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Trial record 1 of 184 for:    "autosomal recessive cerebellar ataxia type 1" OR "Cerebellar Ataxia"
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Effects of Deep Brain Stimulation of the Dentate Nucleus on Cerebellar Ataxia

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ClinicalTrials.gov Identifier: NCT03341416
Recruitment Status : Recruiting
First Posted : November 14, 2017
Last Update Posted : November 17, 2017
Sponsor:
Information provided by (Responsible Party):
Rubens Gisbert Cury, University of Sao Paulo General Hospital

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.

Condition or disease Intervention/treatment Phase
Cerebellar Ataxia Device: deep brain stimulation on stimulation - active Device: deep brain stimulation off stimulation - sham Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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.

Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Deep Brain Stimulation on Cerebellar Ataxia
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : July 1, 2018
Estimated Study Completion Date : January 1, 2019


Arm Intervention/treatment
Experimental: Device - deep brain stimulation ON

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

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

Sham Comparator: Device - deep brain stimulation Sham

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

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




Primary Outcome Measures :
  1. Primary outcome - change in Scale for the assessment and rating of ataxia - SARA [ Time Frame: 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. ]
    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


Secondary Outcome Measures :
  1. Secondary outcome - change in tremor score using the Fahn Tolosa Marin Scale [ Time Frame: 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. ]
    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

  2. Secondary outcome - quality of life [ Time Frame: 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. ]
    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



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03341416


Locations
Brazil
Rubens Cury Recruiting
São Paulo, SP, Brazil
Contact: Rubens Cury, MD PhD    5511972838184    rubens_cury@usp.br   
Contact: carina franca, MD    1131590293      
Sponsors and Collaborators
University of Sao Paulo General Hospital

Responsible Party: Rubens Gisbert Cury, Medical Assistant, Movement Disorders Unit. Principal Investigator. MD, PhD, University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT03341416     History of Changes
Other Study ID Numbers: 102178/2015
First Posted: November 14, 2017    Key Record Dates
Last Update Posted: November 17, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rubens Gisbert Cury, University of Sao Paulo General Hospital:
cerebellar ataxia
stroke
Spinocerebellar ataxia
deep brain stimulation
dentate nucleus

Additional relevant MeSH terms:
Ataxia
Cerebellar Ataxia
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases