Parkinson DiseasePhase 1/2NCT01485276
Combined Deep Brain Stimulation for Parkinson's Disease
A Phase 1/2 study testing DBS Surgery in people with Parkinson Disease, run by National Institute of Neurological Disorders and Stroke (NINDS).
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. Read more about this study
- Who is it for?
- Ages 22 years and older
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- DBS Surgery
- Type of treatment
- Surgery or procedure
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 8 Nov 2011to 30 Jul 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Pregnant or nursing women
- 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.
- Depressed subjects as determined by the neuropsychology screen, including Beck Depression Inventory. Patients scoring above 20 on the Beck inventory will be excluded.
- 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.
- Patients with metal objects in their body that are not MRI compatible, excluding the previous STN DBS hardware
- 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.
About this study
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
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.
Read more
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.
Read the detailed description
OBJECTIVE:
- 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
- Determine if bilateral PPN DBS will improve swallowing function in Parkinson Disease patients treated with bilateral STN DBS and medication
- Obtain electrophysiological data related to PPN
- 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..
- Conditions
- Parkinson Disease
- Being tested
- DBS Surgery
- Keywords
- Parkinson's Disease, Deep Brain Stimulation, Gait, Electrophysiology, Parkinson Disease, PD
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DBS SurgeryProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2011 (estimated)
- Study start8 Nov 2011
- Study completion30 Jul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mark Hallett, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01485276
- Sponsor's protocol ID
- 120012
- Other IDs
- 12-N-0012
- Status last verified
- 30 Jul 2014
- First submitted
- 2 Dec 2011
- Last updated
- 15 Nov 2019
- Results posted
- No
Publications
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.
PubMed 15975946Benabid 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.
PubMed 7631092Kleiner-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.
PubMed 12959435
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01485276
- Acronym / sponsor ID
- 120012
- Conditions
- Parkinson Disease
- Keywords
- Parkinson's Disease, Deep Brain Stimulation, Gait, Electrophysiology, Parkinson Disease, PD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 8 Nov 2011
- Study completion
- 30 Jul 2014 (actual)
- First posted
- 5 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVE:
- 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
- Determine if bilateral PPN DBS will improve swallowing function in Parkinson Disease patients treated with bilateral STN DBS and medication
- Obtain electrophysiological data related to PPN
- 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..
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 22 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (6 listed)
- Pregnant or nursing women
- 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.
- Depressed subjects as determined by the neuropsychology screen, including Beck Depression Inventory. Patients scoring above 20 on the Beck inventory will be excluded.
- 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.
- Patients with metal objects in their body that are not MRI compatible, excluding the previous STN DBS hardware
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DBS Surgery | Procedure or surgery | – |
Primary outcome
Change in the amount of time needed to complete a standardized timed up and go (TUG) study at 6 months post-surgery on stimulation
5 secondary outcomes
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2019.
- Background: PubMed 15975946Rodriguez-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.
- Background: PubMed 7631092Benabid 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.
- Background: PubMed 12959435Kleiner-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Hallett, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DBS Surgery in people with Parkinson Disease, run by National Institute of Neurological Disorders and Stroke (NINDS).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the amount of time needed to complete a standardized timed up and go (TUG) study at 6 months post-surgery on stimulation. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01485276, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2019; AzTrials last refreshed its copy on 6 Nov 2026.