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

December 8, 2023 updated by: University Hospital, Toulouse

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • 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 Contact

Study Locations

  • France
      • Toulouse, France, 31000
        • Uh Toulouse

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 to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. Patient with atypical Parkinsonian syndrome;
  2. 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;
  3. Patient whose antiparkinsonian treatments were modified during the last month before inclusion;
  4. Patient with H&Y stage ≥4 in Med On/Stim On (at 130Hz, S-stimulation) ;

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: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Score change of the " New freezing of gait questionnaire "
Time Frame: 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.
ONE MONTH AFTER INCLUSION

Collaborators and Investigators

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

Sponsor

University Hospital, Toulouse

Investigators

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

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)

September 9, 2022

Primary Completion (Actual)

May 10, 2023

Study Completion (Actual)

May 10, 2023

Study Registration Dates

First Submitted

June 8, 2022

First Submitted That Met QC Criteria

June 8, 2022

First Posted (Actual)

June 13, 2022

Study Record Updates

Last Update Posted (Actual)

December 11, 2023

Last Update Submitted That Met QC Criteria

December 8, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC31/21/0609

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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