NCT05415774

Combined Deep Brain Stimulation in Parkinson's Disease

Combined Deep Brain Stimulation of the Substantia Nigra Pars Reticulata and of the Subthalamic Nucleus for Unresponsive Freezing of Gait in Parkinson's Disease: a Pilot Cross-over Study

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: University Hospital, Toulouse · Academic / Other
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

The study is a pilot study on Parkinson's disease patients to evaluate Combined deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus for unresponsive freezing of gait.

Detailed description

One of the most challenging and unresolved problems in Parkinson's disease (PD) is the treatment of gait disorders, unresponsive to dopaminergic medication. Additionally, PD patients suffering from severe/unresponsive gait disorders are not considered good candidates for subthalamic nucleus deep brain stimulation (STN-DBS). Currently, there are no specific therapies to treat gait disorders in PD with an insufficient response to dopaminergic treatment. Furthermore, axial symptoms develop during disease progression even in operated patients. Axial symptoms are often one of the main causes of disability. There is evidence suggesting that low-frequency (LF) stimulation of the ventral area of the STN can improve axial symptoms. At the same time, the substantia nigra pars reticulata (SNr) is one of the most important output centers of the basal ganglia and is integrated within the locomotor control systems. Neurons within the SNr may act as high-frequency (HF) pacemakers, disrupting normal behavior downstream in the circuit. HF-STN in combination with LF or HF-SNr stimulation have been shown some beneficial effect on freezing of gait (FoG) among PD patients who had FoG unresponsive to dopaminergic therapy. However, only small pilot trials and case series have been investigated this strategy and evidences are scarce. The aim of this study is to evaluate the effect of combined (C) stimulation of the STN and SNr on FoG if compared to standard (S) stimulation of the STN at 130 Hz, over one month. Based on previous literature evidence as primary aim the respective effect of two setting of C-stimulation will be separately assessed: a) C1- stimulation, with HF stimulation of the STN and SNr using a 'interleaved pulses' at 125 Hz vs. S- stimulation, over one month; b) C2-stimulation with LF stimulation of the SNr at 60Hz and HF stimulation of the STN vs. S- stimulation, over one month. Other objectives are to evaluate the: * Tolerance of combined stimulation (STN + SNr) through the collection of adverse events (AEs) * Development of psychic events such as the presence of depression or dysphoria * Effect of C (C1 and C2) -stimulation on walking disorders and other axial symptoms if compared vs. the S-stimulation. * Effect of C (C1 and C2) -stimulation on PD's motor symptoms and motor complications if compared vs. the S-stimulation. * Effect of C (C1 and C2) -stimulation on sleep quality if compared vs. the S-stimulation. Each patient will have the 3 types of stimulation: 1. One month of S-stimulation (130hz, STN). 2. One month of C1- stimulation; 3. One month of C2- stimulation; Stimulation setting order will be randomly assigned. Minimal dopaminergic treatment adjustment will be allowed to minimize the drop-out rate (± 100 mg of levodopa equivalent daily dose) and registered

Conditions

• Parkinson Disease

Interventions

Type	Name	Description
DEVICE	1 : S-C1-C2	Deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus according to the order of randomisation (see intervention name) : * Standard stimulation * 125Hz at both STN and SNr for C1, * 125Hz for STN and 60 for SNr for C2
DEVICE	2 : S-C2-C1	Deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus according to the order of randomisation (see intervention name) : * Standard stimulation * 125Hz at both STN and SNr for C1, * 125Hz for STN and 60 for SNr for C2
DEVICE	3 : C1 - S - C2	Deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus according to the order of randomisation (see intervention name) : * Standard stimulation * 125Hz at both STN and SNr for C1, * 125Hz for STN and 60 for SNr for C2
DEVICE	4 : C1 -C2 - S	Deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus according to the order of randomisation (see intervention name) : * Standard stimulation * 125Hz at both STN and SNr for C1, * 125Hz for STN and 60 for SNr for C2
DEVICE	5 : C2 - S - C1	Deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus according to the order of randomisation (see intervention name) : * Standard stimulation * 125Hz at both STN and SNr for C1, * 125Hz for STN and 60 for SNr for C2
DEVICE	6 : C2 - C1 - S	Deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus according to the order of randomisation (see intervention name) : * Standard stimulation * 125Hz at both STN and SNr for C1, * 125Hz for STN and 60 for SNr for C2

Timeline

• Start date: 2022-09-09
• Primary completion: 2023-05-10
• Completion: 2023-05-10
• First posted: 2022-06-13
• Last updated: 2025-11-28

Locations

1 site across 1 country: France