Effects of Deep Brain Stimulation of the Dentate Nucleus on Cerebellar Ataxia

Recruiting

Phase N/A Results N/A

Trial Description

Cerebellar ataxias are a group of disorders caused by cerebellar affections, for which currently no specific treatment is available. Some limited studies verified the effects of cerebellar transcranial magnetic stimulation (TMS) on ataxic symptoms, with good results. The hypothesis is that cerebellar TMS could improve ataxic symptoms in some patients and in these patients, chronic cerebellar stimulation through deep brain stimulation could be a therapeutic option. The rationale is to stimulate the dentate nucleus of the cerebellum in order to balance the functional asymmetry observed between both motor cortices after chronic cerebellar lesions.

Detailed Description

Ten patients with cerebellar ataxia will be included in our protocol. Ataxia might be due to several aetiologies, from degenerative to genetic and vascular diseases. The initial focus is vascular and spinal cerebellar ataxias. The participants will be submitted to a neuronavigation protocol for the precise location of the dentate nucleus contralateral to the most symptomatic side. After that, the participants will be randomly assigned to 5 active or 5 placebo sessions of 1Hz TMS over the located area. After the first 5 sessions and a period of at least 4 weeks washout, the participants will cross over and receive other 5 sessions, active or sham. Clinical and video evaluations will be conducted before and after active and sham cluster of sessions. The good responders, i.e., with over than 30% of improvement after the active section will be eligible to bilateral dentate nucleus DBS. After that, again, a cross-over double blind on-off stimulation will be performed. Each period (on or 0ff-stimulation) will last 4 weeks.

Conditions

Interventions

  • Deep brain stimulation on stimulation - active Device
    Intervention Desc: bilateral deep brain stimulation reaching the dentate nucleus turned ON - phase active
    ARM 1: Kind: Experimental
    Label: Deep brain stimulation
    Description: Intervention type: device (deep brain stimulation of the dentate nucleus in cerebellum) will remained turned ON during 3 months
    ARM 2: Kind: Experimental
    Label: Device - deep brain stimulation ON
    Description: Intervention type: device (deep brain stimulation of the dentate nucleus in cerebellum). The intervention is a device called deep brain stimulation bilaterally placed in the sub thalamic nucleus. The stimulation will remained turned ON during 3 months - phase 1 - blinded and continuous during the open-label phase
  • Deep brain stimulation off stimulation - sham Device
    Intervention Desc: bilateral deep brain stimulation reaching the dentate nucleus turned OFF - phase sham
    ARM 1: Kind: Experimental
    Label: Sham stimulation
    Description: Sham stimulation: device (deep brain stimulation of the dentate nucleus in cerebellum) will remained turned OFF during 3 months
    ARM 2: Kind: Experimental
    Label: Device - deep brain stimulation Sham
    Description: Sham stimulation: device (deep brain stimulation of the dentate nucleus in cerebellum). Intervention type: device (deep brain stimulation of the dentate nucleus in cerebellum). The intervention is a device called deep brain stimulation bilaterally placed in the sub thalamic nucleus. During the sham stimulation the intervention will remained turned OFF during 3 months

Outcomes

Type Measure Time Frame Safety Issue
Primary Primary outcome - change in Scale for the assessment and rating of ataxia - SARA change in the SARA score between the baseline versus after surgery during ON-stimulation deep brain stimulation phase. This phase lasts 1 month, so the evaluation will be performed 01 months after the stimulation is turned on.
Secondary Secondary outcome - change in tremor score using the Fahn Tolosa Marin Scale change in the Fahn Tolosa Marin Scale score between the baseline versus after surgery during ON-stimulation deep brain stimulation phase. This phase lasts 1 month, so the evaluation will be performed 01 months after the stimulation is turned on.
Secondary Secondary outcome - quality of life change in the WHOQOL-bref score between the baseline versus after surgery during ON-stimulation deep brain stimulation phase. This phase lasts 1 month, so the evaluation will be performed 01 months after the stimulation is turned on.

Sponsors