Study on Preliminary Safety and Efficacy of the ARC-IM Therapy to Alleviate Locomotor Deficits in People With Parkinson's Disease

Parkinson Disease Clinical Trial

— SPARKL  

Official title:

Study on Preliminary Safety and Efficacy of the ARC-IM Therapy to Alleviate Locomotor Deficits in People With Parkinson's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06295614
• Other study ID #: SPARKL
• Status: Recruiting
• Phase: N/A
• Start date: March 1, 2024
• Est. completion date: April 1, 2029

Study information

• Verified date: March 2024
• Source: Ecole Polytechnique Fédérale de Lausanne
• Contact: Jocelyne Bloch, MD
• Phone: +41 79 556 29 51
• Email: jocelyne.bloch[@]chuv.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical trial is to assess the preliminary safety and efficacy of the ARC-IM spinal cord stimulation therapy in alleviating locomotor deficits in individuals with Parkinson's disease. The ARC-IM Therapy employs epidural electrical stimulation (EES) to modulate leg muscle recruitment, with the aim of improving mobility deficits. The ultimate goal is to enhance the quality of life of people with Parkinson's disease.

Description:

The progression of Parkinson's Disease (PD) is often marked by the development of severe locomotor deficits, including gait impairments, which significantly affect patients' independence and are not effectively addressed by current treatments. The STIMO-PARKINSON (NCT04956770) clinical trial has shown promising results with epidural electrical stimulation (EES) in significantly reducing these locomotor deficits in Parkinson's Disease patients.

Building on these findings, the SPARKL clinical study aims to further this research. The SPARKL study aims to enroll six individuals with advanced Parkinson's Disease to assess the safety and efficacy of the novel ARC-IM Therapy. This new therapy has been designed to overcome previous technological limitations and facilitate its home-use.

This study will take place at the Lausanne University Hospital (CHUV, Switzerland). The total duration of the study is 4 years per participant. The study intervention consists of several phases preceded by pre-screening. The first year involves an intensive participation, consisting of the following phases: enrolment and baseline, surgical implantation of the stimulation device, a main study phase that includes stimulation configuration sessions and both in-clinic and at-home rehabilitation, and finally the home-use phase. This will be succeeded by 3 years of safety follow-up, during which the participant can use the stimulation device in their daily life, subject to investigator approval.

Throughout the study, the investigators will conduct assessments at various stages of each participant's journey in the study. These assessments will be used to assess the preliminary safety and efficacy of the ARC-IM therapy at alleviating locomotor deficits.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: April 1, 2029
• Est. primary completion date: April 1, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Typical form of Parkinson's Disease with III-V Hoehn-Yahr stage with standard therapy,

• Suffering from debilitating locomotor deficits, including gait impairments of either postural instability and/or freezing of gait, despite optimal medical management,

• 18 years of age or older,

• Able to understand and interact with the study team in French or English,

• Must use safe contraception for women of childbearing capacity,

• Must agree to comply in good faith with all conditions of the study and to attend all required study trainings and visits.

• Must provide and sign the study's Informed Consent prior to any study-related procedures.

Exclusion Criteria:

• Atypical forms of Parkinson's Disease (such as Multiple System Atrophy or Progressive Supranuclear Palsy),

• Secondary causes of gait problems independent of Parkinson's Disease,

• Inability to follow study procedures,

• Unstable or significant medical condition that is likely to interfere with study procedures or likely to confound study endpoint evaluations as determined by the Investigator,

• History of major psychiatric disorders or major neurocognitive disorder as considered by the Investigators in accordance with treating physician and treating neurologist,

• Major change in PD treatment planned until the end of the main study phase (such as Deep Brain Stimulation or dopamine-pump implantation),

• Diseases and conditions that would increase the morbidity and mortality of the implantation surgery,

• Spinal anatomical abnormalities precluding surgery,

• History of drug or alcohol abuse in the past 5 years,

• Life expectancy of less than 12 months,

• Pregnant or breast feeding,

• Intention to get pregnant during the course of the study,

• Indication requiring frequent Magnetic Resonance Imaging (MRI),

• Experimental treatment taken in the past 5 years,

• Participation in another interventional study,

• Enrolment of the investigator, his/her family members, employees, and other dependent persons.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Device:
• ARC-IM System implantation
Implantation of a stimulation lead on the lumbar level of the spinal cord and implantation of a neurostimulator in the abdominal region.

Locations

Country	Name	City	State
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne	Vaud

Sponsors (1)

Lead Sponsor	Collaborator
Ecole Polytechnique Fédérale de Lausanne

Country where clinical trial is conducted

Switzerland, 

References & Publications (16)

Bloem BR, Hausdorff JM, Visser JE, Giladi N. Falls and freezing of gait in Parkinson's disease: a review of two interconnected, episodic phenomena. Mov Disord. 2004 Aug;19(8):871-84. doi: 10.1002/mds.20115. — View Citation

Capogrosso M, Wagner FB, Gandar J, Moraud EM, Wenger N, Milekovic T, Shkorbatova P, Pavlova N, Musienko P, Bezard E, Bloch J, Courtine G. Configuration of electrical spinal cord stimulation through real-time processing of gait kinematics. Nat Protoc. 2018 Sep;13(9):2031-2061. doi: 10.1038/s41596-018-0030-9. — View Citation

Capogrosso M, Wenger N, Raspopovic S, Musienko P, Beauparlant J, Bassi Luciani L, Courtine G, Micera S. A computational model for epidural electrical stimulation of spinal sensorimotor circuits. J Neurosci. 2013 Dec 4;33(49):19326-40. doi: 10.1523/JNEUROSCI.1688-13.2013. — View Citation

Hofstoetter US, Perret I, Bayart A, Lackner P, Binder H, Freundl B, Minassian K. Spinal motor mapping by epidural stimulation of lumbosacral posterior roots in humans. iScience. 2020 Dec 11;24(1):101930. doi: 10.1016/j.isci.2020.101930. eCollection 2021 Jan 22. — View Citation

Maetzler W, Nieuwhof F, Hasmann SE, Bloem BR. Emerging therapies for gait disability and balance impairment: promises and pitfalls. Mov Disord. 2013 Sep 15;28(11):1576-86. doi: 10.1002/mds.25682. — View Citation

Milekovic T, Moraud EM, Macellari N, Moerman C, Raschella F, Sun S, Perich MG, Varescon C, Demesmaeker R, Bruel A, Bole-Feysot LN, Schiavone G, Pirondini E, YunLong C, Hao L, Galvez A, Hernandez-Charpak SD, Dumont G, Ravier J, Le Goff-Mignardot CG, Mignardot JB, Carparelli G, Harte C, Hankov N, Aureli V, Watrin A, Lambert H, Borton D, Laurens J, Vollenweider I, Borgognon S, Bourre F, Goillandeau M, Ko WKD, Petit L, Li Q, Buschman R, Buse N, Yaroshinsky M, Ledoux JB, Becce F, Jimenez MC, Bally JF, Denison T, Guehl D, Ijspeert A, Capogrosso M, Squair JW, Asboth L, Starr PA, Wang DD, Lacour SP, Micera S, Qin C, Bloch J, Bezard E, Courtine G. A spinal cord neuroprosthesis for locomotor deficits due to Parkinson's disease. Nat Med. 2023 Nov;29(11):2854-2865. doi: 10.1038/s41591-023-02584-1. Epub 2023 Nov 6. — View Citation

Moraud EM, Capogrosso M, Formento E, Wenger N, DiGiovanna J, Courtine G, Micera S. Mechanisms Underlying the Neuromodulation of Spinal Circuits for Correcting Gait and Balance Deficits after Spinal Cord Injury. Neuron. 2016 Feb 17;89(4):814-28. doi: 10.1016/j.neuron.2016.01.009. Epub 2016 Feb 4. — View Citation

Nicolelis MA, Fuentes R, Petersson P, Thevathasan W, Brown P. Spinal cord stimulation failed to relieve akinesia or restore locomotion in Parkinson disease. Neurology. 2010 Oct 19;75(16):1484; author reply 1484-5. doi: 10.1212/WNL.0b013e3181f46f10. No abstract available. — View Citation

Nishioka K, Nakajima M. Beneficial Therapeutic Effects of Spinal Cord Stimulation in Advanced Cases of Parkinson's Disease With Intractable Chronic Pain: A Case Series. Neuromodulation. 2015 Dec;18(8):751-3. doi: 10.1111/ner.12315. Epub 2015 Jun 5. — View Citation

Pinto de Souza C, Hamani C, Oliveira Souza C, Lopez Contreras WO, Dos Santos Ghilardi MG, Cury RG, Reis Barbosa E, Jacobsen Teixeira M, Talamoni Fonoff E. Spinal cord stimulation improves gait in patients with Parkinson's disease previously treated with deep brain stimulation. Mov Disord. 2017 Feb;32(2):278-282. doi: 10.1002/mds.26850. Epub 2016 Nov 10. — View Citation

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. — View Citation

Rowald A, Komi S, Demesmaeker R, Baaklini E, Hernandez-Charpak SD, Paoles E, Montanaro H, Cassara A, Becce F, Lloyd B, Newton T, Ravier J, Kinany N, D'Ercole M, Paley A, Hankov N, Varescon C, McCracken L, Vat M, Caban M, Watrin A, Jacquet C, Bole-Feysot L, Harte C, Lorach H, Galvez A, Tschopp M, Herrmann N, Wacker M, Geernaert L, Fodor I, Radevich V, Van Den Keybus K, Eberle G, Pralong E, Roulet M, Ledoux JB, Fornari E, Mandija S, Mattera L, Martuzzi R, Nazarian B, Benkler S, Callegari S, Greiner N, Fuhrer B, Froeling M, Buse N, Denison T, Buschman R, Wende C, Ganty D, Bakker J, Delattre V, Lambert H, Minassian K, van den Berg CAT, Kavounoudias A, Micera S, Van De Ville D, Barraud Q, Kurt E, Kuster N, Neufeld E, Capogrosso M, Asboth L, Wagner FB, Bloch J, Courtine G. Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis. Nat Med. 2022 Feb;28(2):260-271. doi: 10.1038/s41591-021-01663-5. Epub 2022 Feb 7. — View Citation

Schaafsma JD, Giladi N, Balash Y, Bartels AL, Gurevich T, Hausdorff JM. Gait dynamics in Parkinson's disease: relationship to Parkinsonian features, falls and response to levodopa. J Neurol Sci. 2003 Aug 15;212(1-2):47-53. doi: 10.1016/s0022-510x(03)00104-7. — View Citation

van den Brand R, Heutschi J, Barraud Q, DiGiovanna J, Bartholdi K, Huerlimann M, Friedli L, Vollenweider I, Moraud EM, Duis S, Dominici N, Micera S, Musienko P, Courtine G. Restoring voluntary control of locomotion after paralyzing spinal cord injury. Science. 2012 Jun 1;336(6085):1182-5. doi: 10.1126/science.1217416. — View Citation

Wagner FB, Mignardot JB, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M, Rowald A, Seanez I, Caban M, Pirondini E, Vat M, McCracken LA, Heimgartner R, Fodor I, Watrin A, Seguin P, Paoles E, Van Den Keybus K, Eberle G, Schurch B, Pralong E, Becce F, Prior J, Buse N, Buschman R, Neufeld E, Kuster N, Carda S, von Zitzewitz J, Delattre V, Denison T, Lambert H, Minassian K, Bloch J, Courtine G. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018 Nov;563(7729):65-71. doi: 10.1038/s41586-018-0649-2. Epub 2018 Oct 31. — View Citation

Yakovenko S, Mushahwar V, VanderHorst V, Holstege G, Prochazka A. Spatiotemporal activation of lumbosacral motoneurons in the locomotor step cycle. J Neurophysiol. 2002 Mar;87(3):1542-53. doi: 10.1152/jn.00479.2001. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Nerve conduction studies (NCS)	To assess status of peripheral nervous system. Measurement tool: electrical activity in the nerve (mV)	Baseline assessments
Other	Somato-sensory evoked potential (SSEP)	To assess the transmission of electrical activity from a touch stimulation. Measurement tool: electrical activity in the nerve (mV)	Short-term assessments (~1 month post-surgery)
Other	Cortical signal recording	To assess changes in brain activity patterns. Measurement tool: electrical activity in the brain (mV)	After surgery, until 18 weeks post-surgery
Other	Kinematic analysis in different therapeutic conditions	Gait circuit to assess gait kinematic changes. Measurement tool: changes in position and orientation of the body through sensors (mm)	After surgery, until 18 weeks post-surgery
Other	Muscle analysis in different therapeutic conditions	Gait circuit to assess muscle activity change. Measurement tool: muscle activity through sensors (mV)	After surgery, until 18 weeks post-surgery
Primary	Occurrence of serious adverse events and adverse events that are deemed related or possibly related to the study procedures or to the investigational system.	Assess the safety of the ARC-IM Therapy at alleviating locomotor deficits in people with Parkinson's Disease.	From enrollment until end of safety follow-up phase (4 years)
Secondary	10-meter walk test	To assess gait speed. Measurement tool: time (s)	Baseline (before surgery), Short-Term assessments (~1 month post-surgery) and Follow-Up assessments (~4 & 11 months post-surgery)
Secondary	6-minute walk test	To assess endurance. Measurement tool: distance (m)	Baseline (before surgery), Short-Term assessments (~1 month post-surgery) and Follow-Up assessments (~4 & 11 months post-surgery)
Secondary	Timed up and Go and its cognitive version	To assess freezing of gait prevalence. Measurement tool: time (s)	Baseline (before surgery), Short-Term assessments (~1 month post-surgery) and Follow-Up assessments (~4 & 11 months post-surgery)
Secondary	Freezing of gait circuit	To assess freezing of gait prevalence. Measurement tool: time (s)	Baseline (before surgery), Short-Term assessments (~1 month post-surgery) and Follow-Up assessments (~4 & 11 months post-surgery)
Secondary	Kinematic analysis	Gait circuit to assess gait kinematic. Measurement tool: changes in position and orientation of the body through sensors (mm)	Baseline (before surgery), Short-Term assessments (~1 month post-surgery) and Follow-Up assessments (~4 & 11 months post-surgery)
Secondary	Muscle analysis	Gait circuit to assess muscle activity. Measurement tool: muscle activity through sensors (mV)	Baseline (before surgery), Short-Term assessments (~1 month post-surgery) and Follow-Up assessments (~4 & 11 months post-surgery)
Secondary	Mini Balance Evaluation Systems Test (mini-BESTest)	4-item test to assess balance. Measurement tool: total score	Baseline (before surgery), Short-Term assessments (~1 month post-surgery) and Follow-Up assessments (~4 & 11 months post-surgery)
Secondary	Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III	19 item-test to assess the course of Parkinson's Disease. Measurement tool: total score from 0 up to 132. Low score means a better outcome.	Baseline (before surgery), Short-Term assessments (~1 month post-surgery) and Follow-Up assessments (~4 & 11 months post-surgery)
Secondary	King's Parkinson's disease Pain Scale (KPPS)	7-item questionnaire to assess daily life performance. Measurement tool: total score 0 up to 168. Low score means a better outcome.	Baseline (before surgery), Short-Term assessments (~1 month post-surgery) and Follow-Up assessments (~4 & 11 months post-surgery)
Secondary	The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IA & IV Part I, II & IV.	3-part questionnaire to assess daily life performance. Measurement tool: total score from 0 up to 128. Low score means a better outcome.	Baseline (before surgery), Short-Term assessments (~1 month post-surgery) and Follow-Up assessments (~4 & 11 months post-surgery)
Secondary	Parkinson's Disease Questionnaire-39 (PDQ-39)	39-item questionnaire to assess daily life performance. Measurement tool: total score from 0 up to 100. Low score means a better outcome.	Monthly, from the start of the study until the end of the home-use phase (~12 months)
Secondary	Activities specific Balance Confidence Questionnaire (ABC-Q)	16-item questionnaire to assess daily life performance. Measurement tool: total score from 0 up to 100. High score means a better outcome.	Monthly, from the start of the study until the end of the home-use phase (~12 months)
Secondary	The Freezing of Gait Questionnaire (FOG-Q)	6-item questionnaire to assess daily life performance. Measurement tool: total score 0 up to 24. High score means a better outcome.	Monthly, from the start of the study until the end of the home-use phase (~12 months)
Secondary	Home-use kinematic monitoring	To assess gait pattern in ecological environment. Measurement tool: changes in position and orientation of the feet through sensors placed on shoes (mm)	Weekly, from the start of the study until the end of the home-use phase (~12 months)
Secondary	Daily falls tracking	To assess daily falls. Measurement tool: number of falls	Weekly, from the start of the study until the end of the home-use phase (~12 months)
Secondary	Satisfaction questionnaire	16-item questionnaire to collect feedback from the therapy. Measurement tool: total score from 0 up to 100.	Monthly, from the Short-Term assessments (~1 month post-surgery) until the end of the home-use phase (~12 months)
Secondary	User Evaluation of Satisfaction with technology (QUEST 2.0)	12-item questionnaire to assess usability of the therapy. Measurement tool: total score from 12 up to 60. Low score means a better outcome.	Follow-Up assessments (~4 & 11 months post-surgery)
Secondary	System Usability Scale (SUS)	Questionnaire to assess usability of the therapy. Measurement tool: total score from 0 to 100. High score means a better outcome.	Follow-Up assessments (~4 & 11 months post-surgery)