Cerebellar DBS in SCA1 and SCA3 Study
Deep Brain Stimulation of the Deep Cerebellar Nuclei in Subjects With Spinocerebellar Ataxia: A Safety and Feasibility Study
The purpose of this study is to evaluate the safety and feasibility of deep brain stimulation (DBS) in the deep cerebellar nuclei (DCN) in patients with Spinocerebellar Ataxia (SCA) types 1 and 3.
Primary Objective: The incidence and nature of treatment-related adverse events across the entire study, including serious treatment-related adverse events such as intracerebral hemorrhage, infection, and serious or unanticipated adverse device effects (SADEs and UADEs).
Secondary/Exploratory Objectives:
- Evaluation of the effect of Dentate Nucleus (DN) - Deep Brain Stimulation (DBS). Ataxia severity will be quantified using the Scale of Assessment and Rating of Ataxia (SARA), Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia), and kinematics.
- To characterize electrophysiological activity across the cerebellothalamocorticomuscular (CTCM) network at rest and during motor behaviors.
- To examine how DN-DBS modulates oscillatory activity and coupling across the CTCM circuit in relation to improvements in controlling ataxia.
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
People with spinocerebellar ataxia (SCA) face progressively disabling symptoms such as poor balance, frequent falls, and a loss of muscle control. Currently, there are no approved treatments for these symptoms.
Developing medications to treat SCA is incredibly difficult because the brain's movement center-the cerebellum-has complex, damaged wiring that varies between patients. However, all signals from this complex brain region flow through a single exit point called the deep cerebellar nuclei (DCN). This makes the DCN (specifically, the dentate nucleus or DN) a perfect target for brain stimulation. Over the past five years, animal studies have shown that using a device to stimulate this area (called deep brain stimulation, or DBS) can significantly improve movement control. Recently, a small study showed promising early results in humans, particularly in two patients with SCA type 3.
To translate these findings into a standard treatment that has the potential to improve patients' lives, the investigators must first determine whether this is feasible and safe. The investigators will also need to see if this treatment works for different types of SCA, since cerebellar damage varies from person to person. Therefore, the aim of this study is to test and safety, feasibility, and early effectiveness of DBS on both sides of the brain in 12 people with SCA types 1 and 3. During the study, the investigators will use temporary external wires and a brain-recording device to listen to the brain's signals. By matching these signals with standard brain wave tests (EEGs), the investigators will hopefully understand exactly how this stimulation fixes the brain's movement network.
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Natasha Desai
- Telefonní číslo: 347-882-4315
- E-mail: nd2528@cumc.columbia.edu
Studijní záloha kontaktů
- Jméno: Gordon Baltuch, MD, PhD
- E-mail: gb2774@cumc.columbia.edu
Studijní místa
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New York
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New York, New York, Spojené státy, 10032
- Columbia University Irving Medical Center
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Kontakt:
- Natasha Desai
- Telefonní číslo: 347-882-4315
- E-mail: nd2528@cumc.columbia.edu
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Kontakt:
- Nadia Amokrane
- Telefonní číslo: 347-882-4315
- E-mail: na2855@cumc.columbia.edu
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Vrchní vyšetřovatel:
- Gordon Baltuch, MD
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Dílčí vyšetřovatel:
- Sheng-Han Kuo, MD
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Ohio
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Cleveland, Ohio, Spojené státy, 44195
- Cleveland Clinic
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Kontakt:
- Jeffrey Negrey
- Telefonní číslo: 216-316-6896
- E-mail: negreyj2@ccf.org
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Vrchní vyšetřovatel:
- Andre Machado, MD
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Dílčí vyšetřovatel:
- Kenneth Baker, PhD
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
Přijímá zdravé dobrovolníky
Popis
Inclusion Criteria:
- Subject is aged >= 18 years and =< 60 years.
- Subject has moderate ataxia severity, as demonstrated by a Scale for Ataxia Rating and Assessment (SARA) score >= 11.
- Subject has genetic confirmation of pathological repeat expansions in ATXN1 (for SCA1, repeat size >= 40) and ATXN3 (for SCA3, repeat size >= 56).
- Subject has been on a stable and optimized standard of care (SoC) regimen for at least 3 months prior to Screening (including physical therapy) and continues to exhibit signs of cerebellar ataxia.
- Subject has a minimum 6th grade reading level, as determined by the Rapid Estimate of Adult Literacy in Medicine (REALM) scale.
- Subject is able and willing to give informed consent and attend all study visits.
- Subject is available for all follow-up visits during the length of the study.
Exclusion Criteria:
- Subject is unable to provide informed consent.
- Subject has presence of overt tremor, dystonia, and/or parkinsonism, which are atypical features and could be suggestive of prominent extra-cerebellar circuit involvement that may not respond well to cerebellar DBS.
- Subject is wheelchair dependent and may be too progressed to complete gait assessments.
- Subject is unable to stop anticoagulation or platelet anti-aggregation therapy for study procedures.
- Subject has a Montreal Cognitive Assessment (MoCA) score =< 24.
- Subject has a diagnosis of epilepsy.
- Subject has a major active psychiatric illness that may interfere with the study, such as psychiatric disorders or severe personality disorders.
- Subject has an untreated or inadequately treated major depressive episode.
- Subject is pregnant, lactating, or planning to become pregnant during the study.
- For women of childbearing potential, subject is unable or unwilling to use accepted contraception methods.
- Subject is unable to communicate with investigators or staff.
- Subject has contraindications to DN DBS, including significant small vessel ischemic disease, vertebrobasilar vascular disease, and/or any other structural abnormalities of the cerebellum, cerebellar peduncles, and brain stem that would preclude safe placement of the DBS leads.
- Subject has contraindications to magnetic resonance (MR) imaging, e.g., weight incompatible with scanner, implanted metallic devices or electrical devices (pacemaker, defibrillator, spinal cord stimulator), or intolerance to MRI contrast agents.
- Subject is enrolled in another device, biologic or pharmaceutical study within 30 days of consent in the current study (i.e., patients cannot be enrolled if participation in another study was not completed at least 30 days prior to consent).
- Subject has evidence of behavior(s) consistent with alcohol or substance abuse/dependence within the preceding 6 months, as outlined by the DSM-V criteria.
- Subject has a condition that, in the opinion of the investigator, would significantly increase the risk for interference with study compliance, safety, or outcome.
- Subject is at risk for suicide, defined by a total score >= 3 on the Columbia Suicide Severity Rating Scale (C-SSRS).
- Patients who are not able to read, speak and/or understand English.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: DBS Intervention
Participants will undergo surgical implantation of the DBS leads, followed by a second surgery to implant a pulse generator (IPG) which generates electricity.
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The UG3NS140720 Deep Brain Stimulation System is primarily comprised of components from the Medtronic Percept™ system, which is approved in the U.S. by the FDA for unilateral or bilateral stimulation of the ventral intermediate nucleus (VIM) of the thalamus as adjunctive therapy for ET, cerebellar outflow tremor, and MS-related tremor. This system is also approved to be used on patients with neurologic disorders such as Parkinson's disease, dystonia, or epilepsy. The FDA has not approved any DBS system for the stimulation of the Deep Cerebellar Nuclei (DCN) for this patient population. Deep brain stimulation (DBS) utilizes surgically implanted electrodes and a neurostimulator to deliver electrical energy to specific targeted structures deep within either one or both hemispheres of the brain.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Incidence of treatment-related adverse events
Časové okno: Up to 72 months
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To further understand the safety and optimize a novel therapeutic target to achieve ataxia control for individuals with SCA.
The adverse events will be evaluated and tallied if they met the criteria as Serious Adverse Events (SAE), Serious Adverse Device Effects (SADE), and Unanticipated (Serious) Adverse Device Effects (UADE).
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Up to 72 months
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Mean Scale for Assessing and Rating of Ataxia (SARA) Score
Časové okno: Baseline, Month 11
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To characterize the effect of DN-DBS on disease-related impairments, the study will measure ataxia severity as assessed by the Scale for Assessing and Rating of Ataxia (SARA).
SARA is a clinical scale that includes 8 different domains of neurological exams, including gait, stance, sitting, speech, and hand dexterity.
The total amount of points on SARA ranges from 0 (no ataxia) to 40 (most severe ataxia).
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Baseline, Month 11
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Mean Patient-Reported Outcome Measures - Ataxia (PROM-Ataxia) Scale Score
Časové okno: Baseline, Month 11
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To characterize the effect of DN DBS on ataxia severity and related cognitive and emotional symptoms in SCA, the study will utilize the Patient-Reported Outcome Measures - Ataxia (PROM-Ataxia) scale.
PROM-Ataxia is a 3-domain, 70-item questionnaire which assesses the impact of cerebellar dysfunction on physical abilities, activities of daily living, and cognitive-emotional challenges.
The maximum severity score on PROM-Ataxia is 280, where all 70 questions are scored on a 0-4 Likert scale.
0 represents never and 4 represents always.
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Baseline, Month 11
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Mean Cerebellar Cognitive Affective Syndrome Scale (CCAS) Score
Časové okno: Baseline, Month 11
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SCA patients may have cognitive impairment, presumed to come from the dysfunctional cerebellum.
Therefore, cognition status will be measured by the Cerebellar Cognitive Affective Syndrome Scale (CCAS).
The CCAS evaluates multiple cognitive domains such as executive function, attention, memory, language, visual-spatial skills, abstract reasoning, and neuropsychiatric features.
The total possible score is 120 points; the Pass / Fail measure provides a maximum fail score of 10 (i.e., 10 failed tests).
A fail score of 0 is normal.
In a patient with cerebellar disease, a fail score of 1 indicates Possible CCAS, a fail score of 2 indicates Probable CCAS, and a fail score of 3 or more indicates Definite CCAS.
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Baseline, Month 11
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Mean Patient Health Questionnaire (PHQ-9) Score
Časové okno: Baseline, Month 11
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To assess depression symptoms, the Patient Health Questionnaire assessment will be used.
The PHQ is a 9-item patient-reported assessment which asks how often a patient has experienced a symptom in the prior 2 weeks.
Responses range from "0" (Not at all) to "3" (nearly every day).
Scores range from 0 to 27, with total scores over 10 indicating a presence of depression.
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Baseline, Month 11
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Mean Generalized Anxiety Disorder (GAD) Scale Score
Časové okno: Baseline, Month 11
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To assess anxiety symptoms, the GAD scale will be used.
The Generalized Anxiety Disorder (GAD) scale is a 7-item patient-reported assessment which assesses how often a patient has experienced a symptom of anxiety in the last 2 weeks.
To assess depression symptoms, the Patient Health Questionnaire assessment will be used.
Responses range from "0" (Not at all) to "3" (nearly every day).
Scores range from 0 to 21, with total scores over 10 indicating a presence of anxiety.
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Baseline, Month 11
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Mean Patient Global Impression (PGI) Score
Časové okno: Baseline, Month 11
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The Patient Global Impression (PGI) scores are single-item patient-reported assessments.
This study will use the severity (PGI-S) and change (PGI-C) scores.
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Baseline, Month 11
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Mean Gait Measure of Ataxia
Časové okno: Baseline, Month 11
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Kinematic measures of ataxia will be measured by 6 wearable sensors from the APDM Mobility Lab System.
The system has recently been validated to track cerebellar ataxia severity in SCA patients.
SCA patients have increased postural sway, increased toe-out angle variability, and increased double-support time variability.
APDM sensors will also be used to study different gait cycles and finger-to-target movements as indicators for gait and hand ataxia, respectively.
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Baseline, Month 11
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Mean Postural Kinematic Measure of Ataxia
Časové okno: Baseline, Month 11
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Kinematic measures of ataxia will be measured by 6 wearable sensors from the APDM Mobility Lab System.
The system has recently been validated to track cerebellar ataxia severity in SCA patients.
SCA patients have increased postural sway, increased toe-out angle variability, and increased double-support time variability.
APDM sensors will also be used to study different gait cycles and finger-to-target movements as indicators for gait and hand ataxia, respectively.
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Baseline, Month 11
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Mean EQ-5D-3L Score
Časové okno: Baseline, Month 11
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The EQ-5D-3L is a self-assessed, health related, quality of life questionnaire.
The scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
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Baseline, Month 11
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Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Number of evaluable recordings completed by participants
Časové okno: From Implant to End of Study (Approximately 11 Months)
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EEG, EMG, and LFP recordings will be collected at rest and during ataxia-eliciting behaviors at specified study visits to characterize activity, as well as assess how DN-DBS modulates oscillatory activity and coupling, across the cerebellothalamocorticomuscular (CTCM) network.
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From Implant to End of Study (Approximately 11 Months)
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Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Gordon Baltuch, MD, CUIMC
- Ředitel studie: Sheng-Han Kuo, MD, CUIMC
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další identifikační čísla studie
- ACYY0046
- 1UG3NS140720-01 (Grant/smlouva NIH USA)
Plán pro data jednotlivých účastníků (IPD)
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