Combined Deep Brain Stimulation for Parkinson's Disease

NCT01485276 | Withdrawn Phase 1

• 2 other identifiers: 12001212-N-0012
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: \- Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is an approved treatment for Parkinson s disease. It stimulates a part of the brain that helps control symptoms like tremor, stiffness, and slow movements. However, many people continue to have unsteadiness and slowness while walking, trouble swallowing, and speech problems even with STN DBS. Another type of DBS focuses on a part of the brain called the pedunculopontine nucleus (PPN). PPN DBS has improved walking in some people with Parkinson's disease. Researchers want to see if combining the two types of DBS may help control symptoms better than STN DBS alone. Objectives:

• To see if PPN DBS can help walking, balance, speaking, and swallowing in those who already have STN DBS.
• To study how the DBS combination affects brain function. Eligibility: \- Individuals with Parkinson s disease who had STN DBS surgery at least 1 year ago, but still have difficulty walking, swallowing, and speaking. Design:
• Participants will be screened with a physical exam and medical history. They will also have neurological tests and other tests to measure Parkinson s disease symptoms.
• This study requires eight visits over 1 year. One of the visits will be a 9- to 10-day admission to the NIH Clinical Center for DBS surgery.
• Participants will have PPN DBS surgery. The surgery will be done in two steps. In the first step, the leads will be placed in the brain. In the second step, 1 week later, the stimulator device will be placed in the chest or abdomen.
• One month after the surgery, participants will have a study visit to program the PPN DBS device to find settings that will improve walking and balance.
• Participants will have study visits 2, 3, 6, and 12 months after surgery. Each visit will be used to check the stimulators and make any adjustments needed to try to improve walking and balance or to lessen side effects. Participants will have tests of walking and balance, speech, and swallowing. Some tests will be done with different combinations of the stimulators on or off to see the effects of each set of stimulators.

Conditions

Parkinson Disease

Keywords

Parkinson's Disease; Deep Brain Stimulation; Gait; Electrophysiology; Parkinson Disease; PD

Outcome Measures

Primary Outcomes (1)

• Change in the amount of time needed to complete a standardized timed up and go (TUG) study at 6 months post-surgery on stimulation

Secondary Outcomes (5)

• TUG study at 1, 3 and 12 months post-surgery.

• UPDRS III score and UPDRS III points 27-30 at 1, 3, 6 and 12 months

• PDQ 31 questionnaire at 6 months

• Swallowing function at 6 moths

• Static and dynamic posturography parameters at 1, 3, 6 and 12 months on stimulation.

Interventions

DBS Surgery PROCEDURE

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• i. Greater than 22 years of age
• ii. Successful bilateral STN DBS implants for at least 1 year
• iii. At least 30% improvement in the motor UPDRS following STN therapy, by history and record review
• iv. Improved UPDRS and self assessment questionnaire following STN DBS by at least 20%, by history and record review.
• v. Good STN DBS placement assessed with imaging (CT scan, MRI or fused CT-MRI imaging)
• vii. Persistent gait disturbance as ascertained by abnormal performance on the time-up-and-go test compared to age-matched controls as well as preoperative evaluation with posturography and quantitative gait assessment (values compared to normal age-matched controls) at least 30% difference from age-matched controls on either measure.
• vii. Persistent speech and swallowing problems as measured by a minimum score of I in items 5 and 7 of the UPDRS
• viii. Evaluation by an independent movement disorders specialist who will confirm gait disturbance in the presence of STN stimulation.

You may not qualify if:

• i. Pregnant or nursing women
• ii. Cognitively impaired subjects as determined by pre-operative neuropsychology evaluation, including Mattis Dementia Rating Scale (DRS). Patients scoring below 70 on the Mattis DRS will be excluded.
• iii. Depressed subjects as determined by the neuropsychology screen, including Beck Depression Inventory. Patients scoring above 20 on the Beck inventory will be excluded.
• iv. Patients with uncontrolled co-existing medical conditions: uncontrolled systemic hypertension with values above 170/100; heart disease needing intervention; respiratory disease needing intervention; uncorrected coagulation abnormalities or need for therapeutic anticoagulation which cannot be interrupted; any condition that would render the patient unable to safely cooperate with the study tests as judged by the screening physician.
• v. Patients with metal objects in their body that are not MRI compatible, excluding the previous STN DBS hardware
• vi. Patients who have a history of seizures, require repeated magnetic resonance imaging (MRI) scans or have had a cranial neurosurgical procedure since receiving an STN implant.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Related Publications (3)

• Rodriguez-Oroz MC, Obeso JA, Lang AE, Houeto JL, Pollak P, Rehncrona S, Kulisevsky J, Albanese A, Volkmann J, Hariz MI, Quinn NP, Speelman JD, Guridi J, Zamarbide I, Gironell A, Molet J, Pascual-Sedano B, Pidoux B, Bonnet AM, Agid Y, Xie J, Benabid AL, Lozano AM, Saint-Cyr J, Romito L, Contarino MF, Scerrati M, Fraix V, Van Blercom N. Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up. Brain. 2005 Oct;128(Pt 10):2240-9. doi: 10.1093/brain/awh571. Epub 2005 Jun 23.

  PMID: 15975946 BACKGROUND

• Benabid AL, Pollak P, Gross C, Hoffmann D, Benazzouz A, Gao DM, Laurent A, Gentil M, Perret J. Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease. Stereotact Funct Neurosurg. 1994;62(1-4):76-84. doi: 10.1159/000098600.

  PMID: 7631092 BACKGROUND

• Kleiner-Fisman G, Fisman DN, Sime E, Saint-Cyr JA, Lozano AM, Lang AE. Long-term follow up of bilateral deep brain stimulation of the subthalamic nucleus in patients with advanced Parkinson disease. J Neurosurg. 2003 Sep;99(3):489-95. doi: 10.3171/jns.2003.99.3.0489.

  PMID: 12959435 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Mark Hallett, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2011
• First Posted: December 5, 2011
• Study Start: November 8, 2011
• Study Completion: July 30, 2014
• Last Updated: November 15, 2019

Record last verified: 2014-07-30