Stimulation magnétique transcrânienne répétitive Dans le Traitement Des Troubles Obsessionnels Compulsifs
Repetitive Transcranial Magnetic Stimulation in Obsessive Compulsive Disorder
Sponsors
Source
University Hospital, Grenoble
Oversight Info
Has Dmc
Yes
Brief Summary
Evaluate the therapeutic effect of a functional Magnetic Resonance Imaging (fMRI)-guided and
robotized neuronavigated theta burst Transcranial Magnetic Stimulation (TMS) targeting right
inferior frontal region in resistant obsessive compulsive disorder (OCD) in a double-blind,
randomized, placebo-controlled, monocentric study.
Detailed Description
This study evaluates the therapeutic effect of a fMRI-guided and robotized neuronavigated
theta burst Transcranial Magnetic Stimulation (TMS) targeting right inferior frontal region
in resistant obsessive compulsive disorder (OCD) in a double-blind, randomized,
placebo-controlled, monocentric study. The study will also assess the interest of some
clinical, neuropsychological, neuroimaging, electrophysiological variables in response
prediction, besides physiopathological information.
There is an increasing interest in developping treatments for resistant OCD, which are not
responding to the conventional treatment, represented by pharmacotherapy associated to
cognitive behavioral therapy. Repetitive TMS represents a promising non invasive brain
stimulation approach, but efficacy, best available brain target, optimal responder profile
and stimulation parameters need to be further documented.
In this study, the included patients will be randomly assigned to an active (theta burst TMS)
or sham-placebo treatment group. TMS will be added to their stable pharmacotherapy. The brain
target, the right inferior frontal region, involved in the inhibition control brain network,
will be defined in a personalized manner via a fMRI paradigm for each patient. TMS will be
delivered daily for 2 successive weeks. Measures of different clinical, neuropsychological ,
electrophysiological (cortical excitability) variables will be performed at baseline, as well
as at the end of the TMS course, and 1 week after. Other assessments are planned at 3 and 6
months, in order to highlight the evolution of the potential benefit.
Overall Status
Recruiting
Start Date
2015-05-01
Completion Date
2020-05-01
Primary Completion Date
2017-11-01
Phase
N/A
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Change from baseline of the score at the Yale - Brown Obsessive and Compulsive Scale |
at baseline and at day 21 |
Secondary Outcome
Measure |
Time Frame |
|
Score of Montgomery and Asberg Depression Rating Scale, as a Measure of effects on Mood (depression) |
At baseline, at day 21, day 90, day 180 |
|
Score of Young Mania Rating Scale, as a Measure of effects on Mood (hyperthymia) |
At baseline, at day 21, day 90, day 180 |
|
Score of Multidimensional Assessment of Thymic States Scale as a Measure of effects on Emotional Reactivity |
At baseline, at day 21, day 90, day 180 |
|
Number of patients with Side effects as a measure of Safety and Tolerability |
for each session of Transcranial Magnetic Stimulation, at day 15, day 21, day 90, day 180 |
|
Inferior Frontal Region Activity (percentage of the BOLD signal change (parameter estimates beta) |
at baseline (day 0) |
|
Fractional Anisotropy (FA), mean and radial diffusivity (MD, RD), tracti integrity of the inhibition network, |
at day 0 (baseline) |
|
Yale - Brown Obsessive and Compulsion Scale score after the TMS treatment as an evaluation of the persistence of the clinical benefit |
day 15, day 90 and day 180 after the inclusion. |
|
Cortical Excitability |
baseline - day 15 - day 21 - day 90 - day 180 |
|
Evaluation of Impulsivity using specific scales |
At baseline, at day 21, day 90, day 180 |
|
Evaluation of the Clinical global State |
at baseline, day 15, day 21, day 90, day 180 |
|
type of side effects (pain, paresthesia, other) as a measure of Safety and Tolerability |
for each session of Transcranial Magnetic Stimulation, at day 15, day 21, day 90, day 180 |
Enrollment
56
Condition
Intervention
Intervention Type
Device
Intervention Name
Description
modulation of the electrical activity of the right inferior frontal gyrus cortex in order to reduce Obsessive Compulsive Disorders symptoms by Active Transcranial Magnetic Stimulation (TMS) targeting the right frontal inferior gyrus, 2 sessions per day, each session 5min30 day, during 10 consecutive days, using theta burst stimulation and using a TMS neuronavigated robot
Arm Group Label
active Transcranial Magnetic Stimulation
Intervention Type
Device
Intervention Name
Description
Sham rTMS will be delivered using non active magnetic coil, targeting the right frontal inferior gyrus, 2 sessions per day, each session 5min30 day, during 10 consecutive days, using TMS neuronavigated robot. A subjective sensation will be obtained via frontal dermic electrical stimulation.
Arm Group Label
Placebo
Eligibility
Criteria
Inclusion Criteria:
- Volunteer subjects with Obsessive Compulsive Disorders (OCD) according to the
Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR) criteria and
validated by an experimented clinician following instruments like SCID (Structured
Clinical Interview for DSM IV) or MINI (Mini-International Neuropsychiatric Interview)
- with or without associated tics ("Gilles de la Tourette" Syndrome)
- Age > 18 years old
- Y-BOCS score > 20 and CGI (Clinical Global Impression Scale) score ≥ 4
- Resistant patients to standard treatments - where treatment resistance is defined by
partial but insufficient response (Global Assessment of Functioning score GAF score <
60 and/or reduction of Yale Brown Obsessions and Compulsion Scale score < 35%) or lack
of response to previous well conducted treatment including:
- pharmacotherapy : optimal tolerated dose and adequate duration (> 12 weeks) of at
least 2 Serotonin Reuptake Inhibitors (selective serotonin reuptake inhibitors,
clomipramine), and one augmentation strategy (adjunction of an antipsychotic -
such as risperidone or olanzapine or aripiprazole - or lithium or buspirone) ;
- psychotherapy (at least 6 months of cognitive and behavioral therapy)
Exclusion Criteria:
- other primary diagnosis than OCD (comorbid tics and depression are tolerated)
- comorbid diagnosis of schizophrenia/ psychotic disorder, bipolar disorder, substance
abuse or dependance
- medical condition involving cognitive decline and affecting brain structures such as
Parkinson disease, dementia, multiple sclerosis, HIV (human immunodeficiency virus)
infection, lupus etc.
- Magnetic Resonance Imaging exclusion criteria (ferromagnetic implants etc)
- common TMS exclusion criteria (neurological condition with an increased risk of
seizure, cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute,
unstable cardiac disease, intracranial implants (e.g. cochlear implants, electrodes,
aneurysm clips, stimulators... ) or any other metal object within or near the head,
excluding the mouth, that cannot be safely removed will be excluded
- Current use of any investigational drug
- pregnancy / breast feeding patients
- visual or auditive important deficit
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Mircea POLOSAN, Professor |
Principal Investigator |
Institut National de la Santé Et de la Recherche Médicale, France |
Overall Contact
Location
Facility |
Status |
Contact |
|
CHU de Grenoble - Pavillon Dominique Villars Grenoble Rhone Alpes 38000 France |
Recruiting |
Location Countries
Country
France
Verification Date
2018-05-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
2014-A00668-39
Number Of Arms
2
Arm Group
Arm Group Label
active Transcranial Magnetic Stimulation
Arm Group Type
Active Comparator
Description
Active Transcranial Magnetic Stimulation (TMS) targeting the right frontal inferior gyrus, 2 sessions per day, each session 5min30 day, during 10 consecutive days, Using theta burst stimulation and using Transcranial Magnetic Stimulation navigator and robot
Arm Group Label
Placebo
Arm Group Type
Placebo Comparator
Description
Placebo comparator, using non active magnetic coil, targeting the right frontal inferior gyrus, 2 sessions per day, each session 5min30 day, during 10 consecutive days, using theta burst stimulation and using Transcranial Magnetic Stimulation navigator and robot
Firstreceived Results Date
N/A
Reference
Citation
Heyman I, Mataix-Cols D, Fineberg NA. Obsessive-compulsive disorder. BMJ. 2006 Aug 26;333(7565):424-9. Review.
PMID
16931840
Citation
Denys D. Pharmacotherapy of obsessive-compulsive disorder and obsessive-compulsive spectrum disorders. Psychiatr Clin North Am. 2006 Jun;29(2):553-84, xi. Review.
PMID
16650723
Citation
Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex. Lancet. 1985 May 11;1(8437):1106-7.
PMID
2860322
Citation
Baxter LR Jr, Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE. Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls. Arch Gen Psychiatry. 1987 Mar;44(3):211-8. Erratum in: Arch Gen Psychiatry 1987 Sep;44(9):800.
PMID
3493749
Citation
Li CT, Chen MH, Juan CH, Huang HH, Chen LF, Hsieh JC, Tu PC, Bai YM, Tsai SJ, Lee YC, Su TP. Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study. Brain. 2014 Jul;137(Pt 7):2088-98. doi: 10.1093/brain/awu109. Epub 2014 May 10.
PMID
24817188
Citation
Plewnia C, Pasqualetti P, Große S, Schlipf S, Wasserka B, Zwissler B, Fallgatter A. Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. J Affect Disord. 2014 Mar;156:219-23. doi: 10.1016/j.jad.2013.12.025. Epub 2013 Dec 28.
PMID
24411682
Citation
Di Lazzaro V, Pilato F, Dileone M, Profice P, Oliviero A, Mazzone P, Insola A, Ranieri F, Meglio M, Tonali PA, Rothwell JC. The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex. J Physiol. 2008 Aug 15;586(16):3871-9. doi: 10.1113/jphysiol.2008.152736. Epub 2008 Jun 19.
PMID
18566003
Citation
Prasko J, Pasková B, Záleský R, Novák T, Kopecek M, Bares M, Horácek J. The effect of repetitive transcranial magnetic stimulation (rTMS) on symptoms in obsessive compulsive disorder. A randomized, double blind, sham controlled study. Neuro Endocrinol Lett. 2006 Jun;27(3):327-32.
PMID
16816829
Citation
Sarkhel S, Sinha VK, Praharaj SK. Adjunctive high-frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) was not effective in obsessive-compulsive disorder but improved secondary depression. J Anxiety Disord. 2010 Jun;24(5):535-9. doi: 10.1016/j.janxdis.2010.03.011. Epub 2010 Mar 29.
PMID
20392594
Citation
Sack AT, Cohen Kadosh R, Schuhmann T, Moerel M, Walsh V, Goebel R. Optimizing functional accuracy of TMS in cognitive studies: a comparison of methods. J Cogn Neurosci. 2009 Feb;21(2):207-21. doi: 10.1162/jocn.2009.21126.
PMID
18823235
Citation
Sachdev PS, McBride R, Loo CK, Mitchell PB, Malhi GS, Croker VM. Right versus left prefrontal transcranial magnetic stimulation for obsessive-compulsive disorder: a preliminary investigation. J Clin Psychiatry. 2001 Dec;62(12):981-4.
PMID
11780880
Citation
Wu CC, Tsai CH, Lu MK, Chen CM, Shen WC, Su KP. Theta-burst repetitive transcranial magnetic stimulation for treatment-resistant obsessive-compulsive disorder with concomitant depression. J Clin Psychiatry. 2010 Apr;71(4):504-6. doi: 10.4088/JCP.09l05426blu.
PMID
20409448
Citation
Aron AR, Fletcher PC, Bullmore ET, Sahakian BJ, Robbins TW. Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans. Nat Neurosci. 2003 Feb;6(2):115-6. Erratum in: Nat Neurosci. 2003 Dec;6(12):1329.
PMID
12536210
Citation
Chambers CD, Bellgrove MA, Stokes MG, Henderson TR, Garavan H, Robertson IH, Morris AP, Mattingley JB. Executive "brake failure" following deactivation of human frontal lobe. J Cogn Neurosci. 2006 Mar;18(3):444-55.
PMID
16513008
Citation
Verbruggen F, Aron AR, Stevens MA, Chambers CD. Theta burst stimulation dissociates attention and action updating in human inferior frontal cortex. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13966-71. doi: 10.1073/pnas.1001957107. Epub 2010 Jul 14.
PMID
20631303
Citation
Duncan J, Owen AM. Common regions of the human frontal lobe recruited by diverse cognitive demands. Trends Neurosci. 2000 Oct;23(10):475-83. Review.
PMID
11006464
Citation
Verbruggen F, Schneider DW, Logan GD. How to stop and change a response: the role of goal activation in multitasking. J Exp Psychol Hum Percept Perform. 2008 Oct;34(5):1212-28. doi: 10.1037/0096-1523.34.5.1212.
PMID
18823206
Citation
Boucher L, Palmeri TJ, Logan GD, Schall JD. Inhibitory control in mind and brain: an interactive race model of countermanding saccades. Psychol Rev. 2007 Apr;114(2):376-97. Review.
PMID
17500631
Citation
Chambers CD, Bellgrove MA, Gould IC, English T, Garavan H, McNaught E, Kamke M, Mattingley JB. Dissociable mechanisms of cognitive control in prefrontal and premotor cortex. J Neurophysiol. 2007 Dec;98(6):3638-47. Epub 2007 Oct 17.
PMID
17942624
Citation
Aron AR, Behrens TE, Smith S, Frank MJ, Poldrack RA. Triangulating a cognitive control network using diffusion-weighted magnetic resonance imaging (MRI) and functional MRI. J Neurosci. 2007 Apr 4;27(14):3743-52.
PMID
17409238
Citation
Swann N, Tandon N, Canolty R, Ellmore TM, McEvoy LK, Dreyer S, DiSano M, Aron AR. Intracranial EEG reveals a time- and frequency-specific role for the right inferior frontal gyrus and primary motor cortex in stopping initiated responses. J Neurosci. 2009 Oct 7;29(40):12675-85. doi: 10.1523/JNEUROSCI.3359-09.2009.
PMID
19812342
Citation
Hampshire A, Chamberlain SR, Monti MM, Duncan J, Owen AM. The role of the right inferior frontal gyrus: inhibition and attentional control. Neuroimage. 2010 Apr 15;50(3):1313-9. doi: 10.1016/j.neuroimage.2009.12.109. Epub 2010 Jan 4.
PMID
20056157
Citation
Chikazoe J, Jimura K, Asari T, Yamashita K, Morimoto H, Hirose S, Miyashita Y, Konishi S. Functional dissociation in right inferior frontal cortex during performance of go/no-go task. Cereb Cortex. 2009 Jan;19(1):146-52. doi: 10.1093/cercor/bhn065. Epub 2008 Apr 28.
PMID
18445602
Citation
Lüders H, Lesser RP, Dinner DS, Morris HH, Wyllie E, Godoy J. Localization of cortical function: new information from extraoperative monitoring of patients with epilepsy. Epilepsia. 1988;29 Suppl 2:S56-65. Erratum in: Epilepsia 1988 Nov-Dec;29(6):828.
PMID
3168959
Citation
Johansen-Berg H, Behrens TE, Robson MD, Drobnjak I, Rushworth MF, Brady JM, Smith SM, Higham DJ, Matthews PM. Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13335-40. Epub 2004 Aug 30.
PMID
15340158
Citation
Marsh R, Horga G, Parashar N, Wang Z, Peterson BS, Simpson HB. Altered activation in fronto-striatal circuits during sequential processing of conflict in unmedicated adults with obsessive-compulsive disorder. Biol Psychiatry. 2014 Apr 15;75(8):615-22. doi: 10.1016/j.biopsych.2013.02.004. Epub 2013 Mar 13.
PMID
23489416
Citation
de Wit SJ, de Vries FE, van der Werf YD, Cath DC, Heslenfeld DJ, Veltman EM, van Balkom AJ, Veltman DJ, van den Heuvel OA. Presupplementary motor area hyperactivity during response inhibition: a candidate endophenotype of obsessive-compulsive disorder. Am J Psychiatry. 2012 Oct;169(10):1100-8. doi: 10.1176/appi.ajp.2012.12010073. Erratum in: Am J Psychiatry. 2012 Nov 1;169(11):1218.
PMID
23032388
Citation
Stein DJ, Goodman WK, Rauch SL. The cognitive-affective neuroscience of obsessive-compulsive disorder. Curr Psychiatry Rep. 2000 Aug;2(4):341-6. Review.
PMID
11122979
Citation
Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6.
PMID
15664172
Citation
Stokes MG, Chambers CD, Gould IC, Henderson TR, Janko NE, Allen NB, Mattingley JB. Simple metric for scaling motor threshold based on scalp-cortex distance: application to studies using transcranial magnetic stimulation. J Neurophysiol. 2005 Dec;94(6):4520-7. Epub 2005 Aug 31.
PMID
16135552
Citation
Stokes MG, Chambers CD, Gould IC, English T, McNaught E, McDonald O, Mattingley JB. Distance-adjusted motor threshold for transcranial magnetic stimulation. Clin Neurophysiol. 2007 Jul;118(7):1617-25. Epub 2007 May 23.
PMID
17524764
Citation
Buch ER, Mars RB, Boorman ED, Rushworth MF. A network centered on ventral premotor cortex exerts both facilitatory and inhibitory control over primary motor cortex during action reprogramming. J Neurosci. 2010 Jan 27;30(4):1395-401. doi: 10.1523/JNEUROSCI.4882-09.2010.
PMID
20107065
Citation
Neubert FX, Mars RB, Buch ER, Olivier E, Rushworth MF. Cortical and subcortical interactions during action reprogramming and their related white matter pathways. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13240-5. doi: 10.1073/pnas.1000674107. Epub 2010 Jul 9.
PMID
20622155
Citation
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.
PMID
19833552
Acronym
MAGTOC
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Study First Submitted
January 8, 2015
Study First Submitted Qc
August 30, 2016
Study First Posted
August 31, 2016
Last Update Submitted
May 9, 2018
Last Update Submitted Qc
May 9, 2018
Last Update Posted
May 15, 2018
ClinicalTrials.gov processed this data on January 17, 2020
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.