Combined Deep Brain Stimulation for Parkinson's Disease

Parkinson Disease Clinical Trial

Official title: Pilot Study of Bilateral Pedunculo-Pontine Nucleus (PPN) Deep Brain Stimulation for Patients With Parkinson Disease (PD) Who Have Persistent Gait Disturbance, Despite Bilateral Subthalamic Nucleus (STN) Deep Brain Stimulation

Status Withdrawn

Clinical Trial 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.

Clinical Trial Description

OBJECTIVE:

1. Determine if bilateral Pedunculo-Pontine Nucleus (PPN) Deep Brain Stimulation (DBS) will improve gait and balance problems in Parkinson Disease (PD) patients whose other disease features have responded to bilateral subthalamic nucleus (STN) DBS and medications

2. Determine if bilateral PPN DBS will improve swallowing function in Parkinson Disease patients treated with bilateral STN DBS and medication

3. Obtain electrophysiological data related to PPN

4. Obtain data related to the physiological relationship of the STN and PPN

STUDY POPULATION:

Three (3) subjects with clinically diagnosed PD who have undergone bilateral STN DBS at least one year prior to enrollment, who continue to have gait and balance disturbance.

DESIGN:

Pilot study of 3 patients with clinically diagnosed PD who have undergone bilateral STN DBS at least one year prior to enrollment. Baseline evaluation will include neurologic clinical evaluation, postural and gait physiologic and clinical assessment, brain imaging, and video swallow evaluation. The patients will undergo the surgical procedure (bilateral PPN DBS implant) in the Clinical Center (CC). Electrode recordings will be obtained from the implant site within the first week post-operatively from an externalized lead, then the second surgical stage (pulse generator implant) will take place, also in the Clinical Center. The patients will undergo programming to optimal parameters and appropriate follow-up, and the outcome measures will be assessed at 1 week and 1, 3, 6 and 12 months post-surgery. Recruitment will be staggered and at least 4 weeks will be required between different patients beginning the study. Recruitment will be halted if major unexpected side-effects occur causing concern about the welfare of patients.

This study is to serve as the basis for an extended, larger study, which would be properly powered to answer the clinical research questions. The efficacy criterion for translation into a larger study will be 30% improvement in the primary outcome in 2 out of the 3 patients. In addition, we will obtain valuable and for the most part novel data regarding the electrophysiologic properties of the PPN and the complex interactions between basal ganglia (BG) components in the parkinsonian state and the response to DBS. The data obtained in this study will inform the design, selection and treatment paradigms in future larger studies.

OUTCOME MEASURES:

Primary:

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

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

Secondary:

• Change in time needed to complete the TUG study at 1, 3 and 12 months post-surgery on stimulation

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

• Parkinson's Disease Questionnaire (PDQ 31) quality of life questionnaire at 6 months

• Change in static and dynamic posturography outcome parameters at 1, 3, 6 and 12 months on stimulation

• Number of adverse events during the follow-up period

• Change in timed and non-timed variables of swallowing function at 6 months

• Recorded physiologic function of PPN with STN stimulator off and on at rest and during gait

• Changes in the patient global impression of change at 1, 3, 6, and 12 months. All the outcome measures are assessed on best medical therapy.. ;

Related Conditions & MeSH terms

• Parkinson Disease

• NCT number: NCT01485276
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: November 8, 2011
• Completion date: July 30, 2014