Antidepressant Effect of Deep Brain Stimulation in Parkinson's Disease Patients

NCT ID: NCT00885222

Last Updated: 2010-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2010-05-31

Brief Summary

The purpose of this study is:

1. To determine, in the context of a prospective clinical trial, whether stimulation parameters in PD patients treated with DBS, are associated with antidepressant effects.

2. To determine whether these antidepressant effects are related to or independent of changes in the motor features of PD.

3. To establish a computerized database that includes stimulation parameters and clinical parameters in PD patients treated with DBS.

4. To develop a computer-assisted decision making protocol for programming of DBS parameters in both depressed and non-depressed PD patients.

Detailed Description

Depressive symptoms of PD patients are major predictors of their prognosis and quality of life. Therefore, successful treatment of depression is crucial in PD patients. Using deep brain stimulation as an antidepressant (or to augment a standard antidepressant) could be a promising new direction. The hypothesis to be tested in the current project is that treatment with deep brain stimulation will improve both the neurological and the psychiatric (depressive) symptoms of PD. It is further hypothesized that the improvement in depressive symptoms will not be a simple consequence of improvement in neurological status. Data from this open label study will form the basis for planning a larger scale controlled trial in depressed PD patients and exploratory studies in patients with major depression who do not have PD.

Today, programming of DBS is based on the neurological evaluation of the motor features of PD. If our hypothesis is proven, i.e. parameter manipulation of DBS affects the mental features of PD, it is crucial to establish a valid database that will enable to study these effects. Moreover, such a detailed database will be the basis for the development of a computer-assisted decision making protocol for programming of DBS. A novel decision making protocol will maximize the benefits of DBS in both depressed and non-depressed PD patients.

Conditions

Parkinson's Disease; Major Depressive Disorder

Study Design

• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

PD patient that were treated with STN DBS and developed depression after the surgery (n=5).

Group Type: ACTIVE_COMPARATOR

DBS parameters setting

Intervention Type: DEVICE

DBS parameters will be set to increase the DBS affected volume to include both the cognitive and limbic territories in addition to the dorso-lateral motor territories of the STN. This novel approach to parameter selection is directed to achieve improvement in cognitive and limbic as well as motor domains of PD. The patients will therefore be assessed for cognitive, limbic and motor state at multiple time points; there will be a baseline assessment prior to starting treatment (prior to DBS surgery and/or prior to parameters changes); thereafter assessments will follow the stimulation parameter changes; thereafter follow-up assessments at 6 - 12 months. Stimulation parameters will be changed every 2 weeks or earlier if an urgent clinical state emerges. Patients with depression will be monitored for antidepressant effects of stimulation changes. Patients without depression will be monitored for evidence of treatment emergent depression.

2

PD patients with depression that are candidates for STN DBS (n=5).

Group Type: ACTIVE_COMPARATOR

DBS parameters setting

Intervention Type: DEVICE

DBS parameters will be set to increase the DBS affected volume to include both the cognitive and limbic territories in addition to the dorso-lateral motor territories of the STN. This novel approach to parameter selection is directed to achieve improvement in cognitive and limbic as well as motor domains of PD. The patients will therefore be assessed for cognitive, limbic and motor state at multiple time points; there will be a baseline assessment prior to starting treatment (prior to DBS surgery and/or prior to parameters changes); thereafter assessments will follow the stimulation parameter changes; thereafter follow-up assessments at 6 - 12 months. Stimulation parameters will be changed every 2 weeks or earlier if an urgent clinical state emerges. Patients with depression will be monitored for antidepressant effects of stimulation changes. Patients without depression will be monitored for evidence of treatment emergent depression.

3

PD patients without depression that are candidates for STN DBS (n=10).

Group Type: ACTIVE_COMPARATOR

DBS parameters setting

Intervention Type: DEVICE

DBS parameters will be set to increase the DBS affected volume to include both the cognitive and limbic territories in addition to the dorso-lateral motor territories of the STN. This novel approach to parameter selection is directed to achieve improvement in cognitive and limbic as well as motor domains of PD. The patients will therefore be assessed for cognitive, limbic and motor state at multiple time points; there will be a baseline assessment prior to starting treatment (prior to DBS surgery and/or prior to parameters changes); thereafter assessments will follow the stimulation parameter changes; thereafter follow-up assessments at 6 - 12 months. Stimulation parameters will be changed every 2 weeks or earlier if an urgent clinical state emerges. Patients with depression will be monitored for antidepressant effects of stimulation changes. Patients without depression will be monitored for evidence of treatment emergent depression.

Interventions

DBS parameters setting

DBS parameters will be set to increase the DBS affected volume to include both the cognitive and limbic territories in addition to the dorso-lateral motor territories of the STN. This novel approach to parameter selection is directed to achieve improvement in cognitive and limbic as well as motor domains of PD. The patients will therefore be assessed for cognitive, limbic and motor state at multiple time points; there will be a baseline assessment prior to starting treatment (prior to DBS surgery and/or prior to parameters changes); thereafter assessments will follow the stimulation parameter changes; thereafter follow-up assessments at 6 - 12 months. Stimulation parameters will be changed every 2 weeks or earlier if an urgent clinical state emerges. Patients with depression will be monitored for antidepressant effects of stimulation changes. Patients without depression will be monitored for evidence of treatment emergent depression.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Clinically definite PD treated / candidates for treatment with DBS (patients with advanced idiopathic PD who are deemed appropriate for DBS surgery).

2. Patients will be included in the study irrespective of whether a diagnosis of major depression (mild to moderate but not severe MDD) is fulfilled at baseline. Patients without depression will be monitored in the study for evidence of treatment emergent depression. Patients with depression will be monitored for antidepressant effects of stimulation change.

3. Age 40-75 years

4. Male or female.

5. Competent and willing to give written informed consent.

Exclusion Criteria

1. Significant suicidal risk [Hamilton Depression scale item 3 (suicide) >2].

2. Comorbidity with any Psychotic Disorder, Bipolar Disorder, Post Traumatic Stress Disorder (PTSD), Eating Disorder.

3. Lifetime history of substance or alcohol dependence or of abuse in the preceding 12 months

4. Significant cognitive decline, as measured by Addenbrooke's Cognitive Examination (ACE) and the Frontal Assessment Battery (FAB).

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hadassah Medical Organization

OTHER

Sponsor Role: lead

Responsible Party

Hadassah Medical Organization, Jerusalem, Israel

Principal Investigators

Renana Eitan, MD

Role: PRINCIPAL_INVESTIGATOR

Hadassah Medical Organization

Zvi Israel, MD

Role: STUDY_CHAIR

Hadassah Medical Organization

Hagai Bergman, MD

Role: STUDY_CHAIR

Hadassah Medical Organization

Bernard Lerer, MD

Role: STUDY_CHAIR

Hadassah Medical Organization

Locations

Hadassah Medical Organization

Jerusalem, , Israel

Countries

Israel

Other Identifiers

Eitan-DBS-PD-MDD-HMO-CTIL

Identifier Type: -

Identifier Source: org_study_id