Deep Brain Stimulation of the Lateral Hypothalamus to Augment Motor Function of Patients With Spinal Cord Injury

NCT04965727 | Unknown DMC

• 1 other identifier: HoT-DBS2021
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate safety of Deep Brain Stimulation (DBS) of the lateral hypothalamus (LH) and whether the use of DBS can increase motor performance in patients with chronic spinal cord injury (SCI). The hypothesis, based on preclinical findings, is that DBS of the lateral hypothalamus can acutely augment leg motor function after SCI, and that the use of lateral hypothalamus DBS can be an adjunct during rehabilitation to promote recovery and long-term neuroplasticity.

Conditions

Deep Brain Stimulation; Neuro: Spinal Cord Injury

Keywords

SCI; DBS; Spinal Cord Injury

Outcome Measures

Primary Outcomes (1)

• Occurence of all SAEs and AEs that are deemed related or possibly related to study procedure or to study investigational system, from implantation up to the end of the study

  Evaluate the safety of the approach in terms of tolerability of deep brain stimulation of the lateral hypothalamus in patients with chronic spinal cord injury (\> 1 year)

  Through study completion, an average of 6 months

Secondary Outcomes (3)

• Lower Extremity Motor Strength (M0-M5 score according to the AIS scale)

  Baseline ; pre-rehabilitation (2-3 weeks after surgery) ; after 1 month of rehabilitation ; after 3 months of rehabilitation

• Walking Index for Spinal Cord Injury (WISCI II)

  Baseline ; pre-rehabilitation (2-3 weeks after surgery) ; after 1 month of rehabilitation ; after 3 months of rehabilitation

• Walking speed (10MWT/6MWT)

  Baseline ; pre-rehabilitation (2-3 weeks after surgery) ; after 1 month of rehabilitation ; after 3 months of rehabilitation

Study Arms (1)

Deep brain stimulation

EXPERIMENTAL

Participants will undergo a surgery for Deep Brain Stimulation (DBS). The neurostimulation system will be used for neuro-rehabilitation of the motor function. Participants will follow a 3-month neuro-rehabilitation using DBS at a frequency of 3 times per week with physiotherapist.

Procedure: Device implantation

Interventions

Device implantation PROCEDURE

The intervention involves the insertion of lead electrodes (Medtronic SenSight Directional Lead) in the right and left lateral hypothalamus through craniotomy and an implantable pulse generator (Medtronic Model B35200 Percept™ PC) in the upper part of the pectoralis major (under the clavicle).

Deep brain stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• SCI graded as American Spinal Injury Association Impairment Scale (AIS) C or D (able to walk independently for a few meters with a walker)
• Focal spinal cord disorder caused by trauma
• Minimum 12 months post-injury
• Stable medical, physical and psychological condition as considered by Investigators
• Able to understand and interact with the study team in French or English
• Adequate care-giver support and access to appropriate medical care in patient's home community
• 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 Informed Consent prior to any study related procedures

You may not qualify if:

• Limitation of walking function based on accompanying (CNS) disorders (i.e., systemic malignant disorders, cardiovascular disorders restricting physical training, peripheral nerve disorders)
• History of significant autonomic dysreflexia
• Cognitive/brain damage
• Epilepsy
• Use of an intrathecal baclofen pump
• Any active implanted cardiac device such as pacemaker or defibrillator
• Any indication that would require diathermy
• Increased risk for defibrillation
• Severe joint contractures disabling or restricting lower limb movements
• Hematological disorders with increased risk for surgical interventions
• Congenital or acquired lower limb abnormalities (affection of joints and bone)
• Women who are pregnant (pregnancy test obligatory for woman of childbearing potential) or breastfeeding
• Lack of safe contraception for women of childbearing capacity
• Spinal cord lesion due to either a neurodegenerative disease or a tumor
• Gastrointestinal ulcers in the last five years

Sponsors & Collaborators

• Jocelyne Bloch: lead
• Ecole Polytechnique Fédérale de Lausanne: collaborator

Study Sites (1)

CHUV

Lausanne, Canton of Vaud, 1011, Switzerland

RECRUITING

Related Publications (10)

• Angeli CA, Boakye M, Morton RA, Vogt J, Benton K, Chen Y, Ferreira CK, Harkema SJ. Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury. N Engl J Med. 2018 Sep 27;379(13):1244-1250. doi: 10.1056/NEJMoa1803588. Epub 2018 Sep 24.

  PMID: 30247091 BACKGROUND

• Gill ML, Grahn PJ, Calvert JS, Linde MB, Lavrov IA, Strommen JA, Beck LA, Sayenko DG, Van Straaten MG, Drubach DI, Veith DD, Thoreson AR, Lopez C, Gerasimenko YP, Edgerton VR, Lee KH, Zhao KD. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat Med. 2018 Nov;24(11):1677-1682. doi: 10.1038/s41591-018-0175-7. Epub 2018 Sep 24.

  PMID: 30250140 BACKGROUND

• 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.

  PMID: 30382197 BACKGROUND

• Hou JM, Sun TS, Xiang ZM, Zhang JZ, Zhang ZC, Zhao M, Zhong JF, Liu J, Zhang H, Liu HL, Yan RB, Li HT. Alterations of resting-state regional and network-level neural function after acute spinal cord injury. Neuroscience. 2014 Sep 26;277:446-54. doi: 10.1016/j.neuroscience.2014.07.045. Epub 2014 Jul 30.

  PMID: 25086312 BACKGROUND

• Cortes M, Medeiros AH, Gandhi A, Lee P, Krebs HI, Thickbroom G, Edwards D. Improved grasp function with transcranial direct current stimulation in chronic spinal cord injury. NeuroRehabilitation. 2017;41(1):51-59. doi: 10.3233/NRE-171456.

  PMID: 28505987 BACKGROUND

• Kumru H, Benito-Penalva J, Valls-Sole J, Murillo N, Tormos JM, Flores C, Vidal J. Placebo-controlled study of rTMS combined with Lokomat(R) gait training for treatment in subjects with motor incomplete spinal cord injury. Exp Brain Res. 2016 Dec;234(12):3447-3455. doi: 10.1007/s00221-016-4739-9. Epub 2016 Jul 28.

  PMID: 27469242 BACKGROUND

• Kim LH, Sharma S, Sharples SA, Mayr KA, Kwok CHT, Whelan PJ. Integration of Descending Command Systems for the Generation of Context-Specific Locomotor Behaviors. Front Neurosci. 2017 Oct 18;11:581. doi: 10.3389/fnins.2017.00581. eCollection 2017.

  PMID: 29093660 BACKGROUND

• 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.

  PMID: 22654062 BACKGROUND

• Sinnamon HM. Locomotor stepping elicited by electrical stimulation of the hypothalamus persists after lesion of descending fibers of passage. Physiol Behav. 1990 Aug;48(2):261-6. doi: 10.1016/0031-9384(90)90310-z.

  PMID: 2255729 BACKGROUND

• Sinnamon HM. Preoptic and hypothalamic neurons and the initiation of locomotion in the anesthetized rat. Prog Neurobiol. 1993 Sep;41(3):323-44. doi: 10.1016/0301-0082(93)90003-b.

  PMID: 8105509 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Jocelyne Bloch, MD

  CHUV

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jocelyne Bloch, MD

CONTACT

41795562951; jocelyne.bloch@chuv.ch

Léa Bole-Feysot, MSc

CONTACT

lea.bole-feysot@chuv.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Neurosurgeon

Model Details: Single site, interventional, non-randomized

Study Record Dates

• First Submitted: May 31, 2021
• First Posted: July 16, 2021
• Study Start: June 14, 2021
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: September 6, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)