Clinical trial NCT03341416: Effects of Deep Brain Stimulation of the Dentate Nucleus on Cerebellar Ataxia
Official title: Deep Brain Stimulation on Cerebellar Ataxia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cerebellar Ataxia
Keywords: cerebellar ataxia
stroke
Spinocerebellar ataxia
deep brain stimulation
dentate nucleus
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2017-11-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: After surgery patients will undergo a first washout period intended to allow their ataxia return to baseline (preoperative levels), thus avoiding post surgery effects bias.

Phase 1: Participants will be randomized to either ON or OFF stimulation. The assigned stimulation will be performed for one week.

Phase 2: Open label phase. All patients are in the ON stimulation condition and will be followed for 6 months.

Duration:

Phase 1 will last from one to 2 months and phase 2 will last six months.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Primary outcome - change in Scale for the assessment and rating of ataxia - SARA
timeFrame: 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 outcomes:
measure: Secondary outcome - change in tremor score using the Fahn Tolosa Marin Scale
timeFrame: 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.
measure: Secondary outcome - quality of life
timeFrame: 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.
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Rubens Cury
state: SP
Study officials:
References: