Thalamic Stimulation of Patients in Vegetative or Minimally Conscious State

Minimally Conscious State Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01027572
• Other study ID #: RILM
• Status: Recruiting
• Phase: Phase 2
• First received: December 1, 2009
• Last updated: June 24, 2011
• Start date: July 2009
• Est. completion date: July 2012

Study information

• Verified date: June 2011
• Source: IRCCS Policlinico S. Matteo
• Contact: Roberto Imberti, MD
• Phone: +39-0382-502070
• Email: r.imberti[@]smatteo.pv.it
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5
• Est. completion date: July 2012
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Minimally Conscious State
• Persistent Vegetative State
• Vegetative State

Intervention

Device:
• Implantable neurostimulation system (Medtronic)
Thalamic stimulation will be performed using an implantable neurostimulation system

Locations

Country	Name	City	State
Italy	Istituto di Bioimmagini e Fisiologia Molecolare - CNR	Milano
Italy	Fondazione IRCCS "Casimiro Mondino"	Pavia
Italy	Fondazione IRCCS "Salvatore Maugeri"	Pavia

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Policlinico S. Matteo

Country where clinical trial is conducted

Italy, 

References & Publications (3)

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. — View 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. Erratum in: Nature. 2008 Mar 6;452(7183):120. Biondi, T [added]. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		1, 6, 12 months	No
Secondary	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.		1, 6, 12 months	No