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

Conditions

Parkinson Disease

Keywords

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

Brief summary

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

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.

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Interventions

PROCEDUREDBS of the STN

Patients undergo Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) to treat Parkinson's Disease, using a Medtronic 3387 device.

PROCEDUREDBS 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

30 Years to 75 Years

Healthy volunteers

No

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).

Design outcomes

Primary

Measure	Time frame	Description
Change in Visual Analogue Mood Scales (VAMS) Tired State	Pre-surgery baseline to 6 months of DBS stimulation	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	Pre-surgery baseline to 6 months of DBS stimulation	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	Pre-surgery baseline to 6 months of DBS stimulation	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	Pre-surgery baseline to 6 months of DBS stimulation	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 Mean T-score of Visual Analogue Mood Scales (VAMS) Angry State	Pre-surgery baseline to 6 months of DBS stimulation	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	Pre-surgery baseline to 6 months of DBS stimulation	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	Pre-surgery baseline to 6 months of DBS stimulation	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	Pre-surgery baseline to 6 months of DBS stimulation	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

Measure	Time frame	Description
Change in Beck Depression Inventory (BDI)	Pre-surgery baseline to 6 months of DBS stimulation	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)	Pre-surgery baseline to 6 months of DBS stimulation	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.
Change in Spielberger State-Trait Anxiety Inventory (STAI)	Pre-surgery baseline to 6 months of DBS stimulation	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
No Deep Brain Stimuation (DBS) Control Group A control group of PD patients that have not undergone surgical intervention (ie. DBS).	10
Subthalamic Nucleus (STN) Deep Brain Stimulation (DBS) Subthalamic Nucleus (STN) Deep Brain Stimulation (DBS) intervention to treat Parkinson's disease (PD)	26
Globus Pallidus Interna (GPi) Deep Brain Stimulation (DBS) Globus Pallidus Interna (GPi) Deep Brain Stimulation (DBS) intervention to treat Parkinson's Disease (PD)	26
Total	62

Baseline characteristics

Characteristic	No Deep Brain Stimuation (DBS) Control Group	Subthalamic Nucleus (STN) Deep Brain Stimulation (DBS)	Globus Pallidus Interna (GPi) Deep Brain Stimulation (DBS)	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	5 Participants	10 Participants	7 Participants	22 Participants
Age, Categorical Between 18 and 65 years	5 Participants	16 Participants	19 Participants	40 Participants
Region of Enrollment United States	10 participants	26 participants	26 participants	62 participants
Sex: Female, Male Female	4 Participants	8 Participants	8 Participants	20 Participants
Sex: Female, Male Male	6 Participants	18 Participants	18 Participants	42 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	0 / 10	25 / 26	23 / 26
serious Total, serious adverse events	0 / 10	6 / 26	8 / 26

Outcome results

Primary

Change in Mean T-score of Visual Analogue Mood Scales (VAMS) Angry State

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.