The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, is looking for individuals to participate in clinical studies. Participating in clinical trials allows you to play an active role in research on the nature and causes of many disorders of the brain and nervous system, and to possibly help physician-scientists develop future treatments. The information below is designed to help you quickly learn about actively recruiting research studies for which you or someone you know may be eligible.

Description:

This study (11-N-0211) uses deep brain stimulation (DBS) to treat Parkinson’s disease, dystonia, and essential tremor.  DBS is an approved surgical procedure for these neurological conditions which do not respond well to other treatments. The objective of this research is to study normal human biology and disease pathogenesis (natural history) and to collect physiology and efficacy data related to DBS therapy and motor and cognitive function in the study population.

In this study, researchers will provide DBS surgery for up to 100 people (18 years of age or older) with movement disorders that are FDA-approved indications for DBS, including Parkinson’s disease, dystonia, and essential tremor.

DBS uses a battery-powered device called a neurostimulator (like a pacemaker) that is placed under the skin in the chest.  The stimulator is attached to wires placed into the areas of the brain that affect movement.  Stimulating these areas of the brain helps to block the nerve signals that cause abnormal movements.  The neurostimulator and wires are placed during surgery.  During the surgery, the study investigators will do research procedures that include recording information from wires placed in the brain for surgery, stimulating small areas of the brain through the wires, and having participants do tests of movement, thinking, and reasoning.

Participants in the study will have tests before and after surgery, including brain imaging with MRI and CT scans, tests of thinking and memory, and evaluation of their movement disorder and response to DBS.  These tests are part of standard care for people having DBS surgery.

Participants will have 1-2 outpatient visits before surgery to check eligibility. Those eligible for the study will be admitted to the hospital for surgery for about a week. Participants will return for outpatient visits 1, 2 and 3 months surgery. Each visit will last about two hours. All study visits take place at the NIH Clinical Center in Bethesda, MD. The duration of the study for participants is 3 months. At the end of this surgical study, participants will have the option of continuing post DBS therapy and care at the NIH (for 2 years) under a related protocol, or returning to their own physicians for DBS management and follow-up.

Eligibility Criteria:

INCLUSION CRITERIA: To be eligible for entry into the study, candidates must meet all the following criteria:

  • Be 18 years of age or older.
  • Able to provide informed consent.
  • Have a clinical diagnosis of idiopathic PD, primary dystonia, or ET:
    The diagnosis of idiopathic PD will be based on the UK Brain Bank Criteria, and confirmed by the Movement Disorders Neurologists in the NIH Parkinson Clinic The diagnosis of primary (generalized or segmental), hemidystonia, or cervical dystonia will be confirmed on clinical examination in the NIH Movement Disorders Clinic. The diagnosis of ET will be confirmed on clinical examination in the NIH Movement Disorders Clinic (the diagnosis of ET will be based on bilateral, largely symmetric postural or kinetic tremor involving hands and forearms that is visible and persistent. Additional or isolated tremor in head may be present but there should be the absence of abnormal posturing).
  • History of appropriate response to dopaminergic medication, with at least a 30% improvement in motor UPDRS with L-DOPA by history or in-clinic testing, for the PD patients OR:
  • Patients with tremor-dominant PD that do not respond to dopaminergic therapy and that exhibit a tremor score of at least 2 for tremor severity on at least one side of the body on the motor UPDRS examination.
  • Unsatisfactory clinical response to maximal medical management (with trials of both higher and lower doses of drugs), including: - good benefit from dopaminergic medication but associated with insufficient duration of action or unacceptable side-effects OR - intractable disabling motor fluctuations (severe off periods, dyskinesias, or freezing spells) OR - intractable symptoms of ET or dystonia impacting at least 2 activities of daily living.
  • Agree to undergo DBS if indicated to treat medically refractory movement disorder.

EXCLUSION CRITERIA: Candidates will be excluded if they meet any of the following criteria:

  • Clinically significant medical disease that would increase the risk of developing pre or postoperative complications, including but not limited to uncontrolled systemic hypertension with values above 170/100; active heart disease needing immediate intervention; active respiratory disease needing immediate intervention; uncorrected coagulation abnormalities or need for therapeutic anticoagulation which cannot be interrupted; current or pre-existing life-threatening respiratory disease, such as respiratory failure or ARDS.
  • Cognitive impairment on Full Scale Intelligence Quotient (FSIQ) portion of Wechsler Adult Intelligence test, which would render the participant unable to provide informed consent or to comply with the study procedures (FSIQ less than 70).
  • Evidence of secondary or atypical parkinsonism/dystonia/tremor as suggested by: - History of CVA, exposure to toxins, neuroleptics, or encephalitis - Neurologic signs of upper motor neuron or cerebellar involvement, supranuclear gaze palsy, or orthostatic hypotension. - MR-imaging with evidence indicative of secondary disease such as iron deposits in putamen, tumor, or stroke, which could cause the movement disorder. - Features atypical of idiopathic Parkinson s disease.
  • Dementia as evidenced by formal neuropsychological evaluation and Mattis Dementia Rating Scale-2 (DRS-2) score below 128.
  • Depression or anxiety as evidenced by self-report on the Beck Depression Inventory-2 (score above 20) and Beck Anxiety Inventory, respectively.
  • Unable to undergo MR-imaging because of implanted pacemakers, medication pumps, aneurysm clips, metallic prostheses (including metal pins and rods, heart valves or cochlear implants), shrapnel fragments, permanent eye liner or small metal fragments in the eye that welders and other metal workers may have, or if candidates are uncomfortable in small closed spaces (have claustrophobia), or cannot lie comfortably on their back for up to one hour.
  • Pregnant women.
  • Patients with tremor-dominant PD with Scans Without Evidence of Dopaminergic Effect (SWEDD) will be excluded based on clinical and historic information, including DaT functional imaging obtained during routine clinical evaluation of PD as needed.

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Study Location:

Canada