SCP-FOG: Combined Deep Brain Stimulation in Parkinson's Disease

Sponsor

University Hospital, Toulouse (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05415774

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Device: 1 : S-C1-C2 Device: 2 : S-C2-C1 Device: 3 : C1 - S - C2 Device: 4 : C1 -C2 - S Device: 5 : C2 - S - C1 Device: 6 : C2 - C1 - S	N/A

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:

One month of S-stimulation (130hz, STN).
One month of C1- stimulation;
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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Single center, randomized, three one-month periods, six sequences, cross-over, double blind, study to evaluate the effect of 2 innovative settings of DBS combining the stimulation of STN and SNr, vs. a standard (S) stimulation, on FoG, in PD patients with DBS with severe FoG. the sequence of different stimulation parameters will be randomized and not the treatment Each patient receives the three treatments (S, C1 and C2)Single center, randomized, three one-month periods, six sequences, cross-over, double blind, study to evaluate the effect of 2 innovative settings of DBS combining the stimulation of STN and SNr, vs. a standard (S) stimulation, on FoG, in PD patients with DBS with severe FoG. the sequence of different stimulation parameters will be randomized and not the treatment Each patient receives the three treatments (S, C1 and C2)

Masking:

Double (Participant, Investigator)

Primary Purpose:

Other

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: S Stimulation Standard STN DBS defined as high frequency at 130Hz stimulation	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
Experimental: C1 Stimulation Combined high frequency stimulation of the STN and SNr using an interleaved pulses at 125Hz	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
Experimental: C2 Stimulation Combined low frequency stimulation of the SNr at 60Hz and high frequency stimulation of the STN	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

Arm

Intervention/Treatment

Active Comparator: S Stimulation

Standard STN DBS defined as high frequency at 130Hz stimulation

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

Device: 3 : C1 - S - C2

Device: 4 : C1 -C2 - S

Device: 5 : C2 - S - C1

Device: 6 : C2 - C1 - S

Experimental: C1 Stimulation

Combined high frequency stimulation of the STN and SNr using an interleaved pulses at 125Hz

Device: 1 : S-C1-C2

Device: 2 : S-C2-C1

Device: 3 : C1 - S - C2

Device: 4 : C1 -C2 - S

Device: 5 : C2 - S - C1

Device: 6 : C2 - C1 - S

Experimental: C2 Stimulation

Combined low frequency stimulation of the SNr at 60Hz and high frequency stimulation of the STN

Device: 1 : S-C1-C2

Device: 2 : S-C2-C1

Device: 3 : C1 - S - C2

Device: 4 : C1 -C2 - S

Device: 5 : C2 - S - C1

Device: 6 : C2 - C1 - S

Outcome Measures

Primary Outcome Measures

Score change of the " New freezing of gait questionnaire " [ONE MONTH AFTER INCLUSION]
the score change of the means of the New freezing of gait questionnaire at the end of each combined C1 and C2 stimulation, compared to S stimulation at one month of each period. The NFOG-Q is a clinician rated instrument used to evaluate FOG severity in patients with PD, unrelated to falls. Item responses use a 5-point scale ranging from 0 (absence of symptom) to 4 (severe). Total score ranges from 0 to 28; higher scores correspond to more severe FOG. Answers are based on experience over the past week or overall FOG during an entire day.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Idiopathic PD defined as by the MDS Criteria ;
Patients submitted to STN-DBS, for at least 6 months;
Patients with STN-DBS at 130Hz;
Patients with a troublesome FoG according to the "NFOG-Q", Part II Item II ≥ 2 or Part III Item 7 ≥ 2;
Mini Mental State (MMS) ≥ 25 ;
Ventral contact of electrodes implanted in the SNr (according to analysis of activated tissue volume models (VTA));
Patients with stable parkinsonian stimulation parameters and anti-parkinsonian treatments for one month before the inclusion visit;
Patients with H/Y stage ≤ 3 in the Med ON/Stim On condition (at 130Hz, S-stimulation);

Exclusion Criteria:

Patient with atypical Parkinsonian syndrome;
Patient with severe FoG before DBS, i.e. MDS-UPDRS item 2.13 in Med ON ≥2 or MDS-UPDRS item 3.11 ≥2 in Med On;
Patient whose antiparkinsonian treatments were modified during the last month before inclusion;
Patient with H&Y stage ≥4 in Med On/Stim On (at 130Hz, S-stimulation) ;

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University Hospital, Toulouse

Investigators

Principal Investigator: Margherita FABBRI, MD, University Hospital, Toulouse

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University Hospital, Toulouse

ClinicalTrials.gov Identifier:

NCT05415774

Other Study ID Numbers:

RC31/21/0609

First Posted:

Jun 13, 2022

Last Update Posted:

Jun 13, 2022

Last Verified:

Jun 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by University Hospital, Toulouse

freezing of gait

deep brain stimulation

combined deep brain stimulation

Additional relevant MeSH terms:

Parkinson Disease

Study Results

No Results Posted as of Jun 13, 2022