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Phase II Subthalamic Nucleus (STN) vs. Globus Pallidus (GPi) Trial

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ClinicalTrials.gov Identifier: NCT01076452
Recruitment Status : Completed
First Posted : February 26, 2010
Results First Posted : January 15, 2014
Last Update Posted : July 14, 2014
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Medtronic
Information provided by (Responsible Party):
VA Office of Research and Development ( US Department of Veterans Affairs )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Condition Parkinson's Disease
Intervention Device: Bilateral Deep Brain Stimulation
Enrollment 299
Recruitment Details 299 subjects were enrolled into the study from May 2002 to September 2006 at 13 clinical sites including 7 VA Medical Centers and 6 affiliated university medical centers.
Pre-assignment Details  
Arm/Group Title Arm 1 Arm 2
Hide Arm/Group Description

STN (Subthalamic Nucleus)

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.

GPi (Globus Pallidus)

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.

Period Title: Overall Study
Started 147 152
Completed 123 138
Not Completed 24 14
Arm/Group Title Arm 1 Arm 2 Total
Hide Arm/Group Description

STN (Subthalamic Nucleus)

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.

GPi (Globus Pallidus)

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.

Total of all reporting groups
Overall Number of Baseline Participants 147 152 299
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 147 participants 152 participants 299 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
113
  76.9%
117
  77.0%
230
  76.9%
>=65 years
34
  23.1%
35
  23.0%
69
  23.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 147 participants 152 participants 299 participants
61.9  (8.7) 61.8  (8.7) 61.8  (8.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 147 participants 152 participants 299 participants
Female
31
  21.1%
19
  12.5%
50
  16.7%
Male
116
  78.9%
133
  87.5%
249
  83.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 147 participants 152 participants 299 participants
147 152 299
1.Primary Outcome
Title The Change From Baseline in the UPDRS-III Score at 24 Months With Deep-brain Stimulation and Without Medication.
Hide Description The primary outcome measure for the comparison of GPi deep brain stimulation (DBS) to STN DBS is the motor function score of the 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. 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. A summary score ranging from 0 to 108 is generated by adding the 14 specific motor function responses. The higher score indicates the worse motor function.
Time Frame Baseline and 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title STN (Subthalamic Nucleus) GPi (Globus Pallidus)
Hide Arm/Group Description:

STN (Subthalamic Nucleus)

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.

GPi (Globus Pallidus)

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.

Overall Number of Participants Analyzed 147 152
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-12.9
(-15.4 to -10.4)
-13.1
(-15.5 to -10.8)
2.Secondary Outcome
Title The Change From Baseline in the UPDRS Scores Part I (Mentation) at 24 Months.
Hide Description The UPDRS has four parts (Parts I-IV) in which a total of 42 disease characteristics are assessed. Most characteristics are assessed according to their severity on a 0-4 scale (0 = normal, 4 = most substantial impairment), and some are assessed only for absence (score = 0) or presence (score = 1). Part I has four items assessing intellectual impairment, thought disorder, depression and motivation. A summary score ranging from 0 to16 is generated by adding the four items. The higher score indicates worse condition.
Time Frame Baseline and 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title STN (Subthalamic Nucleus) GPi (Globus Pallidus)
Hide Arm/Group Description:

STN (Subthalamic Nucleus)

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.

GPi (Globus Pallidus)

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.

Overall Number of Participants Analyzed 147 152
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.6  (2.2) 0.4  (2.2)
3.Secondary Outcome
Title The Change From Baseline in the UPDRS Scores Part II (Activity of Daily Living) at 24 Months.
Hide Description The UPDRS has four parts (Parts I-IV) in which a total of 42 disease characteristics are assessed. Most characteristics are assessed according to their severity on a 0-4 scale (0 = normal, 4 = most substantial impairment), and some are assessed only for absence (score = 0) or presence (score = 1). Part II has 13 items focusing on activities of daily living including walking, writing, dressing and speech. A summary score ranging from 0 to 52 is generated by adding the 13 items. The higher score indicates worse condition.
Time Frame Baseline and 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title STN (Subthalamic Nucleus) GPi (Globus Pallidus)
Hide Arm/Group Description:

STN (Subthalamic Nucleus)

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.

GPi (Globus Pallidus)

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.

Overall Number of Participants Analyzed 147 152
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.3  (6.6) -3.4  (6.5)
4.Secondary Outcome
Title The Change From Baseline in the UPDRS Scores Part IV (Complication of Therapy) at 24 Months.
Hide Description The UPDRS has four parts (Parts I-IV) in which a total of 42 disease characteristics are assessed. Most characteristics are assessed according to their severity on a 0-4 scale (0 = normal, 4 = most substantial impairment), and some are assessed only for absence (score = 0) or presence (score = 1). Part IV includes four categories (11 items) related to dyskinesias, clinical fluctuations of symptoms, and other complications. A summary score ranging from 0 to 23 is generated by adding the four items. The higher score indicates worse condition.
Time Frame Baseline and 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title STN (Subthalamic Nucleus) GPi (Globus Pallidus)
Hide Arm/Group Description:

STN (Subthalamic Nucleus)

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.

GPi (Globus Pallidus)

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.

Overall Number of Participants Analyzed 147 152
Mean (Standard Deviation)
Unit of Measure: units on a scale
-3.9  (3.4) -3.4  (3.8)
Time Frame 24 months
Adverse Event Reporting Description Adverse events were identified rigorously and categorized as mild, moderate, or severe. Serious adverse events included any event that resulted in death, disability, prolonged or new hospitalization; was life-threatening; or required medical or surgical intervention to prevent one of the above outcomes.
 
Arm/Group Title Arm 1 Arm 2
Hide Arm/Group Description

STN (Subthalamic Nucleus)

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.

GPi (Globus Pallidus)

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.

All-Cause Mortality
Arm 1 Arm 2
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm 1 Arm 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   83/147 (56.46%)      77/152 (50.66%)    
Blood and lymphatic system disorders     
Anaemia * 1  1/147 (0.68%)  2 1/152 (0.66%)  1
Cardiac disorders     
Coronary Artery Disease * 1  3/147 (2.04%)  3 1/152 (0.66%)  1
Cardiac Failure Congestive * 1  2/147 (1.36%)  3 0/152 (0.00%)  0
Myocardial infarction * 1  1/147 (0.68%)  1 1/152 (0.66%)  2
Angina Pectoris * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Angina Unstable * 1  1/147 (0.68%)  1 0/152 (0.00%)  0
Atrial Fibrillation * 1  1/147 (0.68%)  1 1/152 (0.66%)  1
Atrioventricular Block Complete * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Coronary Artery Occlusion * 1  1/147 (0.68%)  1 0/152 (0.00%)  0
Coronary Artery Restenosis * 1  1/147 (0.68%)  1 0/152 (0.00%)  0
Palpitations * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Sick Sinus Syndrome * 1  1/147 (0.68%)  1 0/152 (0.00%)  0
Gastrointestinal disorders     
Gastroesophageal reflux disease * 1  2/147 (1.36%)  2 2/152 (1.32%)  2
Inguinal hernia * 1  2/147 (1.36%)  2 2/152 (1.32%)  2
gastrointestinal disorders * 1  1/147 (0.68%)  1 0/152 (0.00%)  0
Appendicitis Perforated * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Constipation * 1  1/147 (0.68%)  1 0/152 (0.00%)  0
Gastric Polyps * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Gastroduodenitis * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Hiatus Hernia * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Intestinal Obstruction * 1  1/147 (0.68%)  1 0/152 (0.00%)  0
Intestinal Perforation * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Oesophageal Spasm * 1  1/147 (0.68%)  1 0/152 (0.00%)  0
Oesophagitis * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Rectal Hemorrhage * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Small Instestinal Obstruction * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
General disorders     
Adverse Drug Reaction * 1  2/147 (1.36%)  2 2/152 (1.32%)  2
Chest Pain * 1  2/147 (1.36%)  2 1/152 (0.66%)  1
Chest Discomfort * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Fatigue * 1  1/147 (0.68%)  1 0/152 (0.00%)  0
Gait Disturbance * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Implant Site Reaction * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Mechanical Complication of Implant * 1  1/147 (0.68%)  1 0/152 (0.00%)  0
Oedema Peripheral * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Pyrexia * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Immune system disorders     
drug hypersensitivity * 1  2/147 (1.36%)  2 1/152 (0.66%)  1
Infections and infestations     
Implantation-site infection * 1  11/147 (7.48%)  14 12/152 (7.89%)  17
Pneumonia * 1  4/147 (2.72%)  4 8/152 (5.26%)  8
Cellulitis * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Clostridium Difficile Sepsis * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Clostridium Difficile Colitis * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Diverticulitis * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Localized Infection * 1  1/147 (0.68%)  1 0/152 (0.00%)  0
Orchitis * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Pyelonephritis * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Sepsis * 1  2/147 (1.36%)  2 0/152 (0.00%)  0
Sialoadenitis * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Tooth Abscess * 1  0/147 (0.00%)  0 1/152 (0.66%)  1
Urinary Tract Infection * 1  1/147 (0.68%)  1 1/152 (0.66%)  1
Urosepsis * 1  1/147 (0.68%)  1 1/152 (0.66%)  1
Viral Infection * 1  0/147 (0.00%)  0 2/152 (1.32%)  2
Injury, poisoning and procedural complications     
Fall * 1  13/147 (8.84%)  16 5/152 (3.29%)  5
Medical device complication * 1  4/147 (2.72%)  5 2/152 (1.32%)  2
Road Traffic accidents * 1  3/147 (2.04%)  4 0/152 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Lumbar spine stenosis * 1  2/147 (1.36%)  2 3/152 (1.97%)  4
Osteoarthritis * 1  2/147 (1.36%)  2 3/152 (1.97%)  3
Nervous system disorders     
Syncope * 1  4/147 (2.72%)  4 1/152 (0.66%)  1
Dyskinesia * 1  3/147 (2.04%)  3 1/152 (0.66%)  1
Cerebral hemorrhage * 1  2/147 (1.36%)  2 1/152 (0.66%)  1
Stroke * 1  3/147 (2.04%)  3 0/152 (0.00%)  0
Intracranial Hemorrhage * 1  0/147 (0.00%)  0 3/152 (1.97%)  3
Psychiatric disorders     
Confusional state * 1  5/147 (3.40%)  5 2/152 (1.32%)  2
Mental Status Change * 1  1/147 (0.68%)  2 4/152 (2.63%)  4
Depression * 1  1/147 (0.68%)  1 4/152 (2.63%)  4
Suicidal Depression * 1  1/147 (0.68%)  1 2/152 (1.32%)  2
Suicidal Ideation * 1  1/147 (0.68%)  1 0/152 (0.00%)  0
Suicide Attempt * 1  2/147 (1.36%)  2 0/152 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm 1 Arm 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   145/147 (98.64%)      150/152 (98.68%)    
Blood and lymphatic system disorders     
Aneamia * 1  7/147 (4.76%)  7 9/152 (5.92%)  14
Eye disorders     
Diplopia * 1  7/147 (4.76%)  7 3/152 (1.97%)  3
Visual Disturbance * 1  7/147 (4.76%)  7 12/152 (7.89%)  12
Gastrointestinal disorders     
Constipation * 1  48/147 (32.65%)  58 56/152 (36.84%)  65
Dysphagia * 1  66/147 (44.90%)  84 71/152 (46.71%)  85
Gastrooesophageal reflux disease * 1  12/147 (8.16%)  15 10/152 (6.58%)  10
Nausea * 1  28/147 (19.05%)  32 18/152 (11.84%)  19
Vomiting * 1  6/147 (4.08%)  6 8/152 (5.26%)  8
General disorders     
adverse drug reaction * 1  10/147 (6.80%)  12 7/152 (4.61%)  14
Asthenia * 1  11/147 (7.48%)  13 5/152 (3.29%)  5
Chest Pain * 1  11/147 (7.48%)  12 10/152 (6.58%)  10
Fatigue * 1  26/147 (17.69%)  29 24/152 (15.79%)  31
Gait Disturbance * 1  71/147 (48.30%)  94 70/152 (46.05%)  98
Oedema Peripheral * 1  17/147 (11.56%)  18 13/152 (8.55%)  13
Pain * 1  50/147 (34.01%)  75 43/152 (28.29%)  65
Infections and infestations     
Implant sight infection * 1  12/147 (8.16%)  15 13/152 (8.55%)  19
Pneumonia * 1  7/147 (4.76%)  8 12/152 (7.89%)  12
Urinary Tract Infection * 1  22/147 (14.97%)  28 16/152 (10.53%)  29
Injury, poisoning and procedural complications     
Fall * 1  103/147 (70.07%)  198 100/152 (65.79%)  157
Incision Site Pain * 1  31/147 (21.09%)  33 30/152 (19.74%)  31
Procedural Pain * 1  22/147 (14.97%)  32 29/152 (19.08%)  41
Investigations     
Blood Pressure increase * 1  10/147 (6.80%)  12 10/152 (6.58%)  18
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  23/147 (15.65%)  26 9/152 (5.92%)  10
Back Pain * 1  22/147 (14.97%)  22 24/152 (15.79%)  25
Muscle rigidity * 1  50/147 (34.01%)  74 41/152 (26.97%)  61
Muscle spasms * 1  15/147 (10.20%)  16 6/152 (3.95%)  8
Musculoskeletal Pain * 1  11/147 (7.48%)  12 15/152 (9.87%)  15
Musculoskeletal Stiffness * 1  55/147 (37.41%)  78 48/152 (31.58%)  79
Nervous system disorders     
Freezing Phenomenon * 1  65/147 (44.22%)  93 80/152 (52.63%)  113
Akinesia * 1  30/147 (20.41%)  41 33/152 (21.71%)  49
Balance disorder * 1  63/147 (42.86%)  81 66/152 (43.42%)  86
Bradykinesia * 1  47/147 (31.97%)  69 57/152 (37.50%)  86
Drooling * 1  56/147 (38.10%)  68 51/152 (33.55%)  54
Dyskinesia * 1  76/147 (51.70%)  116 62/152 (40.79%)  86
Dystonia * 1  60/147 (40.82%)  85 68/152 (44.74%)  89
Headache * 1  61/147 (41.50%)  72 61/152 (40.13%)  71
memory Impairment * 1  13/147 (8.84%)  14 23/152 (15.13%)  24
Motor Dysfunction * 1  52/147 (35.37%)  70 57/152 (37.50%)  84
Poor Quality Sleep * 1  9/147 (6.12%)  11 11/152 (7.24%)  12
Somnolence * 1  18/147 (12.24%)  19 18/152 (11.84%)  20
Speech Disorder * 1  78/147 (53.06%)  105 70/152 (46.05%)  88
Tremor * 1  58/147 (39.46%)  83 54/152 (35.53%)  79
Psychiatric disorders     
Abnormal Dreams * 1  13/147 (8.84%)  14 13/152 (8.55%)  14
Alcohol Abuse * 1  10/147 (6.80%)  10 14/152 (9.21%)  15
Anxiety * 1  30/147 (20.41%)  34 23/152 (15.13%)  27
Confusional State * 1  69/147 (46.94%)  98 58/152 (38.16%)  79
Depression * 1  80/147 (54.42%)  101 69/152 (45.39%)  94
Hallucination * 1  21/147 (14.29%)  25 21/152 (13.82%)  26
Insomnia * 1  40/147 (27.21%)  47 35/152 (23.03%)  40
Reproductive system and breast disorders     
Sexual Dysfunction * 1  13/147 (8.84%)  14 23/152 (15.13%)  23
Respiratory, thoracic and mediastinal disorders     
Cough * 1  12/147 (8.16%)  12 13/152 (8.55%)  14
Dyspnonea * 1  14/147 (9.52%)  15 18/152 (11.84%)  18
Skin and subcutaneous tissue disorders     
Hyperhidrosis * 1  28/147 (19.05%)  37 31/152 (20.39%)  44
Rash * 1  10/147 (6.80%)  10 12/152 (7.89%)  13
Vascular disorders     
Hypertension * 1  17/147 (11.56%)  18 22/152 (14.47%)  28
Orthostatic Hypotension * 1  44/147 (29.93%)  66 42/152 (27.63%)  58
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.0
We observed differences between STN and GPi DBS groups on several secondary measures but these findings should be interpreted cautiously. We did not adjust for repeated significance tests and the differences may have limited clinical significance.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Frances M. Weaver, Ph.D
Organization: Hines Veterans Affairs Hospital Center for Management of Complex Chronic Care
Phone: 708-202-8387 ext 25866
Publications of Results:
Responsible Party: VA Office of Research and Development ( US Department of Veterans Affairs )
ClinicalTrials.gov Identifier: NCT01076452     History of Changes
Other Study ID Numbers: 468 Phase II
VA-NINDS-01 ( Other Identifier: NIH-NINDS )
First Submitted: February 24, 2010
First Posted: February 26, 2010
Results First Submitted: September 11, 2013
Results First Posted: January 15, 2014
Last Update Posted: July 14, 2014