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

Multiple System Atrophy, Parkinson Variant (Disorder) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04617873
• Other study ID #: 2020005
• Status: Recruiting
• Phase: N/A
• Start date: January 5, 2021
• Est. completion date: January 1, 2024

Study information

• Verified date: January 2021
• Source: Xuanwu Hospital, Beijing
• Contact: Jiping Li, MD
• Phone: 8610-83198899-8630
• Email: yhljp89[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 1, 2024
• Est. primary completion date: January 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Atrophy
• Multiple System Atrophy
• Multiple System Atrophy, Parkinson Variant (Disorder)
• Parkinsonian Disorders
• Shy-Drager Syndrome

Intervention

Procedure:
• Bilateral STN-DBS and T10-T12 SCS
simultaneous stimulation of bilaterally-STN-DBS combined with spinal cord stimulation

Locations

Country	Name	City	State
China	Capital Medical University of Xuanwu Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
zhangyuqing

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in motor examination( Movement Disorders Society's revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III) at 3 months postoperatively	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
Primary	change in motor examination( Movement Disorders Society's revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III) at 12 months postoperatively	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
Primary	change in PD-related quality of life(PDQ-39)	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	change in the score of Gait and Fall Questionnaire (GFQ) at 3 months postoperatively	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
Secondary	change in the score of Gait and Fall Questionnaire (GFQ) at 12 months postoperatively	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
Secondary	change in severity of freezing of gait (New Freezing of Gait Questionnaire,NFOGQ) at 3 months postoperatively	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
Secondary	change in severity of freezing of gait (New Freezing of Gait Questionnaire,NFOGQ) at 12 months postoperatively	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
Secondary	Clinical Global Impression-Global Improvement (CGI-GI) at 3 months postoperatively	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
Secondary	Clinical Global Impression-Global Improvement (CGI-GI) at 12 months postoperatively	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
Secondary	change in the score of Berg Balance Scale(BBS) at 3 months postoperatively	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
Secondary	change in the score of Berg Balance Scale(BBS) at 12 months postoperatively	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