Study on Feasibility of Targeted Epidural Spinal Stimulation (TESS) to Improve Mobility in Patients With Parkinson's Disease (STIMO-PARK)

STIMO-PARKINSON: Study on Feasibility of Targeted Epidural Spinal Stimulation (TESS) to Improve Mobility in Patients With Parkinson's Disease

The purpose of the STIMO-PARKINSON study is to evaluate the safety and preliminary efficacy of Targeted Epidural Spinal Stimulation (TESS) system to induce modulation in leg muscle recruitment in patients with advanced Parkinson's disease, and its capacity to improve key gait and balance deficits when employed in the context of a rehabilitation process of 3 to 5 months.

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Procedure: Implantation surgery

Detailed Description

The study intervention consists of 7 phases preceded by pre-screening:

• enrolment and eligibility
• baseline
• surgery
• main phase of the study
• home-use
• end of main study phase
• (optional and conditional): 3 years follow-up

At baseline, general information and Parkinson related medical history are collected. Clinical evaluations are also completed without and with current therapy, (i.e. NO(MED+DBS), and MED+DBS conditions). Finally, quality of life questionnaires are collected for the patient as well as expectations questionnaires for the physiotherapists involved in the study.

The main phase of the study consists of:

• Stimulation configuration sessions during which TESS protocols will be setup and optimized. This procedure aims to configure the spatial and temporal parameters of TESS that will recruit specific muscle groups. Specific TESS protocols will be configured for various motor tasks which will be used during the rehabilitation phase and clinical evaluations.
• TESS-supported rehabilitation sessions during which patients will undergo an in-clinic rehabilitation training regime supported by TESS.

• Evaluation sessions during which four clinical evaluation sessions will take place focusing on assessment of locomotion, balance and PD related deficits. The tests will be done when patients are:

  (i) in NO(MED+DBS) condition (without any therapy, i.e. without medication and DBS OFF) (ii) in MED+DBS condition (the patient's standard therapeutical condition, i.e. usual medication dose and DBS ON) (iii) in TESS+MED condition (usual medication dose, TESS ON, DBS OFF) (iv) in TESS+MED+DBS condition (usual medication dose, TESS ON, DBS ON)

Participants are allowed to use the investigational system independently if deemed safe and beneficial as assessed by the Principal Investigator (Home-Use Phase).

One year after patient enrolment, the patient will come for follow up visits where he will again perform an evaluation session for each therapy condition as described above, to evaluate the long-term evolution.

If the therapy has been safe and beneficial, they can extend their study participation by entering the Follow-Up period of 3 years.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jocelyne Bloch, MD; Phone Number: 0041795562951; Email: jocelyne.bloch@chuv.ch
• Study Contact Backup: Name: John-Paul Miroz; Phone Number: 0041795568979; Email: John-Paul.Miroz@chuv.ch

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • CHUV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Idiopathic Parkinson's disease with III-IV Hoehn-Yahr stage, exhibiting severe gait difficulties and postural instability
• With Medtronic DBS implant and receiving medication for Parkinson's disease
• Aged 18 to 80 years
• Stable medical, physical and psychological condition as considered by the Investigators in accordance with treating physician and treating neurologist.
• Must agree to comply in good faith with all conditions of the study and to attend all required study training and visit
• Must provide and sign the study's Informed Consent prior to any study-related procedures

Exclusion Criteria:

• Severe or chronic medical disorder pre-existing PD diagnosis affecting rehabilitation
• Active oncological disease requiring heavy treatments and frequent MRI controls
• Having an implanted device that is active (e.g., pacemaker, implantable cardiac defibrillator) whose interference with the investigational system's neurostimulator (Activa RC) is not confirmed safe by the CE-mark of the device, or having an indication that might lead to implantation of such device
• Inability to follow study procedures, e.g. due to language problems, psychological disorders, dementia as considered by the Investigators in accordance with treating physician and treating neurologist
• Hematological disorders with an increased risk of hemorrhagic event during surgical interventions
• Life expectancy of less than 12 months
• Pregnant or breast feeding
• Participation in another interventional study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Rehabilitation supported by TESS; Patient will be asked to come to the hospital for three types of patient sessions: Stimulation configuration sessions: TESS protocols will be setup and optimized during this phase. Duration: minimum 4 sessions over 2 weeks, maximum 20 sessions over a month. In addition, some sessions at a free frequency as needed during rehabilitation will be programed (maximum once a week).; TESS-supported rehabilitation sessions: Patients will undergo an in-clinic rehabilitation training regime supported by TESS. Duration: 24 sessions spread over minimum three months and maximum five months; Pre- and post-rehabilitation evaluation sessions: four clinical evaluation sessions will take place focusing on assessment of locomotion, balance and PD related deficits.

Procedure: Implantation surgery; The intervention involves the implantation of: a neurostimulator: the Activa® RC from Medtronic; a stimulation electrode paddle array: the Specify™ SureScan® 5-6-5 from Medtronic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurence of all SAEs and AEs deemed or related to study procedure or to the study investigational system	Evaluate the safety of TESS at supporting locomotor rehabilitation in patients with Parkinson's Disease	Through study completion, an average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EMG measurements of muscle recruitment in response to stimulation of increasing amplitudes for different contact configurations	Assess the preliminary efficacy outcome of TESS to induce modulations in muscle recruitment selectivity by measuring the EMG response to iterative stimulation pulses of increasing amplitude for different contact configurations	At baseline and during the 5-month TESS-supported rehabilitation phase
Maximum voluntary contraction (MVC) of single joints	Assess the preliminary efficacy of TESS on motor performance through changes in single joint leg muscle strength and fatigue	At baseline and during the 5-month TESS-supported rehabilitation phase
Muscle Fatigue Test	Measure the time the patient can maintain a certain percentage of his MVC measured in the MED+DBS condition. This is used to assess the preliminary efficacy of TESS on motor performance through changes in single joint leg muscle strength and fatigue	At baseline and during the 5-month TESS-supported rehabilitation phase
10-meter walk test	Assess the preliminary efficacy of TESS on motor performance through changes in gait speed and endurance	At baseline and during the 5-month TESS-supported rehabilitation phase
6 minute walk test	Assess the preliminary efficacy of TESS on motor performance through changes in gait speed and endurance	At baseline and during the 5-month TESS-supported rehabilitation phase
Timed up and Go test and its cognitive version, as custom-made FOG circuit	Assess the preliminary efficacy of TESS for alleviating deficits specific to PD related to freezing of gait (FOG)	At baseline and during the 5-month TESS-supported rehabilitation phase
Kinematic analysis	Assess the preliminary efficacy of TESS for alleviating deficits specific to PD related to posture using motion sensors acquisition system	At baseline and during the 5-month TESS-supported rehabilitation phase
Mini Balance Evaluation Systems Test (mini-BESTest)	Assess the preliminary efficacy of TESS for alleviating deficits specific to PD related to balance	At baseline and during the 5-month TESS-supported rehabilitation phase
Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	Assess the preliminary efficacy of TESS for alleviating deficits specific to PD related to motor and non-motor functions. Higher scores indicate greater impact of Parkinson's disease symptoms	At baseline and during the 5-month TESS-supported rehabilitation phase

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortical (EEG) and subcortical signals (LFP from the subthalamic nucleus)	Assess changes in brain activity patterns induced by TESS-supported physical training to get insight into the effects of TESS on brain dynamics. This will be done in the four therapy conditions for rest, for single-joint leg tasks and, if results are encouraging, for gait	At baseline and during the 5-month TESS-supported rehabilitation phase
Quality of life questionnaire PDQ-39	Evaluate the effect of TESS-supported rehabilitation on quality of life of patients through the Parkinson's Disease Questionnaire (PDQ-39). The score ranges from 0 to 100, lower scores reflect better quality of life	At baseline and during the 5-month TESS-supported rehabilitation phase
Quality of life questionnaire ABC-Q	Evaluate the effect of TESS-supported rehabilitation on quality of life of patients through the Activities-specific Balance Confidence Scale (ABC-Q). The score ranges from 0% to 100%, higher score reflects higher level of physical functioning	At baseline and during the 5-month TESS-supported rehabilitation phase
Quality of life questionnaire FOG-Q	Evaluate the effect of TESS-supported rehabilitation on quality of life of patients through the Freezing of Gait Questionnaire (FOG-Q). The score ranges from 0 to 24, higher scores correspond to more severe FOG	At baseline and during the 5-month TESS-supported rehabilitation phase
Quality of life questionnaire KPPS	Evaluate the effect of TESS-supported rehabilitation on quality of life of patients through King's Parkinson's disease pain scale. The score ranges from 0 to 168, higher scores correspond to higher pain.	At baseline and during the 5-month TESS-supported rehabilitation phase
Therapist expectations and learnings questionnaire	Obtain information concerning the perceived efficacy of TESS-supported rehabilitation for Parkinson's patients and whether they would recommend tis new therapy for general clinical practice	At baseline (before the patient is implanted) and at the time of study completion

Collaborators and Investigators

• Sponsor: Jocelyne Bloch
• Collaborators: Ecole Polytechnique Fédérale de Lausanne
• Investigators: Principal Investigator: Jocelyne Bloch, MD, CHUV

Publications and helpful links

General Publications

• Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA. Spinal cord stimulation restores locomotion in animal models of Parkinson's disease. Science. 2009 Mar 20;323(5921):1578-82. doi: 10.1126/science.1164901.
• Santana MB, Halje P, Simplicio H, Richter U, Freire MAM, Petersson P, Fuentes R, Nicolelis MAL. Spinal cord stimulation alleviates motor deficits in a primate model of Parkinson disease. Neuron. 2014 Nov 19;84(4):716-722. doi: 10.1016/j.neuron.2014.08.061. Epub 2014 Oct 30.
• Yadav AP, Nicolelis MAL. Electrical stimulation of the dorsal columns of the spinal cord for Parkinson's disease. Mov Disord. 2017 Jun;32(6):820-832. doi: 10.1002/mds.27033. Epub 2017 May 12.
• Courtine G, Gerasimenko Y, van den Brand R, Yew A, Musienko P, Zhong H, Song B, Ao Y, Ichiyama RM, Lavrov I, Roy RR, Sofroniew MV, Edgerton VR. Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nat Neurosci. 2009 Oct;12(10):1333-42. doi: 10.1038/nn.2401. Epub 2009 Sep 20.
• Capogrosso M, Milekovic T, Borton D, Wagner F, Moraud EM, Mignardot JB, Buse N, Gandar J, Barraud Q, Xing D, Rey E, Duis S, Jianzhong Y, Ko WK, Li Q, Detemple P, Denison T, Micera S, Bezard E, Bloch J, Courtine G. A brain-spine interface alleviating gait deficits after spinal cord injury in primates. Nature. 2016 Nov 10;539(7628):284-288. doi: 10.1038/nature20118.
• Strauss I, Kalia SK, Lozano AM. Where are we with surgical therapies for Parkinson's disease? Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1:S187-91. doi: 10.1016/S1353-8020(13)70044-0.
• Courtine G, Bloch J. Defining ecological strategies in neuroprosthetics. Neuron. 2015 Apr 8;86(1):29-33. doi: 10.1016/j.neuron.2015.02.039.
• Cai Y, Reddy RD, Varshney V, Chakravarthy KV. Spinal cord stimulation in Parkinson's disease: a review of the preclinical and clinical data and future prospects. Bioelectron Med. 2020 Mar 16;6:5. doi: 10.1186/s42234-020-00041-9. eCollection 2020.
• Prasad S, Aguirre-Padilla DH, Poon YY, Kalsi-Ryan S, Lozano AM, Fasano A. Spinal Cord Stimulation for Very Advanced Parkinson's Disease: A 1-Year Prospective Trial. Mov Disord. 2020 Jun;35(6):1082-1083. doi: 10.1002/mds.28065. Epub 2020 Apr 20. No abstract available.
• Cury RG, Carra RB, Capato TTC, Teixeira MJ, Barbosa ER. Spinal Cord Stimulation for Parkinson's Disease: Dynamic Habituation as a Mechanism of Failure? Mov Disord. 2020 Oct;35(10):1882-1883. doi: 10.1002/mds.28271. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2021
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: May 31, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (Actual): July 9, 2021

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: DBS; Spinal Cord Stimulation System
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: STIMO-PARK2021

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