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出境医 / 临床实验 / Brain Tissue Imprint (BTI)

Brain Tissue Imprint (BTI)

Study Description
Brief Summary:

This exploratory study aims to validate the collection and analysis of brain tissue imprints during the DBS by using a CE marked Medical Device in patients presenting one of the following five disorders: Parkinson's disease (PD), essential tremor (ET), dystonia (DYS), Obsessive compulsive disorder (OCD) and Tourette Syndrome (TS).

The Brain Tissue Imprint project is focused on the DBS surgical procedure, which constitutes an appropriate method to collect brain tissue imprints by taking advantage of the direct and transitory contact at the extremity of the dilator with adjacent brain tissue. Indeed, during this step, micro-fragments of brain material spontaneously adhere to the dilator tip. It is this imprinting process that allows to collect what is defined as "brain tissue imprints. This approach is part of the standard surgical procedure of the SCP without major change or complications.


Condition or disease Intervention/treatment Phase
Parkinson Disease Neurologic Disorder Device: Brain Tissue Imprint Not Applicable

Detailed Description:

Deep brain stimulation (DBS) has become the standard functional neurosurgery treatment for drug resistant Parkinson's disease (PD) patients. It has also demonstrated its efficacy to treat various movement disorders as well as neurological and psychiatric disorders. The subthalamic nucleus (STN), the globus pallidus internal (GPi) or the ventral intermediate nucleus of the thalamus (VIM) are the major targets of DBS.

Access to pathological brain tissue in living PD patients or other neurological diseases is a key issue for the discovery of new therapeutic targets and the development of potential curative therapies. In this context, DBS offers a unique access to the pathological brain. In the standard surgical procedure, to prepare the way for the final electrode, the surgeon uses a dilator that is lowered gently through the cerebral parenchyma up to the target. It has been shown that during this step, brain tissue fragments adhere to the extremity of the dilator. However, the major drawback of the standard dilator lies in the fact that its end is in contact with several brain regions before reaching the targeted nucleus. Therefore, it is difficult to guarantee the origin of the collected tissue micro-fragments. In order to optimize the specificity of the harvested imprints, the investgator will use a dedicated CE marked medical device that consists of a guide tube and a stylet instead of the dilator used in DBS surgical procedure. The objective of this study is to validate brain tissue imprints collection in PD, ET, DYS, OCD and TS.

The BTI will be specifically collected from the targeted implantation site corresponding to the STN, the GPi and the VIM. Moreover, the tip of the electrode (and therefore the BTI) often reaches the substantia negra pars compacta (SNpc) because of its proximity with the STN. The ability to perform BTI in the SNpc is of highly interest since it is the structure containing the neurons that degenerate gradually and massively throughout the pathological process of Parkinson's disease.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Stimulation cérébrale Profonde et Empreinte Tissulaire : Une Nouvelle stratégie Pour la Recherche Biologique in Vivo Dans la Maladie de Parkinson, Les TOC, la Dystonie, le Tremblement Essentiel et le Syndrome Gilles de la Tourette.
Estimated Study Start Date : May 2019
Estimated Primary Completion Date : April 30, 2021
Estimated Study Completion Date : April 30, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: Brain Tissue Imprint
Evaluation and validation of the samples collected during the brain tissue imprint procedure using a CE marked Medical Device in patients presenting one of the following five disorders: Parkinson's disease (PD), essential tremor (ET), dystonia (DYS), Obsessive compulsive disorder (OCD) and Tourette Syndrome (TS).
 Device: Brain Tissue Imprint

Brain Tissue Imprint procedure (BTI) is performed during DBS surgery. Before the implantation of the electrode, the surgeon uses a dilator. It is a rigid stylet with a blunt end, intended to prepare the way for the final electrode. This dilator is lowered gently through the cerebral parenchyma up to the target then removed to be replaced by the electrode.

In our BTI study, the standard dilator used in DBS surgery will be replaced by a CE marked Medical Device. This brain imprint kit will be used for each hemisphere. The procedure is the following:

  • The guide tube with the first stylet is set up to the target
  • Withdrawal of the first stylet and insertion of the second stylet for one minute to have a spontaneous and adequate tissue adhesion
  • Withdrawal of the guide tube containing the stylet. This last step will prevent contamination of the harvested material on the stylet during the removal.
Outcome Measures
Primary Outcome Measures :
  1. Validation of the collection of brain tissue fragments on the BTI device during the DBS surgical procedure [ Time Frame: The evaluation of the collection of brain tissue fragments will be performed in the surgery room when the BTI device is removed from the patient and inserted in the collection tube ]
    Visual assessment of the presence or the absence of a tissue micro-fragment. The presence or absence of blood contamination will also be notified


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eligible patients for deep brain stimulation surgery
  • Patients affiliated to social security or benefiting of a similar insurance scheme
  • Patients having signed a consent to participate to the study

Exclusion Criteria:

  • Patient not eligible for deep brain stimulation surgery
  • Pregnant women or nursing mothers
  • Persons deprived of liberty by judicial or administrative decision
  • Persons unable to express their consent or legally protected
  • Persons in period of disqualification for another interventional research
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Stéphan Chabardès, Pr +33 4 76 76 75 59 SChabardes@chu-grenoble.fr
Contact: Claire Bollart +33 4 76 76 56 09 CBollart@chu-grenoble.fr

Locations
Layout table for location information
France
Grenoble Hospital - CHUGA
Grenoble, Isere, France, 38043
Contact: Stéphan Chabardès, Pr    +33 4 76 76 75 59    SChabardes@chu-grenoble.fr   
Contact: Dodji D'Almeida    +33 4 56 52 03 89    DDalmeida@chu-grenoble.fr   
Sponsors and Collaborators
University Hospital, Grenoble
Investigators
Layout table for investigator information
Principal Investigator: Stéphan Chabardès, Pr Grenoble Hospital - Service de Neurochirurgie, CHUGA
Tracking Information
First Submitted Date  ICMJE April 9, 2019
First Posted Date  ICMJE April 26, 2019
Last Update Posted Date April 26, 2019
Estimated Study Start Date  ICMJE May 2019
Estimated Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 25, 2019) 		Validation of the collection of brain tissue fragments on the BTI device during the DBS surgical procedure [ Time Frame: The evaluation of the collection of brain tissue fragments will be performed in the surgery room when the BTI device is removed from the patient and inserted in the collection tube ]
Visual assessment of the presence or the absence of a tissue micro-fragment. The presence or absence of blood contamination will also be notified
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Brain Tissue Imprint
Official Title  ICMJE Stimulation cérébrale Profonde et Empreinte Tissulaire : Une Nouvelle stratégie Pour la Recherche Biologique in Vivo Dans la Maladie de Parkinson, Les TOC, la Dystonie, le Tremblement Essentiel et le Syndrome Gilles de la Tourette.
Brief Summary

This exploratory study aims to validate the collection and analysis of brain tissue imprints during the DBS by using a CE marked Medical Device in patients presenting one of the following five disorders: Parkinson's disease (PD), essential tremor (ET), dystonia (DYS), Obsessive compulsive disorder (OCD) and Tourette Syndrome (TS).

The Brain Tissue Imprint project is focused on the DBS surgical procedure, which constitutes an appropriate method to collect brain tissue imprints by taking advantage of the direct and transitory contact at the extremity of the dilator with adjacent brain tissue. Indeed, during this step, micro-fragments of brain material spontaneously adhere to the dilator tip. It is this imprinting process that allows to collect what is defined as "brain tissue imprints. This approach is part of the standard surgical procedure of the SCP without major change or complications.
Detailed Description

Deep brain stimulation (DBS) has become the standard functional neurosurgery treatment for drug resistant Parkinson's disease (PD) patients. It has also demonstrated its efficacy to treat various movement disorders as well as neurological and psychiatric disorders. The subthalamic nucleus (STN), the globus pallidus internal (GPi) or the ventral intermediate nucleus of the thalamus (VIM) are the major targets of DBS.

Access to pathological brain tissue in living PD patients or other neurological diseases is a key issue for the discovery of new therapeutic targets and the development of potential curative therapies. In this context, DBS offers a unique access to the pathological brain. In the standard surgical procedure, to prepare the way for the final electrode, the surgeon uses a dilator that is lowered gently through the cerebral parenchyma up to the target. It has been shown that during this step, brain tissue fragments adhere to the extremity of the dilator. However, the major drawback of the standard dilator lies in the fact that its end is in contact with several brain regions before reaching the targeted nucleus. Therefore, it is difficult to guarantee the origin of the collected tissue micro-fragments. In order to optimize the specificity of the harvested imprints, the investgator will use a dedicated CE marked medical device that consists of a guide tube and a stylet instead of the dilator used in DBS surgical procedure. The objective of this study is to validate brain tissue imprints collection in PD, ET, DYS, OCD and TS.

The BTI will be specifically collected from the targeted implantation site corresponding to the STN, the GPi and the VIM. Moreover, the tip of the electrode (and therefore the BTI) often reaches the substantia negra pars compacta (SNpc) because of its proximity with the STN. The ability to perform BTI in the SNpc is of highly interest since it is the structure containing the neurons that degenerate gradually and massively throughout the pathological process of Parkinson's disease.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE
  • Parkinson Disease
  • Neurologic Disorder
Intervention  ICMJE Device: Brain Tissue Imprint

Brain Tissue Imprint procedure (BTI) is performed during DBS surgery. Before the implantation of the electrode, the surgeon uses a dilator. It is a rigid stylet with a blunt end, intended to prepare the way for the final electrode. This dilator is lowered gently through the cerebral parenchyma up to the target then removed to be replaced by the electrode.

In our BTI study, the standard dilator used in DBS surgery will be replaced by a CE marked Medical Device. This brain imprint kit will be used for each hemisphere. The procedure is the following:

  • The guide tube with the first stylet is set up to the target
  • Withdrawal of the first stylet and insertion of the second stylet for one minute to have a spontaneous and adequate tissue adhesion
  • Withdrawal of the guide tube containing the stylet. This last step will prevent contamination of the harvested material on the stylet during the removal.
Study Arms  ICMJE Experimental: Brain Tissue Imprint
Evaluation and validation of the samples collected during the brain tissue imprint procedure using a CE marked Medical Device in patients presenting one of the following five disorders: Parkinson's disease (PD), essential tremor (ET), dystonia (DYS), Obsessive compulsive disorder (OCD) and Tourette Syndrome (TS).
Intervention: Device: Brain Tissue Imprint
Publications *
  • Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J. Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol. 1987;50(1-6):344-6.
  • Perlmutter JS, Mink JW. Deep brain stimulation. Annu Rev Neurosci. 2006;29:229-57. Review.
  • Holtzheimer PE, Mayberg HS. Deep brain stimulation for psychiatric disorders. Annu Rev Neurosci. 2011;34:289-307. doi: 10.1146/annurev-neuro-061010-113638. Review.
  • Hariz M, Blomstedt P, Zrinzo L. Future of brain stimulation: new targets, new indications, new technology. Mov Disord. 2013 Nov;28(13):1784-92. doi: 10.1002/mds.25665. Epub 2013 Oct 7. Review.
  • Fontaine D, Lanteri-Minet M, Ouchchane L, Lazorthes Y, Mertens P, Blond S, Geraud G, Fabre N, Navez M, Lucas C, Dubois F, Sol JC, Paquis P, Lemaire JJ. Anatomical location of effective deep brain stimulation electrodes in chronic cluster headache. Brain. 2010 Apr;133(Pt 4):1214-23. doi: 10.1093/brain/awq041. Epub 2010 Mar 17.
  • Laxton AW, Tang-Wai DF, McAndrews MP, Zumsteg D, Wennberg R, Keren R, Wherrett J, Naglie G, Hamani C, Smith GS, Lozano AM. A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease. Ann Neurol. 2010 Oct;68(4):521-34. doi: 10.1002/ana.22089.
  • Boëx C, Seeck M, Vulliémoz S, Rossetti AO, Staedler C, Spinelli L, Pegna AJ, Pralong E, Villemure JG, Foletti G, Pollo C. Chronic deep brain stimulation in mesial temporal lobe epilepsy. Seizure. 2011 Jul;20(6):485-90. doi: 10.1016/j.seizure.2011.03.001. Epub 2011 Apr 12.
  • Lozano AM, Giacobbe P, Hamani C, Rizvi SJ, Kennedy SH, Kolivakis TT, Debonnel G, Sadikot AF, Lam RW, Howard AK, Ilcewicz-Klimek M, Honey CR, Mayberg HS. A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression. J Neurosurg. 2012 Feb;116(2):315-22. doi: 10.3171/2011.10.JNS102122. Epub 2011 Nov 18.
  • Torres N, Chabardes S, Piallat B, Devergnas A, Benabid AL. Body fat and body weight reduction following hypothalamic deep brain stimulation in monkeys: an intraventricular approach. Int J Obes (Lond). 2012 Dec;36(12):1537-44. doi: 10.1038/ijo.2011.271. Epub 2012 Feb 21.
  • Luigjes J, van den Brink W, Feenstra M, van den Munckhof P, Schuurman PR, Schippers R, Mazaheri A, De Vries TJ, Denys D. Deep brain stimulation in addiction: a review of potential brain targets. Mol Psychiatry. 2012 Jun;17(6):572-83. doi: 10.1038/mp.2011.114. Epub 2011 Sep 20. Review.
  • Benabid AL, Chabardes S, Mitrofanis J, Pollak P. Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease. Lancet Neurol. 2009 Jan;8(1):67-81. doi: 10.1016/S1474-4422(08)70291-6. Review.
  • Zaccaria A, Bouamrani A, Chabardès S, El Atifi M, Seigneuret E, Lobrinus JA, Dubois-Dauphin M, Berger F, Burkhard PR. Deep brain stimulation-associated brain tissue imprints: a new in vivo approach to biological research in human Parkinson's disease. Mol Neurodegener. 2016 Jan 28;11:12. doi: 10.1186/s13024-016-0077-4.
  • Crecelius A, Götz A, Arzberger T, Fröhlich T, Arnold GJ, Ferrer I, Kretzschmar HA. Assessing quantitative post-mortem changes in the gray matter of the human frontal cortex proteome by 2-D DIGE. Proteomics. 2008 Mar;8(6):1276-91. doi: 10.1002/pmic.200700728.
  • Mexal S, Berger R, Adams CE, Ross RG, Freedman R, Leonard S. Brain pH has a significant impact on human postmortem hippocampal gene expression profiles. Brain Res. 2006 Aug 23;1106(1):1-11. doi: 10.1016/j.brainres.2006.05.043. Epub 2006 Jul 14.
  • Chariot P, Witt K, Pautot V, Porcher R, Thomas G, Zafrani ES, Lemaire F. Declining autopsy rate in a French hospital: physician's attitudes to the autopsy and use of autopsy material in research publications. Arch Pathol Lab Med. 2000 May;124(5):739-45.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: April 25, 2019) 		40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2021
Estimated Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Eligible patients for deep brain stimulation surgery
  • Patients affiliated to social security or benefiting of a similar insurance scheme
  • Patients having signed a consent to participate to the study

Exclusion Criteria:

  • Patient not eligible for deep brain stimulation surgery
  • Pregnant women or nursing mothers
  • Persons deprived of liberty by judicial or administrative decision
  • Persons unable to express their consent or legally protected
  • Persons in period of disqualification for another interventional research
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03929406
Other Study ID Numbers  ICMJE 2018-A03001-54
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Grenoble
Study Sponsor  ICMJE University Hospital, Grenoble
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Stéphan Chabardès, Pr Grenoble Hospital - Service de Neurochirurgie, CHUGA
PRS Account University Hospital, Grenoble
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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