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

Cerebellar Ataxia Clinical Trial

Official title:

Deep Brain Stimulation on Cerebellar Ataxia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03341416
• Other study ID #: 102178/2015
• Status: Recruiting
• Phase: N/A
• First received: October 30, 2017
• Last updated: November 13, 2017
• Start date: September 1, 2017
• Est. completion date: January 1, 2019

Study information

• Verified date: November 2017
• Source: University of Sao Paulo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: January 1, 2019
• Est. primary completion date: July 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Patients with diagnosis of chronic cerebellar ataxia (> 6 months);

2. Age =18 years;

3. Be able to understand study protocol;

4. Signed, written informed consent (approved by the Institutional Ethics Committee) obtained prior to any study procedure;

5. Refractory symptoms response to first, second and third line pharmacological treatment;

6. Daily living activities impaired because the ataxia;

7. Be able to undergo surgery procedures.

Exclusion Criteria:

1. Abuse of alcohol, drugs

2. Known psychiatric conditions

3. Contraindications to DBS

4. Heart failure or cardiac disease that contraindicates surgery procedures;

5. Pacemaker or other stimulators implanted active;

6. Positive blood ß-HCG test for women;

7. Other medical conditions demand hospitalization; Participation in other clinical studies at the same time;

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia

Intervention

Device:
• deep brain stimulation on stimulation - active
bilateral deep brain stimulation reaching the dentate nucleus turned ON - phase active
• deep brain stimulation off stimulation - sham
bilateral deep brain stimulation reaching the dentate nucleus turned OFF - phase sham

Locations

Country	Name	City	State
Brazil	Rubens Cury	São Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary outcome - change in Scale for the assessment and rating of ataxia - SARA	To evaluate prospectively the effect of DN-DBS in ataxia. The primary outcome is the change between the Scale for the assessment and rating of ataxia (SARA, ranging from 0-40, higher scores mean more severe ataxia) at baseline and after surgery during the active DBS-ON phase	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	To evaluate prospectively the effect of DN-DBS on tremor. The secondary outcome is the change between the Fahn Tolosa Marin Scale (ranging from 0-40, higher scores mean worse tremor) at baseline and after surgery during the active DBS-ON phase	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	To evaluate prospectively the effect of DN-DBS on quality of life. The secondary outcome is the change between the World Health Organization Quality of Life (WHOQOL-bref, 26 items, which measure the following broad domains: physical health, psychological health, social relationships, and environment, higher scores mean better quality of life) at baseline and after surgery during the active DBS-ON phase	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.