Parkinson's Disease
Conditions
Keywords
Parkinson's disease, levo-dopa, tremor, dyskinesia, subthalamic nucleus, globus pallidus
Brief summary
The goals of this study are to determine if simultaneous bilateral subthalamic nucleus stimulation or simultaneous bilateral globus pallidus stimulation is more effective in reducing symptoms of Parkinson's disease, and if deep brain stimulation or best medical therapy is more effective in improving Parkinson's disease symptoms
Detailed description
Deep Brain Stimulation (DBS) is a promising therapy for Parkinson's disease (PD). Whether DBS is superior to comprehensive best medical therapy or whether some patients or symptoms respond better to DBS in one area of the brain or the other is currently not known. The goals of this project are to compare the effectiveness of DBS and comprehensive medical therapy as treatments for PD, and to compare bilateral DBS at 2 areas of the brain--the subthalamic nucleus (STN) and the globus pallidus (Gpi)--to determine the most effective brain site for surgical intervention In this prospective, randomized, multi-center trial, 316 patients will be enrolled at 13 centers over four and a half years. Patients will initially be randomized to immediate surgery (DBS) or to 6 months of best medical therapy. BMT patients will then proceed into the surgical phase of the trial. The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial. Patients will be followed for two years post surgery (24-30 months). Effective 08/05/05, randomization to the BMT arm has been discontinued since the study has sufficient information to compare the outcomes of DBS and BMT patients at 6 months. The findings will be critically important in establishing the optimal surgical treatment of the disabling symptoms of PD.
Interventions
The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial.
OTHERbest medical therapy
Participants will initially be randomized to DBS or to 6 months of best medical therapy. BMT participants will then proceed into the surgical phase of the trial. Effective 08/05/05, randomization to the BMT arm has been discontinued since the study has sufficient information to compare the outcomes of DBS and BMT patients at 6 months.
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
US Department of Veterans Affairs
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* idiopathic Parkinson's disease, * Hoehn and Yahr stage 2 or worse off medications, * L-dopa responsive but with persistent disabling symptoms (i.e., refractory to best medical treatment with motor fluctuations, dyskinesias), * on stable medical therapy for at least one month prior to enrollment, * age \> 21, * available and willing to be followed-up according to study protocol, and * no intracranial abnormalities that would contraindicate surgery (based on pre-operative magnetic resonance imaging of the brain).
Exclusion criteria
* Parkinson's plus syndromes, * medical contraindications to surgery or stimulation, * active alcohol or drug abuse, * score on minimental status exam 24 or lower, or other neuropsychological dysfunction (e.g., dementia) that would contraindicate surgery, * concurrent participation in another research protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Difference of Time Spent in the 'on' State Without Troublesome Dyskinesia Based on Patient Motor Diaries as Compared to the Baseline. | at six months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change of Scores on the UPDRS for Blinded Assessed Motor Function 'Off' Medication and 'on' Stimulation | at six months | Unified Parkinson's Disease Rating Scale (UPDRS Part III) measured while the patient is off medications and on stimulation at follow-up visits post surgery. UPDRS Part III has 14 items assessing motor skills including facial expression and speech, tremors, rigidity, posture, gait, and bradykinesia. Left and right sides (arms, legs, and hands) are assessed separately for seven of the functions. A summary score ranging from 0 to 108 is generated by adding the 14 specific motor function responses. The motor function (UPDRS part III) assessments are done by turning on the stimulation with and without taking PD medications (on/off) at each in-person visit. The higher score indicates that the condition is worse. |
Countries
United States
Participant flow
Recruitment details
Patient recruitment begun in May 2002 and the discontinuation of randomization to the BMT arm was approved in August 2005 and participating sites received their IRB approval of this change through October 2005. A total of 255 patients were randomized to either BMT or DBS from 7 VA medical centers and 6 affiliated university sites.
Pre-assignment details
An additional 23 patients were screened after signing the informed consent form but not randomized. 11 of them weren't willing to participate in the follow-up visits after intervention, 7 of them had neuropsychological dysfunction, 2 of them were not responsive to levodopa, and 3 had medical contraindication to surgery and/or DBS stimulation.
Participants by arm
| Arm | Count |
|---|---|
| 1: Bilateral Deep Brain Stimulation Bilateral Deep Brain Stimulation
Bilateral Deep Brain Stimulation : The DBS site (STN or GPi) will be assigned on a random basis at the time the patient enters the surgical phase of the trial. | 121 |
| 2: Best Medical Therapy Best Medical Therapy
best medical therapy : Participants will initially be randomized to DBS or to 6 months of best medical therapy. BMT participants will then proceed into the surgical phase of the trial. Effective 08/05/05, randomization to the BMT arm has been discontinued since the study has sufficient information to compare the outcomes of DBS and BMT patients at 6 months. | 134 |
| Total | 255 |
Baseline characteristics
| Characteristic | 2: Best Medical Therapy | 1: Bilateral Deep Brain Stimulation | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 37 Participants | 31 Participants | 68 Participants |
| Age, Categorical Between 18 and 65 years | 97 Participants | 90 Participants | 187 Participants |
| Age, Continuous | 62.3 years STANDARD_DEVIATION 9 | 62.4 years STANDARD_DEVIATION 8.8 | 62.3 years STANDARD_DEVIATION 8.9 |
| Region of Enrollment United States | 134 participants | 121 participants | 255 participants |
| Sex: Female, Male Female | 24 Participants | 23 Participants | 47 Participants |
| Sex: Female, Male Male | 110 Participants | 98 Participants | 208 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 116 / 121 | 97 / 134 |
| serious Total, serious adverse events | 49 / 121 | 15 / 134 |
Outcome results
Primary
The Difference of Time Spent in the 'on' State Without Troublesome Dyskinesia Based on Patient Motor Diaries as Compared to the Baseline.
Time frame: at six months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 1: Bilateral Deep Brain Stimulation | The Difference of Time Spent in the 'on' State Without Troublesome Dyskinesia Based on Patient Motor Diaries as Compared to the Baseline. | 4.6 Hours per day |
| 2: Best Medical Therapy | The Difference of Time Spent in the 'on' State Without Troublesome Dyskinesia Based on Patient Motor Diaries as Compared to the Baseline. | 0 Hours per day |
Secondary
The Change of Scores on the UPDRS for Blinded Assessed Motor Function 'Off' Medication and 'on' Stimulation
Unified Parkinson's Disease Rating Scale (UPDRS Part III) measured while the patient is off medications and on stimulation at follow-up visits post surgery. UPDRS Part III has 14 items assessing motor skills including facial expression and speech, tremors, rigidity, posture, gait, and bradykinesia. Left and right sides (arms, legs, and hands) are assessed separately for seven of the functions. A summary score ranging from 0 to 108 is generated by adding the 14 specific motor function responses. The motor function (UPDRS part III) assessments are done by turning on the stimulation with and without taking PD medications (on/off) at each in-person visit. The higher score indicates that the condition is worse.
Time frame: at six months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 1: Bilateral Deep Brain Stimulation | The Change of Scores on the UPDRS for Blinded Assessed Motor Function 'Off' Medication and 'on' Stimulation | -12.3 units |
| 2: Best Medical Therapy | The Change of Scores on the UPDRS for Blinded Assessed Motor Function 'Off' Medication and 'on' Stimulation | -1.7 units |