DBS and SCS Therapy Improve Motor Function in Multiple System Atrophy With Predominant Parkinsonism

January 11, 2021 updated by: zhangyuqing

Deep Brain Stimulation and Spinal Cord Stimulation Therapy Improve Motor Function in Multiple System Atrophy With Predominant Parkinsonism: a Multi-center, Prospective, Open Label Clinical Trial

Multiple system atrophy (MSA) is a debilitating and fatal neurodegenerative disorder and symptomatic therapeutic strategies are still limited.The parkinsonian type of MSA (MSA-P) has parkinsonian symptoms as its prominent manifestation, although Deep brain stimulation (DBS) at the subthalamic nucleus or globus pallidus interna has been an established treatment for Parkinson's disease patients, it is mostly ineffective in MSA-P patients, the improvement in motor function as short-lasting and rapidly followed by the early appearance of freezing of gait (FOG) and postural instability that counteracted DBS benefits and often leads to significant disability and loss of quality of life. Recently, some pilot studies demonstrated the safety and significant therapeutic outcome of SCS for FOG.The purpose of this clinical study is to understand the effectiveness of DBS combined with SCS for symptomatic treatment of MSA-P.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Multiple system atrophy (MSA) is a debilitating and fatal neurodegenerative disorder that characterized pathologically by α-synuclein (aSyn) accumulation in oligodendrocytes, the myelinating glial cells of the central nervous system (CNS), and symptomatic therapeutic strategies are still limited.

The parkinsonian type of multiple system atrophy (MSA-P) has parkinsonian symptoms as its prominent manifestation and may have an initial but short-lived response to levodopa (L-dopa). Deep brain stimulation (DBS) at the subthalamic nucleus (STN) or globus pallidus interna(GPi) has been an established treatment for Parkinson's disease(PD) patients with medically intractable fluctuations and has shown long-term efficacy to improve parkinsonian motor symptoms, such as bradykinesia, rigidity and rest tremor. However, DBS therapy is mostly ineffective in MSA patients. For the patients with MSA-P, improvement in motor function is short-lasting and rapidly followed by the early appearance of freezing of gait (FOG) and postural instability that counteracted DBS benefits and often leads to significant disability and loss of quality of life. Dopaminergic therapy or other symptomatic medications only offer limited alleviation of FOG and often lose their effect over time. Spinal cord stimulation (SCS) is a well-established therapy for treating chronic lower back or low limb pain neuropathic pain. Recently, some pilot studies demonstrated the safety and significant therapeutic outcome of SCS for FOG in PD, MSA-P and primary progressive freezing gait（PPFG）patients.

Can combined DBS with SCS be an alternative approach for symptomatic treatment of parkinsonian symptoms and gait-associated problems in patients with MSA-P? The purpose of this clinical study is to understand the combined treatment effectiveness for MSA-P.

It's a a multi-center, prospective, open label clinical study with a 12 months follow-up period. The intended study population is individuals suffering from multiple system atrophy with predominant parkinsonism. Each subject will complete an enrollment/screening/baseline visit, an DBS&SCS implant and activation visit, and 3 months, and 12months follow-up visits. Data collected at the enrollment visit after the consent process includes: demographics, baseline clinical status, MSA-related medical history, and inclusion/exclusion criteria assessment.Baseline assessment includes: Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III,New Freezing of Gait Questionnaire (NFOGQ), Gait and Fall Questionnaire (GFQ), PD-related quality of life (PDQ-39) and Berg Balance Scale(BBS). The participants will proceed to implantation after satisfying implant inclusion and exclusion criteria. Medtronic Model 3389 DBS electrodes (Medtronic, U.S.A.) will be implanted in the STN bilaterally using a stereotactic technique, connected to a dual-channel ACTIVA Neurostimulator (Medtronic); Paddle-shaped SCS electrode with 16 contacts (AdaptiveStim® 39, 565; Medtronic, USA) will be implanted into the epidural space at the thoracic levels ranging from T10 to T12. Electrode positions of DBS will be verified by postoperative CT-MRI image fusion and electrode position of SCS will be verified by X-ray. The stimulators will be turned on within 1 month after electrode implantation surgery. The stimulation parameters could vary freely, but medications will be kept constant during the study period. At the end of month 12, participants will enter the long-term follow-up in which medications could vary freely.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

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

Study Locations

  • China
      • Beijing, China
        • Recruiting
        • Capital Medical University of Xuanwu Hospital

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

26 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

inclusion criteria:

  1. meet the clinical diagnostic criteria of possible MSA-P;
  2. with moderate to severe parkinsonism motor symptoms;
  3. accept levodopa treatment for at least 6 months, and stable medication dose for at least 4 weeks;

exclusion criteria:

  1. severe orthostatic hypotension;
  2. score of Hamilton Depression Scale is more than 24.
  3. score of Mini-mental State Examination is less than 24;
  4. elevated risks for bleeding
  5. with evident lesions on MRI structural images at T8-12 spinal cord segment

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

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Deep bain stimulation and Spinal cord stimulation therapy
The patients in this group will receive bilateral STN-DBS and SCS stimulation
Procedure: Bilateral STN-DBS and T10-T12 SCS
simultaneous stimulation of bilaterally-STN-DBS combined with spinal cord stimulation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
change in motor examination( Movement Disorders Society's revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III) at 3 months postoperatively
Time Frame: 3 months after surgery
demonstrate the statistically significant difference in change of motor score (MDS-UPDRS III) from baseline( Off medication) to 3months(On stimulation/Off medication); MDS-UPDRS III ranges from 0 to 132, higher scores mean a worse outcome .
3 months after surgery
change in motor examination( Movement Disorders Society's revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III) at 12 months postoperatively
Time Frame: 12 months after surgery
demonstrate statistically significant improvement in score of MDS-UPDRS III from Off stimulation/Off medication state to On stimulation/Off medication state at 12 months; MDS-UPDRS III ranges from 0 to 132, higher scores mean a worse outcome
12 months after surgery
change in PD-related quality of life(PDQ-39)
Time Frame: 12 months after surgery
demonstrate statistically significant improvement in score of PDQ-39 from baseline to 12 months;PDQ-39 was used to evaluate the improvement in quality of life, ranged from 0 to 156, higher scores mean a worse outcome.
12 months after surgery

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
change in the score of Gait and Fall Questionnaire (GFQ) at 3 months postoperatively
Time Frame: 3 months after surgery
demonstrate statistically significant improvement in score of GFQ from baseline to 3 months;GFQ range from 0 to 64, higher scores mean a worse outcome.
3 months after surgery
change in the score of Gait and Fall Questionnaire (GFQ) at 12 months postoperatively
Time Frame: 12 months after surgery
demonstrate statistically significant improvement in score of GFQ from baseline to 12 months; GFQ ranges from 0 to 64, higher scores mean a worse outcome.
12 months after surgery
change in severity of freezing of gait (New Freezing of Gait Questionnaire,NFOGQ) at 3 months postoperatively
Time Frame: 3 months after surgery
demonstrate statistically significant improvement in score of "New Freezing of Gait Questionnaire (NFOGQ)" from baseline to 3 months; NFOGQ is used to quantify freezing of gait severity, ranged from 0 to 30, higher scores mean a worse outcome.
3 months after surgery
change in severity of freezing of gait (New Freezing of Gait Questionnaire,NFOGQ) at 12 months postoperatively
Time Frame: 12 months after surgery
demonstrate statistically significant improvement in score of "New Freezing of Gait Questionnaire (NFOGQ)" from baseline to 12 months; NFOGQ is used to quantify freezing of gait severity, ranged from 0 to 30, higher scores mean a worse outcome.
12 months after surgery
Clinical Global Impression-Global Improvement (CGI-GI) at 3 months postoperatively
Time Frame: 3 months after surgery
to evaluate effectiveness on the basis of the physician's assessment, as well as on the basis of the patients' self-reported satisfaction. It is rated on a 7-point scale, range from 1(very much improved) through to 7 (very much worse)
3 months after surgery
Clinical Global Impression-Global Improvement (CGI-GI) at 12 months postoperatively
Time Frame: 12 months after surgery
to evaluate effectiveness on the basis of the physician's assessment, as well as on the basis of the patients' self-reported satisfaction. It is rated on a 7-point scale, range from 1(very much improved) through to 7 (very much worse)
12 months after surgery
change in the score of Berg Balance Scale(BBS) at 3 months postoperatively
Time Frame: 3 months after surgery
demonstrate statistically significant improvement in score of Berg Balance Scale(BBS) from baseline( Off medication state) to 3 months(On stimulation/Off medication state)； BBS ranged from 0 to 56, higher scores mean a better outcome.
3 months after surgery
change in the score of Berg Balance Scale(BBS) at 12 months postoperatively
Time Frame: 12 months after surgery
demonstrate statistically significant improvement in score of Berg Balance Scale(BBS) from Off stimulation/Off medication state to On stimulation/Off medication state at 12 months；BBS ranged from 0 to 56, higher scores mean a better outcome.
12 months after surgery

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
zhangyuqing

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Yuqing Zhang, MD, Capital Medical University- Xuanwu Hospital

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 5, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 30, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 4, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 5, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 14, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 11, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2020005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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