Deep Brain Stimulation in Patients With Incomplete Spinal Cord Injury for Improvement of Gait (DBS-SCI)
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|ClinicalTrials.gov Identifier: NCT03053791|
Recruitment Status : Recruiting
First Posted : February 15, 2017
Last Update Posted : October 19, 2018
|Condition or disease||Intervention/treatment||Phase|
|Spinal Cord Injury||Procedure: Deep brain stimulation in mesencephalic locomotor region Device: Implantation of a Deep brain stimulation system||Not Applicable|
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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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single group of patients with spinal cord injury and spared fibers.|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||February 1, 2017|
|Estimated Primary Completion Date :||April 2020|
|Estimated Study Completion Date :||December 2020|
Experimental: Intervention group
Single-armed study. All patients will receive treatment.
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.
- 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
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03053791
|Contact: Lennart H Stieglitz, MD||+4144255 ext 9905||Lennart.Stieglitz@usz.ch|
|Contact: Andrea Prusse||+4144386 ext 1111||DBS-SCI@balgrist.ch|
|Balgrist University Hospital||Recruiting|
|Zurich, Switzerland, 8008|
|Contact: Andrea Prusse +4144386 ext 1111 DBS-SCI@balgrist.ch|
|Principal Investigator: Armin Curt, MD|
|Principal Investigator:||Lennart H Stieglitz, MD||University Hospital Zurich, Neurosurgery|