We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Deep Brain Stimulation in Patients With Incomplete Spinal Cord Injury for Improvement of Gait (DBS-SCI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03053791
Recruitment Status : Recruiting
First Posted : February 15, 2017
Last Update Posted : February 15, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

April 26, 2016
February 15, 2017
February 15, 2017
February 1, 2017
April 2019   (Final data collection date for primary outcome measure)
Change in 6 Minute Walk Test at baseline and 6 months post intervention [ Time Frame: preoperative, 6 months post intervention ]
Standardized test. Patient is asked to walk for 6 minutes. Result is the distance covered
Same as current
No Changes Posted
  • Change in Timed Up and Go test (TUG) towards baseline [ Time Frame: preoperative, 4-9 days postop, 14 days postop, 1,3,6 months postop ]
    Standardized test. Patient is asked to stand up from a sitting into Standing Position and walk 3 m. Result ist time.
  • Change in 6 Minute Walk Test towards baseline [ Time Frame: preoperative, 4-9 days postop, 14 days postop, 1,3 months postop ]
    Standardized test. Patient is asked to walk for 6 minutes. Result is the distance
  • Change in Spinal cord Independence measure (SCIM III) towards baseline [ Time Frame: preoperative, 4-9 days postop, 14 days postop, 1,3,6 months postop ]
    Standardized tool measuring the degree of independence of the subject. Result is score.
  • Change in Walking index for spinal cord injury (WISCI II) towards baseline [ Time Frame: preoperative, 4-9 days postop, 14 days postop, 1,3,6 months postop ]
    Standardized tool measuring the subject's ability to walk. Result is score.
  • Change in Quality of life towards baseline [ Time Frame: preoperative, 1,3,6 months postop ]
    Standardized QOL tool (SF-36). Result is score.
  • Change in bladder function towards baseline [ Time Frame: preoperative, 6 months postop ]
    Standardized tool QUALIVEEN. Result is score.
  • Change in bladder function towards baseline [ Time Frame: preoperative, 6 months postop ]
    Bladder diary. Drink Portion (result is mL)
  • Change in bladder function towards baseline [ Time Frame: preoperative, 6 months postop ]
    Bladder diary. Urine Portion (result is mL)
  • Change in bladder function towards baseline [ Time Frame: preoperative, 6 months postop ]
    Bladder diary. Urge (result is score 0-4)
  • Change in bladder function towards baseline [ Time Frame: preoperative, 6 months postop ]
    Bladder diary. Unwanted loss of Urine (result is semi-quantitative no/Little/some/a lot)
  • Change in bladder function towards baseline [ Time Frame: preoperative, 6 months postop ]
    Bladder diary. Change of diapers (yes/no)
  • Change in bladder function towards baseline [ Time Frame: preoperative, 6 months postop ]
    Bladder diary. Quality of diapers (semi-quantitative dry/moist/wet)
  • Change in bladder function towards baseline [ Time Frame: preoperative, 6 months postop ]
    Bladder diary. pain (semi-quantitative 0-10)
  • Change in sexual functions towards baseline [ Time Frame: preoperative, 6 months postop ]
    Use of the standardized tools FSFI (Female Sexual Function Index), result is score respectively IIEF (International Index of Erectile Function), result is score
  • Change in spasticity towards baseline [ Time Frame: preoperative, 4-9 days postop, 14 days postop, 1,3,6 months postop ]
    Use of the standardized tool MAS (Modified Ashword Scale). Result is score.
Same as current
Not Provided
Not Provided
 
Deep Brain Stimulation in Patients With Incomplete Spinal Cord Injury for Improvement of Gait
A Phase I/II Open-label Single Center Trial to Evaluate Safety and Preliminary Efficacy of Unilateral Deep Brain Stimulation of the Mesencephalic Locomotor Region in Patients With Incomplete Spinal Cord Injury
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.

After approval by the local ethics committee we will perform a phase I open-label trial to evaluate safety and preliminary efficacy of unilateral deep brain stimulation of the mesencephalic locomotor region in patients with incomplete spinal cord injury. Male or female subjects (18-75 year-old) with completed in-patient rehabilitation will be enrolled for screening evaluations at minimum 5 months post-injury. DBS operation will be performed at minimum 6 months post-injury. Primary endpoints will be improvement of posture or locomotion as determined by functional tests validated in spinal cord injury trials, such as the 6 Minute Walk Test, Timed Up and Go Test, Spinal cord independence Measure (SCIM III), Walking Index for Spinal Cord Injury (WISCI II).

Secondary endpoints will be electrophysiological and image based characterization of the mesencephalic locomotor region, questionnaire based/ professional assessments of quality of life, pain, micturition, sleep behavior, cognitive function and psychiatric evaluations (mood, anxiety, impulse control, delusional and affective disorders). The study population will consist of 5 subjects and the study period for each patient is 1 year postoperatively. Briefly, candidate subjects, able to stand with a walker or 2 crutches and with stable neurological condition will have to meet all of the inclusion and none of the exclusion criteria. Subjects will have preoperative examinations (e.g. MRI scans of the head and spine, neuropsychological, psychiatric and sleep status etc.) according to our standard protocols of DBS for movement disorders, especially Parkinson's disease, based on certification criteria of Highly-Specialized-Medicine DBS centers in Switzerland. Furthermore, an investigational preoperative 7 Tesla MRI is part of the protocol for more precise depiction of brainstem anatomy. Neurological assessments for spinal cord injury impairment as defined by study protocol will be performed at the University Hospital Balgrist.

The operation will be performed in the Division of Neurosurgeon by the neurosurgical PI of this study: awake subjects will have their heads fixed in a stereotactic ring with local anesthesia and high resolution head scans will be performed to define the stereotactic space for targeting through anatomical landmarks defined on individual MRI as described in the literature. In contrast to bilateral implantations in Parkinsonian patients, here, a single burr hole will be opened under local anesthesia on the contralateral side of the worse lower extremity of the subject. Microelectrode recordings of single-cells as well as local field potentials will be mapped starting 1 cm prior the MLR target. Four states will be analysed: resting state, imagination of walking, passive and active lower limb movement. These recordings will help to further determine the places of stimulation as the next step of surgery. Here, slow increases of the stimulation amplitude with a constant frequency of 50Hz will be applied to determine activation of lower limb muscle activity with electroneuromyographic recordings and detection of possible amelioration of intended active movements with a bedside lower limb trainer. Since the subject is awake, possible side effects will be professionally monitored at each site of stimulation and amplitude. Next, the electrode for recording and stimulation will be exchanged with the standard quadripolar DBS electrode for Parkinson's disease patients (1.27 mm in diameter, 1.5mm length of each contact and 0.5 mm spacing in between) using fluoroscopy. It will be fixed to the skull and externalized distally by temporary extensions through a subgaleal tunneling to be finally sutured at the skin. All subjects will receive an intraoperative head scan to verify correct placement and accuracy. If refinement is not necessary, the first operative procedure will be regarded as finished and the subject will be transferred to the intermediate care unit overnight to recover from surgery. The subject will be mobilized during day 1 to 3 and sleep laboratory recordings will be performed. Meanwhile stimulation settings will be tested in a close interdisciplinary approach between the PI and the neurological team to determine the best parameters in balancing effects and possible side effects. Neurological assessments at the University Hospital Balgrist are going to take place between day 4 to 9. In case of improvement of posture or gait second surgery will take place around 10th postoperative day in general anesthesia with placement of internal extension cables that connect the electrodes to a single channel pulse generator. Otherwise, the electrode will be removed. Subjects with fully implanted DBS will undergo regular assessments on day 14 (discharge) and further on in an outpatient setup around day 30 post-surgery, as well as 3, 6 and 12 months afterwards. Rehabilitative postoperative treatment will be assisted by using the recently CE certificated and award winning FLOAT system ("Free Levitation for Overground Active Training") which allows robotic multidirectional relief of body weight and exact gait/posture analysis.

Interventional
Not Provided
Intervention Model: Single Group Assignment
Intervention Model Description:
Single group of patients with spinal cord injury and spared fibers.
Masking: None (Open Label)
Primary Purpose: Treatment
Spinal Cord Injury
  • Procedure: Deep brain stimulation in mesencephalic locomotor region
    Implantation of Electrodes in the Mesencephalic Locomotor Region for improvement of Locomotion and Gait
  • Device: Implantation of a Deep brain stimulation system
    Implantation of a Medtrinic Activa SC Impulse Generator for chronic Stimulation of the selected target.
Experimental: Intervention group
Single-armed study. All patients will receive treatment.
Interventions:
  • Procedure: Deep brain stimulation in mesencephalic locomotor region
  • Device: Implantation of a Deep brain stimulation system
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
5
December 2019
April 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Informed Consent as documented by signature
  2. Must participate in two assessment sessions before enrollment
  3. Willingness and ability to comply with the protocol
  4. Male or female subjects
  5. Age 18-75
  6. Motor incomplete SCI
  7. Level of lesion: T10 and above, based on AISA level, preservation of sacral function
  8. Focal spinal cord disorder caused by either trauma or non-traumatic and non-progressive condition
  9. Minimum 6 months after original incident
  10. Completed in-patient rehabilitation program
  11. WISCI II, level >2 (0-20 items): assistance of one or more persons. Ability to walk at least 10 meters
  12. SCIM-III Mobility sub score >2 on the Mobility Indoors, Mobility for Moderate Distances
  13. Stable medical and physical condition.
  14. Adequate care-giver support

Exclusion Criteria:

  1. Enrollment of the investigator, his/her family members, employees
  2. Limitation of standing and walking function based on accompanying (CNS) disorders
  3. Cardiovascular disorders
  4. Autonomic dysreflexia
  5. Cognitive/brain damage
  6. Drug refractory Epilepsy
  7. Severe joint contractures disabling or restricting lower limb movements
  8. Haematological disorders
  9. Participation in another study with investigational drug within the 30 days preceding and during the present study
  10. Congenital or acquired lower limb abnormalities
  11. Women who are pregnant or breast feeding or planning a pregnancy during the course of the study
  12. Lack of safe contraception
  13. Inability to follow the procedures of the study
  14. Known or suspected non-compliance, drug or alcohol abuse
  15. Current or prior malignancy
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: Lennart H Stieglitz, MD +4144255 ext 9905 Lennart.Stieglitz@usz.ch
Contact: Andrea Prusse +4144386 ext 1111 DBS-SCI@balgrist.ch
Switzerland
 
 
NCT03053791
SNCTP000000598
Yes
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
University of Zurich
University of Zurich
Balgrist University Hospital
Principal Investigator: Lennart H Stieglitz, MD University Hospital Zurich, Neurosurgery
University of Zurich
February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP