Ignite Creation Date:
2024-05-06 @ 10:17 AM
Last Modification Date:
2024-10-26 @ 12:27 PM
Study NCT ID:
NCT03217123
Status:
COMPLETED
Last Update Posted:
2017-07-18
First Post:
2017-07-12
Brief Title:
Deep-brain Stimulation in Obsessive-compulsive Disorder Randomized Double-blinded Clinical Trial
Sponsor:
Hospital San Carlos Madrid
Organization:
Hospital San Carlos Madrid
Study Overview
Official Title:
Deep-brain Stimulation in Obsessive-compulsive Disorder
Status:
COMPLETED
Status Verified Date:
2017-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
10131
Brief Summary:
A prospective randomized double-blinded study was conducted in 7 OCD patients during which 4 electrode contacts along a striatal axis were stimulated bilaterally DBS electrode implantation followed a trajectory placing contact zero in nucleus accumbens a common target for OCD treatment with more proximal contacts placed in striatal segments defined using projections from prefrontal cortex subdivisions ventromedial orbitofrontal dorsolateral and anterior cingulate cortex
Detailed Description:
Patients Seven patients three men aged 21-50 years average std 3667 1464 and four women aged 28-46 years average 3525 814 suffering from treatment-refractory obsessive compulsive disorder participated in this study All patients scored 30 or higher in the Yale-Brown Obsessive-Compulsive Scale Y-BOCS They were considered as candidates to DBS for OCD by two independent psychiatrists An independent psychiatric surgery committee composed of one neurosurgeon one psychiatrist and one legal medicine expert agreed surgery indication was appropriate All patients provided written informed consent The study had approval from the Hospital Clínico San Carlos ethics committee
Pre-surgical Neuroimaging Before surgery all patients underwent 3T Siemens TRIO system Siemens Erlangen Germany MRI scanning Patients also performed an OCD symptom provocation task during fMRI scanning using modified version of the MOCSS Maudsley Obsessive-Compulsive Stimuli Set During scanning patients were presented with pictures of 4 classes of provocative stimuli 50 of each type 1 contaminationwashing 2 checking 3 hoarding 4 symmetryorder The study comprised 4 blocks pertaining to the 4 classes of provocative stimuli Each block consisted of ten 20-s alternating epochs in which subjects viewed either 10 provocative or 10 neutral pictures see Supplementary material for a full description Post-operative computed tomography CT scanning was used to determine correct electrode positioning
Neurosurgical procedure The target was selected for the distal electrode contact contact zero to be placed at the NAcc close to the bed nucleus of the stria terminalis 15 mm rostral to the anterior border of the anterior commissure 4 mm ventral to the AC-PC line and 7 mm lateral to the mid-sagittal plane Then the striatum was segmented using the deterministic DTI projections of the three subdivisions of the prefrontal cortex ventromedial vmPFC orbitofrontal OFC dorsolateral DLPFC plus the anterior cingulate cortex ACC A trajectory was planned for placing the rest of the contacts of a Medtronic Model 3391 stimulating macroelectrode at several points along the striatum avoiding the ventricles in such a way that each of the electrode contacts contacts 1 2 and 3 was closest to each segment of the striatum corresponding to OFC DLPFC and ACC
Deep-Brain Stimulation Protocol After surgery a random sequence of contact activations 0 Nacc12 and 3 including sham - was generated for each patient Each contact was activated using 130 Hz 60 ms and 45 V for three months the sham activation was 0 V following the patients individual sequence separated by one month of washout with the generator turned off
The study meets a double-blind longitudinal design Stimulation contact was set following a random series known only by the neurosurgeon with patient psychiatry and neuropsychology teams blind Psychiatric assessment was conducted each month and neuropsychological testing was performed after each activation and washout period
Symptom-provocation fMRI analysis Functional imaging data were analyzed using statistical parametric mapping SPM12 httpwwwfilionuclacukspm employing an epoch-related model The main symptoms for each patient was defined and used to construct a contrast of responses to provocation vs neutral pictures The ensuing contrasts were masked with an inclusive prefrontal mask and the statistical parametric map thresholded at P 0001 uncorrected Cluster extent was defined using AlphaSIM threshold P 005 Note that due to weak responses during symptom activation in patients 4 and 6 the SPMs for these patients were first thresholded at P 001 and 0005 uncorrected respectively After the clinical protocol had ended the projections to the cortical activated areas on the MOCSS for each patient in their main symptomatic dimension from the striatum were calculated using probabilistic tractography The connectivity between each of the contacts and the fMRI activations was calculated as the number of fibers of the projection of each contact sphere of diameter 4 mm around the contact to the cortical activated areas
Pre-surgical Neuroimaging Before surgery all patients underwent 3T Siemens TRIO system Siemens Erlangen Germany MRI scanning Patients also performed an OCD symptom provocation task during fMRI scanning using modified version of the MOCSS Maudsley Obsessive-Compulsive Stimuli Set During scanning patients were presented with pictures of 4 classes of provocative stimuli 50 of each type 1 contaminationwashing 2 checking 3 hoarding 4 symmetryorder The study comprised 4 blocks pertaining to the 4 classes of provocative stimuli Each block consisted of ten 20-s alternating epochs in which subjects viewed either 10 provocative or 10 neutral pictures see Supplementary material for a full description Post-operative computed tomography CT scanning was used to determine correct electrode positioning
Neurosurgical procedure The target was selected for the distal electrode contact contact zero to be placed at the NAcc close to the bed nucleus of the stria terminalis 15 mm rostral to the anterior border of the anterior commissure 4 mm ventral to the AC-PC line and 7 mm lateral to the mid-sagittal plane Then the striatum was segmented using the deterministic DTI projections of the three subdivisions of the prefrontal cortex ventromedial vmPFC orbitofrontal OFC dorsolateral DLPFC plus the anterior cingulate cortex ACC A trajectory was planned for placing the rest of the contacts of a Medtronic Model 3391 stimulating macroelectrode at several points along the striatum avoiding the ventricles in such a way that each of the electrode contacts contacts 1 2 and 3 was closest to each segment of the striatum corresponding to OFC DLPFC and ACC
Deep-Brain Stimulation Protocol After surgery a random sequence of contact activations 0 Nacc12 and 3 including sham - was generated for each patient Each contact was activated using 130 Hz 60 ms and 45 V for three months the sham activation was 0 V following the patients individual sequence separated by one month of washout with the generator turned off
The study meets a double-blind longitudinal design Stimulation contact was set following a random series known only by the neurosurgeon with patient psychiatry and neuropsychology teams blind Psychiatric assessment was conducted each month and neuropsychological testing was performed after each activation and washout period
Symptom-provocation fMRI analysis Functional imaging data were analyzed using statistical parametric mapping SPM12 httpwwwfilionuclacukspm employing an epoch-related model The main symptoms for each patient was defined and used to construct a contrast of responses to provocation vs neutral pictures The ensuing contrasts were masked with an inclusive prefrontal mask and the statistical parametric map thresholded at P 0001 uncorrected Cluster extent was defined using AlphaSIM threshold P 005 Note that due to weak responses during symptom activation in patients 4 and 6 the SPMs for these patients were first thresholded at P 001 and 0005 uncorrected respectively After the clinical protocol had ended the projections to the cortical activated areas on the MOCSS for each patient in their main symptomatic dimension from the striatum were calculated using probabilistic tractography The connectivity between each of the contacts and the fMRI activations was calculated as the number of fibers of the projection of each contact sphere of diameter 4 mm around the contact to the cortical activated areas
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None