Effects of Deep Brain Stimulation on Motor, Mood, and Cognitive Symptoms in Parkinson's Disease

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT00360009
First received: August 2, 2006
Last updated: October 25, 2012
Last verified: October 2012
  Purpose

The purpose of this trial is to study the mood and cognitive effects of deep brain stimulation in Parkinson's disease.


Condition Intervention
Parkinson Disease
Procedure: DBS of the STN
Procedure: DBS of the GPI

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cognition and Mood in Parkinson's Disease (PD) in Subthalamic Nucleus (STN) Versus Globus Pallidus Interna (GPi) Deep Brain Stimulation (DBS)

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Change in Mean T-score of Visual Analogue Mood Scales (VAMS) Angry State [ Time Frame: Pre-surgery baseline to 6 months of DBS stimulation ] [ Designated as safety issue: No ]
    VAMS measure mood states using scales that have a neutral face/word at the top of a vertical line and a specific mood face/word at the bottom of the line. Respondents indicate a point on the line that describes how they are feeling and a raw score between 0-100 is obtained. The raw score is converted to a T-score. The mean pre and post-DBS T-scores are compared. A negative difference in T-score(-0.5) indicates a reduction in mood from pre to post-DBS while a positive T-score difference(2.4) denotes an increase in mood. The larger the absolute T-score value, the greater the mean change in mood.

  • Change in Visual Analogue Mood Scales (VAMS) Afraid State [ Time Frame: Pre-surgery baseline to 6 months of DBS stimulation ] [ Designated as safety issue: No ]
    VAMS measure mood states using scales that have a neutral face/word at the top of a vertical line and a specific mood face/word at the bottom of the line. Respondents indicate a point on the line that describes how they are feeling and a raw score between 0-100 is obtained. The raw score is converted to a T-score. The mean pre and post-DBS T-scores are compared. A negative difference in T-score(-0.5) indicates a reduction in mood from pre to post-DBS while a positive T-score difference(2.4) denotes an increase in mood. The larger the absolute T-score value, the greater the mean change in mood.

  • Change in Visual Analogue Mood Scales (VAMS) Confused State [ Time Frame: Pre-surgery baseline to 6 months of DBS stimulation ] [ Designated as safety issue: No ]
    VAMS measure mood states using scales that have a neutral face/word at the top of a vertical line and a specific mood face/word at the bottom of the line. Respondents indicate a point on the line that describes how they are feeling and a raw score between 0-100 is obtained. The raw score is converted to a T-score. The mean pre and post-DBS T-scores are compared. A negative difference in T-score(-0.5) indicates a reduction in mood from pre to post-DBS while a positive T-score difference(2.4) denotes an increase in mood. The larger the absolute T-score value, the greater the mean change in mood.

  • Change in Visual Analogue Mood Scales (VAMS) Energetic State [ Time Frame: Pre-surgery baseline to 6 months of DBS stimulation ] [ Designated as safety issue: No ]
    VAMS measure mood states using scales that have a neutral face/word at the top of a vertical line and a specific mood face/word at the bottom of the line. Respondents indicate a point on the line that describes how they are feeling and a raw score between 0-100 is obtained. The raw score is converted to a T-score. The mean pre and post-DBS T-scores are compared. A negative difference in T-score(-0.5) indicates a reduction in mood from pre to post-DBS while a positive T-score difference(2.4) denotes an increase in mood. The larger the absolute T-score value, the greater the mean change in mood.

  • Change in Visual Analogue Mood Scales (VAMS) Happy State [ Time Frame: Pre-surgery baseline to 6 months of DBS stimulation ] [ Designated as safety issue: No ]
    VAMS measure mood states using scales that have a neutral face/word at the top of a vertical line and a specific mood face/word at the bottom of the line. Respondents indicate a point on the line that describes how they are feeling and a raw score between 0-100 is obtained. The raw score is converted to a T-score. The mean pre and post-DBS T-scores are compared. A negative difference in T-score(-0.5) indicates a reduction in mood from pre to post-DBS while a positive T-score difference(2.4) denotes an increase in mood. The larger the absolute T-score value, the greater the mean change in mood.

  • Change in Visual Analogue Mood Scales (VAMS) Sad State [ Time Frame: Pre-surgery baseline to 6 months of DBS stimulation ] [ Designated as safety issue: No ]
    VAMS measure mood states using scales that have a neutral face/word at the top of a vertical line and a specific mood face/word at the bottom of the line. Respondents indicate a point on the line that describes how they are feeling and a raw score between 0-100 is obtained. The raw score is converted to a T-score. The mean pre and post-DBS T-scores are compared. A negative difference in T-score(-0.5) indicates a reduction in mood from pre to post-DBS while a positive T-score difference(2.4) denotes an increase in mood. The larger the absolute T-score value, the greater the mean change in mood.

  • Change in Visual Analogue Mood Scales (VAMS) Tense State [ Time Frame: Pre-surgery baseline to 6 months of DBS stimulation ] [ Designated as safety issue: No ]
    VAMS measure mood states using scales that have a neutral face/word at the top of a vertical line and a specific mood face/word at the bottom of the line. Respondents indicate a point on the line that describes how they are feeling and a raw score between 0-100 is obtained. The raw score is converted to a T-score. The mean pre and post-DBS T-scores are compared. A negative difference in T-score(-0.5) indicates a reduction in mood from pre to post-DBS while a positive T-score difference(2.4) denotes an increase in mood. The larger the absolute T-score value, the greater the mean change in mood.

  • Change in Visual Analogue Mood Scales (VAMS) Tired State [ Time Frame: Pre-surgery baseline to 6 months of DBS stimulation ] [ Designated as safety issue: No ]
    VAMS measure mood states using scales that have a neutral face/word at the top of a vertical line and a specific mood face/word at the bottom of the line. Respondents indicate a point on the line that describes how they are feeling and a raw score between 0-100 is obtained. The raw score is converted to a T-score. The mean pre and post-DBS T-scores are compared. A negative difference in T-score(-0.5) indicates a reduction in mood from pre to post-DBS while a positive T-score difference(2.4) denotes an increase in mood. The larger the absolute T-score value, the greater the mean change in mood.


Secondary Outcome Measures:
  • Change in Spielberger State-Trait Anxiety Inventory (STAI) [ Time Frame: Pre-surgery baseline to 6 months of DBS stimulation ] [ Designated as safety issue: Yes ]
    STAI measures anxiety. The questionnaire asks the patients how they feel and allows them to respond on a frequency scale that ranges from 1(not at all) to 4(almost always/very much so). Scores range from 20-80 and the higher the score the greater the anxiety level. The raw score is converted to a T-score. The mean pre and post-DBS T-scores are compared. A negative difference in T-score(-1.4) indicates a reduction in anxiety from pre to post-DBS while a positive T-score difference (0.4) denotes an increase in anxiety. The larger the absolute T-score value,the greater the mean change in anxiety.

  • Change in Beck Depression Inventory (BDI) [ Time Frame: Pre-surgery baseline to 6 months of DBS stimulation ] [ Designated as safety issue: No ]
    BDI is a questionnaire used to measure depression. There is a four-point scale for each of the 21-items of the questionnaire with scores ranging from 0 to 3. Total raw scores range from 0 to 63. The higher the score the greater the severity of depression. The raw score is converted to a T-score. The mean pre and post-DBS T-scores are compared. A negative difference in T-score(-3.7) indicates a reduction in depression from pre to post-DBS while a positive T-score difference (0.4) denotes an increase in depression. The larger the absolute T-score value,the greater the mean change in depression.

  • Change in Letter Fluency Tasks (LFT) [ Time Frame: Pre-surgery baseline to 6 months of DBS stimulation ] [ Designated as safety issue: No ]
    LFT assess frontal lobe function. Performance measure is number of words beginning with a specific letter generated in 1 min. Although no range of possible scores,the more words named in allotted time,the higher the predicted frontal lobe function. Raw score is converted to T-score. The mean pre and post-DBS T-scores are compared. A negative difference in T-score(-2.6) signifies a reduction in task performance from pre to post-DBS while a positive T-score difference(0.7) denotes an increase in task performance. The larger the absolute T-score value,the greater the mean change in performance.


Enrollment: 62
Study Start Date: January 2004
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: STN DBS
Patients who underwent deep brain stimulation (DBS) of the subthalamic nucleus (STN) to treat Parkinson's disease (PD)
Procedure: DBS of the STN
Patients undergo Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) to treat Parkinson's Disease, using a Medtronic 3387 device.
Active Comparator: GPI DBS
Patients who underwent deep brain stimulation (DBS) of the globus pallidus interna (GPi) to treat Parkinson's disease (PD)
Procedure: DBS of the GPI
Patients undergo Deep Brain Stimulation (DBS) of the globus pallidus interna (Gpi) to treat Parkinson's disease, using a Medtronic 3387 device.
No Intervention: no DBS
non-DBS PD patient control group

Detailed Description:

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the globus pallidus interna (GPi) has been shown to relieve the motor symptoms of Parkinson's disease (PD) such as tremor, rigidity, and bradykinesia. However, there is increasing evidence that DBS may be associated with a significant number of mood and cognitive changes.

The aims of this study are to characterize and compare the mood and cognitive effects associated with DBS of the STN and GPi, to delineate regions within or around the STN and GPi that are associated with specific mood and cognitive changes when DBS is applied to these areas, and to assess the relative effectiveness of right versus left STN or GPi stimulation on mood and cognition.

In the study, researchers will compare motor, mood, and cognitive function in people with PD who have had DBS treatment with control subjects (or individuals with PD who have not had DBS). The scientists will characterize the types and incidence of mood and cognitive changes that occur during DBS in each target (STN and GPi), compare the targets, and examine the role of lead location.

The study will enroll 62 participants—10 control subjects (individuals with PD who have not had DBS), and 52 individuals with PD who are scheduled for DBS; the site of the implant (STN or GPi) will be randomly assigned. Participants will perform motor, mood, and cognitive tests (following 6 months of stimulation) over a 2-day period. Duration of the trial for participants is 6 months and includes a 2-night hospital stay.

Findings from this study may help researchers better understand how DBS affects non-motor circuitry.

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Intractable, disabling PD with motor fluctuations, dyskinesias, or freezing episodes
  • Age between 30-75 years
  • Unsatisfactory clinical response to maximal medical management (with trials of both higher and lower doses of anti-Parkinsonian drugs)
  • A stable and optimal medical regimen of anti-Parkinsonian drug therapy for at least three months prior to surgery
  • Patients must be right-handed to be included in the study since mood and cognition are being analyzed and right hemisphere dominant patients could confound the results.

Exclusion Criteria:

  • Clinically significant medical disease that would increase risk of developing pre- or postoperative complications (e.g., significant cardiac or pulmonary disease, uncontrolled hypertension)
  • Evidence of secondary or atypical parkinsonism as suggested by the presence of any of the following: 1) history of stroke(s), 2) exposure to toxins or neuroleptics, 3) history of encephalitis, 4) neurological signs of upper motor neuron disease, cerebellar involvement, supranuclear gaze palsy, or significant orthostatic hypotension
  • MRI scan with significant evidence of brain atrophy or other abnormalities (e.g., lacunar infarcts or iron deposits in the putamen)
  • The Mattis Dementia Rating Scale will be used to assess the level of intellectual function and patients will be excluded with scores reflecting clinical dementia
  • A major psychiatric disorder on the Structured Clinical Interview for DSM-IV (SCID-IV).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00360009

Locations
United States, Florida
University of Florida College of Medicine, Department of Neurology, McKnight Brain Institute, 100 South Newell Drive, L-3 100
Gainesville, Florida, United States, 32610-0236
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Michael Okun, MD University of Florida
Principal Investigator: Kelly Foote, MD University of Florida
Principal Investigator: Hubert Fernandez, MD University of Florida
Principal Investigator: Ramon Rodriguez, MD University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00360009     History of Changes
Other Study ID Numbers: 303-2002, K23NS044997
Study First Received: August 2, 2006
Results First Received: August 5, 2009
Last Updated: October 25, 2012
Health Authority: United States: Federal Government

Keywords provided by University of Florida:
Parkinson's disease
Parkinson disease
PD
deep brain stimulation
DBS
subthalamic nucleus
STN
globus pallidus interna
GPi
mood
motor symptoms
cognition
emotion
memory
attention
tremor
rigidity
bradykinesia

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on October 16, 2014