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Thalamic Deep Brain Stimulation for Secondary Dystonia in Children and Young Adults (DBSVop)

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ClinicalTrials.gov Identifier: NCT03078816
Recruitment Status : Recruiting
First Posted : March 13, 2017
Last Update Posted : May 2, 2017
Sponsor:
Information provided by (Responsible Party):
Amy Viehoever, University of California, San Francisco

Brief Summary:

Dystonia is a movement disorder seen in both children and adults that is characterized by "sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both." Secondary dystonia is far more common in pediatric populations than primary dystonia, and far more recalcitrant to standard pharmacologic and surgical treatments including Deep Brain Stimulation (DBS). There exists a large unmet need to develop new therapeutics, treatment strategies, and outcome measures for pediatric secondary dystonia.

The investigators are proposing to investigate the ventralis oralis posterior nucleus (Vop) of the thalamus as a new target for DBS in secondary dystonia. Prior to the development of DBS, the main surgical treatment of dystonia was thalamotomy. Although there were many different targets in the thalamus, often done in staged procedures, the most common and successful targeted nuclei was the Vop, which is traditionally thought to be the pallidal receiving area. Previous lesioning of Vop produced improvements in dystonia but intolerable side effects, especially when implanted bilaterally. However, given that secondary dystonia patients were often reported to have superior results to primary dystonia it is reasonable to believe that if the side effects can be modulated, that targeting of the Vop nucleus with DBS could be a viable alternative to Globus Pallidus interna (GPi). Given that Deep Brain Stimulation is a treatment that is inherently adjustable, it is conceivable that settings on the Deep Brain Stimulation could be adjusted to allow for clinical benefit with minimal side effects. Indeed, there have been several scattered successful case reports attesting to this possibility.


Condition or disease Intervention/treatment Phase
Dystonia Device: Activa PC Primary Cell Neurostimulator - (Model 37601) Device: Activa RC Rechargeable Neurostimulator - (Model 37612) Device: Activa SC Single Cell Neurostimulator (Models 37602/37603) Device: DBS Lead - (Model 3387 Device: DBS Extension - (Models 37085/6) Device: Patient Programmer - (Model 37642) Device: Test Stimulator - (Model 3625) Device: N'Vision Clinician Programmer - (Model 8840) Device: N'Vision Software Application Card - (Model 8870) Phase 1

Detailed Description:

Dystonia is a movement disorder seen in both children and adults that is characterized by "sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both." Secondary dystonia has evolved to refer to dystonia resulting from damage to the nervous system or degenerative disease processes. While primary dystonia is generally thought to arise from genetic causes, secondary dystonias have a variety of causes including perinatal injuries (cerebral palsy), central nervous system infections, traumatic brain injuries, and many different metabolic, neurodegenerative, and mitochondrial conditions. Secondary dystonia is far more common in pediatric populations than primary dystonia, and far more recalcitrant to standard pharmacologic and surgical treatments including Deep Brain Stimulation. Given that most treatments for dystonia are developed for primary dystonia and then applied to secondary dystonia, it is not surprising that this effectiveness gap exists. Thus, there exists a large unmet need to develop new therapeutics, treatment strategies, and outcome measures for pediatric secondary dystonia.

Deep Brain Stimulation (DBS) is one such therapeutic intervention that has potential to improve secondary dystonia. DBS is a surgical treatment for several different movement disorders that evolved from functional stereotactic neurosurgery techniques initially used to lesion specific deep brain structures. While Essential Tremor and Idiopathic Parkinson's Disease have predictable and consistent response rates to DBS in carefully selected patients, response rates of dystonia have been much more inconsistent. One predictor of success has been the presence of DYT-1 mutation, the most common known genetic cause of primary dystonia. Success rates in DYT-1 dystonia are consistently high with reductions in dystonia typically greater than 80%. However, the results in secondary dystonia have been much more modest and inconsistent. A recent meta-analysis found that on average, dystonia symptoms as measured by common rating scales improve 23% following DBS for dystonic cerebral palsy (the most common cause of secondary dystonia), however there are frequent cases of non-responders. Additionally, there have been very few examination, radiological or laboratory predictors of good response to DBS, except for genetic confirmation of DYT-119. However, across both primary and secondary dystonia, younger age at the time of surgery (less than 21 years old) and shorter duration of symptoms (less than 15 years) have been shown to be the most likely predictive factors for a good postoperative outcome. This has led many to suggest that DBS should be offered earlier in the course of intractable dystonia, prior to the development of permanent complications such as orthopedic contractures. Thus, we are setting an upper age limit of 25 to account for the concern that earlier implantation leads to improved outcomes. The lower age limit of 7 reflects the fact that the current humanitarian exemption for DBS for dystonia currently goes down to age 7. Thus, there exists a need to both improve patient selection as well as application of DBS for secondary dystonia in children.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Thalamic Deep Brain Stimulation for Secondary Dystonia in Children and Young Adults
Actual Study Start Date : March 3, 2017
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dystonia
U.S. FDA Resources

Arm Intervention/treatment
Experimental: DBS active

All participants will be enrolled in DBS placement and active stimulation. The following components will be used:

  • Activa PC Primary Cell Neurostimulator - (Model 37601)
  • Activa RC Rechargeable Neurostimulator - (Model 37612)
  • Activa SC Single Cell Neurostimulator (Models 37602 and 37603)
  • DBS Lead - (Model 3387)
  • DBS Extension - (Models 37085/6)
  • Patient Programmer - (Model 37642)
  • Test Stimulator - (Model 3625)
  • N'Vision Clinician Programmer - (Model 8840)
  • N'Vision Software Application Card - (Model 8870)
Device: Activa PC Primary Cell Neurostimulator - (Model 37601)
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Device: Activa RC Rechargeable Neurostimulator - (Model 37612)
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Device: Activa SC Single Cell Neurostimulator (Models 37602/37603)
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Device: DBS Lead - (Model 3387
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Device: DBS Extension - (Models 37085/6)
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Device: Patient Programmer - (Model 37642)
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Device: Test Stimulator - (Model 3625)
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Device: N'Vision Clinician Programmer - (Model 8840)
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.
Device: N'Vision Software Application Card - (Model 8870)
Deep Brain Stimulator system will be implanted using standard neurosurgical techniques. The device will deliver constant stimulation to the thalamus using settings programmed by study team.



Primary Outcome Measures :
  1. Adverse Events (AEs) and serious adverse events (SAEs) [ Time Frame: Collected at every study visit between baseline and 12 months post operatively. ]
    This will include the relationship to the study procedure and/or device, as determined by the Investigator.

  2. Burke-Fahn-Marsden Dystonia Rating Scale [ Time Frame: Change from baseline to 12 months postoperatively ]
    Rating scale that measures movement and disability related to dystonia

  3. Pediatric Quality of Life Inventory (PedsQL) [ Time Frame: Change from baseline to 12 months postoperatively ]
    Quality of life measure

  4. Barry Albright Dystonia Rating Scale [ Time Frame: Change from baseline to 12 months postoperatively ]
    Severity scale for secondary dystonia


Secondary Outcome Measures :
  1. Modified Ashworth Scale [ Time Frame: Change from baseline to 12 months postoperatively ]
    Measure of spasticity

  2. Pediatric Evaluation of Disability Inventory Computer Administrated Test [ Time Frame: Change from baseline to 12 months postoperatively ]
    Measure of mobility

  3. Gross Motor Function Measure (GMFM) [ Time Frame: Change from baseline to 12 months postoperatively ]
    Measure of mobility

  4. Diadochokinetic Syllable Rates [ Time Frame: Change from baseline to 12 months postoperatively ]
    Articulation

  5. Kaufman Brief Intelligence Test, 2nd Edition [ Time Frame: Change from baseline to 12 months postoperatively ]
    Verbal and nonverbal IQ

  6. Children's Memory Scale [ Time Frame: Change from baseline to 12 months postoperatively ]
    Will include the following subtests: Memory for Faces, Dot Locations, and Digit Span

  7. Behavioral Assessment System, 3rd Edition: Self report of personality [ Time Frame: Change from baseline to 12 months postoperatively ]
    Mood and behavior assessment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   7 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Ability to give informed consent or assent for the study
  2. Dystonia symptoms that are sufficiently severe, in spite of best medical therapy, to warrant surgical implantation of deep brain stimulators according to standard clinical criteria
  3. Age 7-25
  4. Stable doses of anti-dystonia medications (such as levodopa, baclofen, or diazepam) for at least 30 days prior to baseline assessment
  5. If patient receives botulinum toxin injections, patient should be on a stable injection regimen
  6. Intact thalamic anatomy as determined by standard clinical MRI

Exclusion Criteria:

  1. Pregnancy or breast feeding
  2. Major comorbidity increasing the risk of surgery (severe hypertension, severe diabetes, or need for chronic anticoagulation other than aspirin)
  3. Inability to comply with study follow-up visits
  4. Any prior intracranial surgery
  5. Uncontrolled epilepsy
  6. Immunocompromised
  7. Has an active infection
  8. Requires diathermy, electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) to treat a chronic condition
  9. Has an existing implanted neurostimulator or cardiac pacemaker.
  10. Dystonia caused by known genetic mutation in any DYT genes

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): NCT03078816


Contacts
Contact: Amy R Viehoever, MD, PhD 415-353-2311 amy.viehoever@ucsf.edu
Contact: Kristen A Dodenhoff 415-353-1555 kristen.dodenhoff@ucsf.edu

Locations
United States, California
University of California San Francisco Hospital Recruiting
San Francisco, California, United States, 94158
Contact: Amy R Viehoever, MD PhD    415-353-2311    Amy.Viehoever@ucsf.edu   
Contact: Kristen A Dodenhoff    415-353-1555    kristen.dodenhoff@ucsf.edu   
Sub-Investigator: Carly Demopoulos, PhD         
Sub-Investigator: Paul S Larson, MD         
Sub-Investigator: Jill L Ostrem, MD         
Sub-Investigator: Caroline Racine, MD         
Sub-Investigator: Marta San Luciano-Palenzuela, MD         
Sub-Investigator: Philip A Starr, MD         
Sub-Investigator: Monica M Volz, RN         
Sub-Investigator: Sarah Wang, MD         
Sub-Investigator: Christa Watson, PsyD         
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Amy R Viehoever, MD, PhD University of California, San Francisco

Additional Information:
Publications of Results:

Responsible Party: Amy Viehoever, Assistant Adjunct Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03078816     History of Changes
Other Study ID Numbers: 123822A
First Posted: March 13, 2017    Key Record Dates
Last Update Posted: May 2, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Dystonia
Dystonic Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Movement Disorders
Central Nervous System Diseases