hausmann A, Pascual-Leone A. Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation. Int J Neuropsychopharmacol. 2006;9(6):641-54.
- Fregni F, Boggio PS, Nitsche MA, Rigonatti SP, Pascual-Leone A. Cognitive effects of repeated sessions of transcranial direct current stimulation in patients with depression. Depress Anxiety. 2006;23(8):482-4.
- Rosa MA, Gattaz WF, Pascual-Leone A, Fregni F, Rosa MO, Rumi DO, Myczkowski M, Silva MF, Mansur C, Rigonatti SP, Jacobsen Teixeira M, Marcolin MA. Comparison of repetitive transcranial magnetic stimulation and electroconvulsive therapy in unipolar non-psychotic refractory depression: a randomized, single-blind study. Int J Neuropsychopharmacol. 2006: pp. 1-10.
- Boggio PS, Rigonatti PS, Myczkowski ML, Nitsche MA, Pascual-Leone A, Fregni F. A randomized double-blind clinical trial on the efficacy of cortical DC stimulation in the treatment of major depression. International Journal of Neuropsychopharmacology, 2007 in press.
- Fregni F, Pascual-Leone A. Transcranial magnetic stimulation for the treatment of depression in neurologic disorders. Curr Psychiatry Rep. 2005;7(5):381-90.
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