Deep Brain Stimulation-Induced Mania in Parkinson's Disease (BPD_DBS)

February 21, 2024 updated by: Albino Maia

Understanding Deep Brain Stimulation-induced Mania: Finding Potential Predictors to Optimize Treatment

Parkinson's Disease (PD) is a common and debilitating neurodegenerative disease. While medication can alleviate its symptoms, not all patients will adequately respond to medical therapy. For these cases, deep brain stimulation (DBS) has been used to improve symptoms and quality of life. Nevertheless, this approach is, in some cases, associated with incapacitating neuropsychiatric side-effects, including mood disturbances, such as DBS-induced mania. While this condition has important functional short- and long-term consequences for quality of life and prognosis, its pathophysiology is still poorly understood. In this project the investigators propose to conduct a retrospective and naturalistic study in PD patients in whom DBS stimulation resulted in mania or mixed state episode, to clarify if specific sociodemographic and clinical predictors, namely stimulation parameters and target locations, might be associated to the occurrence of this neuropsychiatric adverse event. Additionally, the investigators aim to clarify if the occurrence of DBS-induced mania results from the impact of specific stimulation parameters and/or target locations in functional connectivity networks. To explore this question, the investigators will use different neuroimaging analysis methods termed lesion topography analysis and lesion network mapping, in order to compute maps of the stimulated regions topography and the functional networks that are associated with DBS-mania, respectively. The data that will be analyzed in this project, including neuroimages, will be obtained retrospectively, by different Movement Disorders and Functional Surgery Groups in the context of Deep Brain Stimulation, and that has been collected according to their usual clinical practice.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Parkinson's Disease is the second most common neurodegenerative disorder, characterized by very debilitating motor and non-motor symptoms. While medication can alleviate the impact of this disease in patient's daily life, not all patients will respond adequately to treatment, its benefits may not be long-lasting and/or incapacitating side-effects may result. For these cases, DBS has been used to improve symptoms and quality of life. Nevertheless, this approach may have clinically significant side-effects. In fact, important neuropsychiatric adverse events can occur as a result of DBS stimulation, including DBS-induced mania. This is a debilitating mood disorder, frequently associated to a decrease in DBS efficacy due to the need to change/alter stimulation parameters or switch off the device entirely with the patient losing the benefits and the improving quality of life associated with the amelioration of his motor (but also non-motor) symptoms provided by DBS-stimulation. However, reliable predictors for its occurrence are lacking and its pathophysiology is still poorly understood. In this project, the investigators aim to clarify if there are specific DBS electrode locations and/or stimulation parameters associated to development of DBS-induced Mania while additionally determining other potential sociodemographic and clinical predictors. The investigators also aim to further explore if DBS-induced mania results from the impact of specific stimulation parameters and/or target locations in functional connectivity networks.

The investigators hypothesize that specific stimulation parameters and treatment targets associated with DBS-induced mania stimulation will impact particular subcortical brain regions, alongside other clinical and sociodemographic predictors. Additionally, the investigators hypothesize that such specific pattern of stimulation will be associated to specific dysfunctional brain connectivity networks. To address these hypotheses, the investigators propose three specific aims:

  1. To determine if there are specific DBS electrode location and/or stimulation parameters associated to development of DBS-induced Mania;
  2. To determine if there are specific sociodemographic and/or clinical predictors for the emergence of DBS-induced Mania;
  3. To explore if specific functional connectivity networks are associated to the DBS target location and/or stimulation parameters associated with Mania.

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Portugal
      • Lisbon, Portugal, 1400-038
        • Recruiting
        • Champalimaud Foundation
        • Contact:
        • Sub-Investigator:
          • Gonçalo Cotovio, MD
        • Principal Investigator:
          • Albino J. Oliveira-Maia, MD, MPH, PhD
        • Sub-Investigator:
          • Francisco Viana
        • Sub-Investigator:
          • Sara Penedos, MD
        • Sub-Investigator:
          • J. Bernardo Barahona-Correa, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study cohort will be collected retrospectively from DBS surgery databases from different Movement Disorders and Functional Surgery Groups and further analyzed at the Champalimaud Neuropsychiatry Unit. Data collection will be conducted by each center independently under the approval of their respective Ethics Committees. The data that will be analyzed in this project, including neuroimages, has been collected according to the usual clinical practice of the Movement Disorders and Functional Surgery Groups.

Description

DBS-induced mania cohort:

Inclusion Criteria:

  • Age≥18-years-old;
  • Patients diagnosed with PD who were submitted to DBS surgery irrespective of its target;
  • Manic episode or mixed affective state diagnosed after surgery and associated to DBS modulation, i.e., after switching on the device or changing modulation parameters.

Exclusion Criteria:

  • Patients diagnosed with bipolar disorder, or manic episode, or mixed affective state before the age of 18
  • Patients diagnosed with bipolar disorder, or manic episode, or mixed affective state, before DBS surgery.

DBS Control Cohort:

A control cohort will also be collected. These patients will also meet the aforementioned inclusion and exclusion criteria with the exception of not having presented a manic episode or mixed affective state diagnosed after surgery and associated to DBS modulation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
DBS-induced Mania Cohort
Patients diagnosed with Parkinson's Disease (PD) who were submitted to deep brain stimulation (DBS) surgery irrespective of its target and who developed a manic episode or mixed affective state diagnosed after surgery and associated to DBS modulation, i.e., after switching on the device or changing modulation parameters.
Other: No Intervention / Exposure
No intervention / exposure since this is an observational study
DBS Control Cohort
Patients diagnosed with PD who were submitted to DBS surgery irrespective of its target and who did not develop DBS-induced mania.
Other: No Intervention / Exposure
No intervention / exposure since this is an observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Topographic localization of volume of tissue activation (VTA) in DBS-induced mania
Time Frame: From DBS parametres change until the date of first documented manic symptoms, assessed up to 24 months
Differences in voxel-wise topographic localization of VTAs between DBS-induced mania in Parkinson's Disease (PD) and DBS PD controls. VTAs will be obtained using DBS electrodes locations and stimulation parameters.
From DBS parametres change until the date of first documented manic symptoms, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sociodemographic and/or clinical predictors of DBS-induced mania
Time Frame: From DBS parametres change until the date of first documented manic symptoms, assessed up to 24 months
Level of prediction of different models for DBS-induced mania in PD, when compared to DBS PD controls. Such models will explore different sociodemographic and/or clinical variables.
From DBS parametres change until the date of first documented manic symptoms, assessed up to 24 months
Connectivity profile of volume of tissue activation (VTA) in DBS-induced mania
Time Frame: From DBS parametres change until the date of first documented manic symptoms, assessed up to 24 months
Differences in voxel-wise connectivity profile of VTAs between DBS-induced mania in PD and DBS PD controls.
From DBS parametres change until the date of first documented manic symptoms, assessed up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Albino Maia

Collaborators

Centro Hospitalar Lisboa Ocidental
Centro Hospitalar De São João, E.P.E.
Centro Hospitalar e Universitário de Coimbra, E.P.E.
Centro Hospitalar de Lisboa Central

Investigators

  • Principal Investigator: Albino J. Oliveira-Maia, MD, MPH, PhD, Champalimaud Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 25, 2021

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

June 28, 2022

First Submitted That Met QC Criteria

July 1, 2022

First Posted (Actual)

July 6, 2022

Study Record Updates

Last Update Posted (Actual)

February 23, 2024

Last Update Submitted That Met QC Criteria

February 21, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BPD_DBS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to make individual participant data available to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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