Deep Brain Stimulation in Patients With Incomplete Spinal Cord Injury for Improvement of Gait

NCT03053791 | Recruiting DMC

• 1 other identifier: SNCTP000000598
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Spinal cord injuries are anatomically mostly incomplete, showing tissue bridges of the spinal cord at the injury site. Of the 60% functionally incomplete patients, about half face a life in the wheelchair. Besides conventional rehabilitation, no prominsing further treatment options exist. One of the most plastic systems involved in locomotion is the pontomedullary reticulospinal tract, which is the oldest locomotor command system existing in most vertebrates, including primates. Muscle activation patterns for limb movements are programmed in the spinal cord and have to be activated and coordinated through commands from the so called mesencephalic locomotor region (MLR). The MLR consists of nerve cells in the lower mesencephalic tegmentum sending uni- and bilateral signals through the medullary reticulospinal tracts. Classical physiological studies showed that electrical stimulation of the MLR induce locomotion. For the first time this approach was transferred and recently published in a model of induced incomplete spinal cord injury by the Schwab group. Rats severly impaired in motor hindlimb control with only 10-20% spared white matter, recovered with fully functional weight bearing locomotion under MLR deep brain stimulation (DBS). Even rats with only 2-10% spared white matter regained weight supporting stepping. DBS is a clinical standard treatment option in patients with movement disorders but does not relieve all symptoms. Therefore, small studies of MLR stimulations have been safely used in Parkinsonian patients showing freezing of gait and frequent falls with variable results. In a translational approach, we aim at performing a multidisciplinary phase one clinical trial with 5 patients and incomplete spinal cord injury. With the means of our established universitary setup for DBS treatments the operations will be performed unilaterally under local anaesthesia in the Division of Neurosurgery, USZ, with perioperative electrophysiological recordings, clinical assessments and gait analysis under test stimulation in the Spinal Cord Injury Center Balgrist.

Conditions

Spinal Cord Injury

Keywords

Deep brain stimulation; DBS; Spinal cord injury; SCI; Paraplegia; Mesencephalic locomotor region; MLR; Pedunculopontine nucleus; PPN

Outcome Measures

Primary Outcomes (1)

• Change in 6 Minute Walk Test at baseline and 6 months post intervention

  Standardized test. Patient is asked to walk for 6 minutes. Result is the distance covered

  preoperative, 6 months post intervention

Secondary Outcomes (18)

• Change in 10 Meter Walking Test towards baseline

  preoperative, early postop, before discharge, 1,3,6 months follow-up

• Change in Timed Up and Go test (TUG) towards baseline

  preoperative, early postop, before discharge, 1,3,6 months follow-up

• Kinematic assessment during overground and treadmill walking

  preoperative, early postop, before discharge, 1,3,6 months follow-up

• Change in Spinal cord Independence measure (SCIM III) towards baseline

  preoperative, early postop, before discharge, 1,3,6 months follow-up

• Change in Walking index for spinal cord injury (WISCI II) towards baseline

  preoperative, early postop, before discharge, 1,3,6 months follow-up

Study Arms (1)

Intervention group

EXPERIMENTAL

Single-armed study. All patients will receive treatment.

Procedure: Deep brain stimulation in mesencephalic locomotor region; Device: Implantation of a Deep brain stimulation system

Interventions

Deep brain stimulation in mesencephalic locomotor region PROCEDURE

Implantation of Electrodes in the Mesencephalic Locomotor Region for improvement of Locomotion and Gait

Intervention group

Implantation of a Deep brain stimulation system DEVICE

Implantation of a Medtronic Percept PC Impulse Generator for chronic Stimulation of the selected target.

Intervention group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent
• Participation in two assessment sessions before enrollment (Screening and baseline)
• Willingness and ability to comply with the protocol and to attend required study training and visits
• Male or female subjects
• Age 18-75
• Motor incomplete SCI
• Level of lesion: T10 and above, based on AIS level, preservation of sacral function
• Focal spinal cord disorder caused by either trauma or non-traumatic and non-progressive condition (like hemorrhage, benign tumor)
• Minimum 3 months of recovery after SCI, maximum 2 years after trauma
• Completed in-patient rehabilitation program
• WISCI II, level \>2 (0-20 items): assistance of one or more persons. Ability to walk at least 10 meters
• Stable medical and physical condition.
• Adequate care-giver support and access to appropriate medical care in patient's home community

You may not qualify if:

• Enrollment of the investigator, his/her family members, employees and other dependent persons
• Limitation of standing and walking function based on accompanying (CNS) disorders
• Cardiovascular disorders restricting physical training or peripheral nerve disorders
• Implanted technical devices (pacemaker, defibrillator)
• History of significant autonomic dysreflexia
• Cognitive disorders/brain damage
• Drug refractory epilepsy
• Severe joint contractures disabling or restricting lower limb movements
• Haematological disorders with increased risk of bleeding during surgical interventions
• Participation in another study with investigational drug within the 30 days preceding and during the present study
• Congenital or acquired lower limb abnormalities (affection of joints and bone)
• Women who are pregnant or breast feeding or planning a pregnancy during the course of the study
• Lack of safe contraception
• Inability of the participant to follow the procedures of the study, e.g. due to language problems, psychological problems, dementia etc.
• Known or suspected non-compliance, drug or alcohol abuse

Sponsors & Collaborators

• University of Zurich: lead
• Balgrist University Hospital: collaborator
• ETH Zurich: collaborator
• Wings for Life: collaborator

Study Sites (1)

Balgrist University Hospital

Zurich, 8008, Switzerland

RECRUITING

Related Publications (2)

• Hofer AS, Stieglitz LH, Bolliger M, Filli L, Cathomen A, Willi R, Lerch I, Krusi I, Giagiozis M, Meyer C, Schubert M, Hubli M, Kessler TM, Demko L, Baumann CR, Imbach L, Oertel MF, Prusse A, Kiseleva A, Regli L, Schwab ME, Curt A. Cuneiform Nucleus Stimulation Can Assist Gait Training to Promote Locomotor Recovery in Individuals With Incomplete Tetraplegia. Ann Neurol. 2025 Sep 10. doi: 10.1002/ana.78026. Online ahead of print.

  PMID: 40927915 DERIVED

• Stieglitz LH, Hofer AS, Bolliger M, Oertel MF, Filli L, Willi R, Cathomen A, Meyer C, Schubert M, Hubli M, Kessler TM, Baumann CR, Imbach L, Krusi I, Prusse A, Schwab ME, Regli L, Curt A. Deep brain stimulation for locomotion in incomplete human spinal cord injury (DBS-SCI): protocol of a prospective one-armed multi-centre study. BMJ Open. 2021 Sep 30;11(9):e047670. doi: 10.1136/bmjopen-2020-047670.

  PMID: 34593490 DERIVED

MeSH Terms

Conditions

Spinal Cord Injuries; Paraplegia

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Lennart H Stieglitz, MD

  University Hospital Zurich, Neurosurgery

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lennart H Stieglitz, MD

CONTACT

+4144255; Lennart.Stieglitz@usz.ch

Iris Krüsi

CONTACT

+4144386; DBS-SCI@balgrist.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

Model Details: Single group of patients with spinal cord injury and spared fibers.

Study Record Dates

• First Submitted: April 26, 2016
• First Posted: February 15, 2017
• Study Start: March 15, 2018
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)