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Thalamic Stimulation of Patients in Vegetative or Minimally Conscious State (CATS\)

Primary Purpose

Vegetative State, Minimally Conscious State

Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Implantable neurostimulation system (Medtronic)
Sponsored by
IRCCS Policlinico S. Matteo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Vegetative State focused on measuring Vegetative state, Minimally conscious state, Thalamic stimulation

Eligibility Criteria

10 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male and female patients stably in VS or MCS from at least 6 months, 10 to 65 years old.
  • Patients must fulfil the neuroimaging criteria described later
  • Patients must fulfil neurophysiologic criteria as described later

Exclusion Criteria:

  • Inability to provide the informed consent by the legal representative
  • Age < 10 years and > 65 years
  • Pregnancy
  • Expected life span < 1 year
  • Presence of infectious disease not treatable
  • Brain pathology not correlated with VS or MCS

Inclusion criteria based on MRI imaging of the brain. The following criteria specify the location and extent of damage to the brain which determine the inclusion or exclusion from the study.

Before inclusion into the study all patients will be submitted to a complete MRI of the brain comprehensive of T1 and T2 weighted and flair sequences. Patients with a history of traumatic injury that were not submitted to cervical MRI at the time or after the initial injury will be submitted to a cervical MRI before admission to the study. A MRI scanner with field strength of at least 1.5 tesla will be used for imaging the brain and the cervical spinal cord. The volumetric extent of the damage will be estimated by using an image analysis program (e.g. IMAGE, NIH) after the neuroradiologist has traced the contour of the injured structures in all MRI images of the brain.

Thalamus: bilateral absence of damage of the centromedian/parafascicularis complex and of the entire area of the intralaminar nuclei. The remaining structures of the thalami should not be damaged for an extent greater than 40% of the total volume of the two thalami.

Frontal lobes: at least one lobe should not be damaged to an extent superior to 20% of the volume. Absence of lesion of the Broca's area in the left (or dominant) hemisphere.

Temporal lobes: absence of damage to the posterior two third of the left or dominant temporal lobe. The extent of the lesions in the remaining structures of the temporal lobes should be less than 70% of the total volume of the lobes.

Parietal lobes: lesion volume in at least one parietal lobe should be less than 30%.

Occipital lobes: lesion volume in at least one occipital lobe should be less than 30%. The visual cortex should be spared in at least one lobe.

Hypothalamus: absence of lesions. Mesencephalon: absence of lesions in the region located between the substantia nigra and the bases of the colliculi. Unilateral lesions ventral to the substantia nigra are permitted.

Pons: absence of lesions unless unilateral and limited to the ventral third of the pons.

Cerebellum: Absence of lesions larger than 80% of the total volume; the deep nuclei of at least one side of the cerebellum should be intact.

Medulla: absence of lesions unless limited to one pyramid. Cervical spinal cord: absence of lesions All patients should be free from hydrocephalus or the hydrocephalus should be treated with a shunt prior to thalamic implant.

Exclusion criteria based on MRI imaging of the brain. All patients who do not fulfill the criteria for inclusion based on MRI imaging of the brain will be excluded.

Inclusion Criteria based on neurophysiologic parameters

  • Patients will be studied by continuous electroencephalography. Patients showing EEG desynchronization for at least 5% of the period studied will be included.
  • Acoustic evoked potentials must be present at least at one side. V wave prolongation will be accepted.
  • Somato-sensory evoked potentials must be present at least at one side. Increased latency of N20 will be accepted.

Exclusion Criteria based on neurophysiologic criteria All patients who do not fulfill the criteria for inclusion based on neurophysiologic parameters will be excluded.

Sites / Locations

  • Istituto di Bioimmagini e Fisiologia Molecolare - CNRRecruiting
  • Fondazione IRCCS "Casimiro Mondino"Recruiting
  • Fondazione IRCCS "Salvatore Maugeri"Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Thalamic stimulation

Arm Description

Patients in Vegetative or Minimally Conscious State

Outcomes

Primary Outcome Measures

Efficacy of thalamic stimulation evaluated by the administration of the CRS-R and Coma/Near Coma scales and comparing the results obtained with those of the pre-implant evaluation.

Secondary Outcome Measures

Changes in the length of desynchronization performed by continuous EEG recording and spectral analysis. Evaluate which patients in Vegetative State and Minimally Conscious State can benefit from central thalamic stimulation.

Full Information

First Posted
December 1, 2009
Last Updated
June 24, 2011
Sponsor
IRCCS Policlinico S. Matteo
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1. Study Identification

Unique Protocol Identification Number
NCT01027572
Brief Title
Thalamic Stimulation of Patients in Vegetative or Minimally Conscious State
Acronym
CATS\
Official Title
Efficacy of Thalamic Stimulation in the Treatment of Patients in Vegetative State and Minimally Conscious State From at Least Six Months. A Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2011
Overall Recruitment Status
Unknown status
Study Start Date
July 2009 (undefined)
Primary Completion Date
July 2011 (Anticipated)
Study Completion Date
July 2012 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
IRCCS Policlinico S. Matteo

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Rationale. The investigators hypothesize that bilateral electrical central thalamic stimulation of patients in Vegetative State and Minimally Conscious State from at least 6 months could improve the level of responsiveness. Aims. Evaluate the efficacy of bilateral electrical central thalamic stimulation in patients in Vegetative State and Minimally Conscious State. Study Design. Patients in Vegetative State and Minimally Conscious State from at least 6 months because of traumatic brain injury, hypoxic or ischemic brain injury will be evaluated to confirm the diagnosis according to the recent literature criteria. Then patients will be investigated by magnetic resonance (MRI), EEG and evoked potentials to evaluate eligibility. Patients included into the study will be implanted with electrodes, targeting the centromedian/parafascicularis nucleus complex of the thalamus bilaterally. In the following months patients will be repeatedly evaluated using the CRS-R and Coma/Near Coma scales and the neurophysiologic parameters (EEG, evoked potentials) to assess the effects of thalamic stimulation. fMRI,DTI and MRS will be performed prior and after thalamic stimulation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vegetative State, Minimally Conscious State
Keywords
Vegetative state, Minimally conscious state, Thalamic stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
5 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Thalamic stimulation
Arm Type
Experimental
Arm Description
Patients in Vegetative or Minimally Conscious State
Intervention Type
Device
Intervention Name(s)
Implantable neurostimulation system (Medtronic)
Intervention Description
Thalamic stimulation will be performed using an implantable neurostimulation system
Primary Outcome Measure Information:
Title
Efficacy of thalamic stimulation evaluated by the administration of the CRS-R and Coma/Near Coma scales and comparing the results obtained with those of the pre-implant evaluation.
Time Frame
1, 6, 12 months
Secondary Outcome Measure Information:
Title
Changes in the length of desynchronization performed by continuous EEG recording and spectral analysis. Evaluate which patients in Vegetative State and Minimally Conscious State can benefit from central thalamic stimulation.
Time Frame
1, 6, 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female patients stably in VS or MCS from at least 6 months, 10 to 65 years old. Patients must fulfil the neuroimaging criteria described later Patients must fulfil neurophysiologic criteria as described later Exclusion Criteria: Inability to provide the informed consent by the legal representative Age < 10 years and > 65 years Pregnancy Expected life span < 1 year Presence of infectious disease not treatable Brain pathology not correlated with VS or MCS Inclusion criteria based on MRI imaging of the brain. The following criteria specify the location and extent of damage to the brain which determine the inclusion or exclusion from the study. Before inclusion into the study all patients will be submitted to a complete MRI of the brain comprehensive of T1 and T2 weighted and flair sequences. Patients with a history of traumatic injury that were not submitted to cervical MRI at the time or after the initial injury will be submitted to a cervical MRI before admission to the study. A MRI scanner with field strength of at least 1.5 tesla will be used for imaging the brain and the cervical spinal cord. The volumetric extent of the damage will be estimated by using an image analysis program (e.g. IMAGE, NIH) after the neuroradiologist has traced the contour of the injured structures in all MRI images of the brain. Thalamus: bilateral absence of damage of the centromedian/parafascicularis complex and of the entire area of the intralaminar nuclei. The remaining structures of the thalami should not be damaged for an extent greater than 40% of the total volume of the two thalami. Frontal lobes: at least one lobe should not be damaged to an extent superior to 20% of the volume. Absence of lesion of the Broca's area in the left (or dominant) hemisphere. Temporal lobes: absence of damage to the posterior two third of the left or dominant temporal lobe. The extent of the lesions in the remaining structures of the temporal lobes should be less than 70% of the total volume of the lobes. Parietal lobes: lesion volume in at least one parietal lobe should be less than 30%. Occipital lobes: lesion volume in at least one occipital lobe should be less than 30%. The visual cortex should be spared in at least one lobe. Hypothalamus: absence of lesions. Mesencephalon: absence of lesions in the region located between the substantia nigra and the bases of the colliculi. Unilateral lesions ventral to the substantia nigra are permitted. Pons: absence of lesions unless unilateral and limited to the ventral third of the pons. Cerebellum: Absence of lesions larger than 80% of the total volume; the deep nuclei of at least one side of the cerebellum should be intact. Medulla: absence of lesions unless limited to one pyramid. Cervical spinal cord: absence of lesions All patients should be free from hydrocephalus or the hydrocephalus should be treated with a shunt prior to thalamic implant. Exclusion criteria based on MRI imaging of the brain. All patients who do not fulfill the criteria for inclusion based on MRI imaging of the brain will be excluded. Inclusion Criteria based on neurophysiologic parameters Patients will be studied by continuous electroencephalography. Patients showing EEG desynchronization for at least 5% of the period studied will be included. Acoustic evoked potentials must be present at least at one side. V wave prolongation will be accepted. Somato-sensory evoked potentials must be present at least at one side. Increased latency of N20 will be accepted. Exclusion Criteria based on neurophysiologic criteria All patients who do not fulfill the criteria for inclusion based on neurophysiologic parameters will be excluded.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Roberto Imberti, MD
Phone
+39-0382-502070
Email
r.imberti@smatteo.pv.it
First Name & Middle Initial & Last Name or Official Title & Degree
Lorenzo Magrassi, MD
Email
l.magrassi@smatteo.pv.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roberto Imberti, MD
Organizational Affiliation
Fondazione IRCCS Policlinico S. Matteo - Pavia - Italy
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Lorenzo Magrassi, MD
Organizational Affiliation
Fondazione IRCCS Policlinico S. Matteo, Pavia and University of Pavia - Italy
Official's Role
Study Chair
Facility Information:
Facility Name
Istituto di Bioimmagini e Fisiologia Molecolare - CNR
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabriele EM Biella, MD, PhD
Email
gabriele.biella@ibfm.cnr.it
First Name & Middle Initial & Last Name & Degree
Gabriele EM Biella, MD, PhD
Facility Name
Fondazione IRCCS "Casimiro Mondino"
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefano Bastianello, MD
Email
stefano.bastianello@mondino.it
First Name & Middle Initial & Last Name & Degree
Stefano Bastianello, MD
Facility Name
Fondazione IRCCS "Salvatore Maugeri"
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caterina Pistarini, MD
Email
caterina.pistarini@fsm.it
First Name & Middle Initial & Last Name & Degree
Caterina Pistarini, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
17671503
Citation
Schiff ND, Giacino JT, Kalmar K, Victor JD, Baker K, Gerber M, Fritz B, Eisenberg B, Biondi T, O'Connor J, Kobylarz EJ, Farris S, Machado A, McCagg C, Plum F, Fins JJ, Rezai AR. Behavioural improvements with thalamic stimulation after severe traumatic brain injury. Nature. 2007 Aug 2;448(7153):600-3. doi: 10.1038/nature06041. Erratum In: Nature. 2008 Mar 6;452(7183):120. Biondi, T [added].
Results Reference
background
PubMed Identifier
17509244
Citation
Lombardi F, Gatta G, Sacco S, Muratori A, Carolei A. The Italian version of the Coma Recovery Scale-Revised (CRS-R). Funct Neurol. 2007 Jan-Apr;22(1):47-61.
Results Reference
background
PubMed Identifier
15986737
Citation
Yamamoto T, Kobayashi K, Kasai M, Oshima H, Fukaya C, Katayama Y. DBS therapy for the vegetative state and minimally conscious state. Acta Neurochir Suppl. 2005;93:101-4. doi: 10.1007/3-211-27577-0_17.
Results Reference
background
PubMed Identifier
26745476
Citation
Magrassi L, Maggioni G, Pistarini C, Di Perri C, Bastianello S, Zippo AG, Iotti GA, Biella GE, Imberti R. Results of a prospective study (CATS) on the effects of thalamic stimulation in minimally conscious and vegetative state patients. J Neurosurg. 2016 Oct;125(4):972-981. doi: 10.3171/2015.7.JNS15700. Epub 2016 Jan 8.
Results Reference
derived

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Thalamic Stimulation of Patients in Vegetative or Minimally Conscious State

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