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 : May 26, 2020
|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|
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 endpoint will be improvement of locomotion as determined by the 6-Minute walking test.
Secondary endpoints will be electrophysiological/clinical 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 6 months 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. 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 e.g. 50Hz will be applied to determine activation of lower limb muscle activity with electroneuromyographic recordings and detection of possible amelioration of intended active movements. 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. 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 surgeon will decide, if the impulse generator will be implanted in the same surgery or delayed. Subjects will undergo regular assessments until discharge and further on in an outpatient setup around day 30 post-surgery, as well as 3 and 6 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 Multicenter 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 2022|
|Estimated Study Completion Date :||December 2022|
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 Medtronic 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 10 Meter Walking Test towards baseline [ Time Frame: preoperative, early postop, before discharge, 1,3,6 months follow-up ]Standardized test. Patient is asked to walk 10 meters as quickly as possible. Result is the speed (m/s)
- Change in Timed Up and Go test (TUG) towards baseline [ Time Frame: preoperative, early postop, before discharge, 1,3,6 months follow-up ]Standardized test. Patient is asked to stand up from a sitting into Standing Position and walk 3 m and return to seated position. Result ist time.
- Kinematic assessment during overground and treadmill walking [ Time Frame: preoperative, early postop, before discharge, 1,3,6 months follow-up ]Individuals are secured using the FLOAT.
- Change in Spinal cord Independence measure (SCIM III) towards baseline [ Time Frame: preoperative, early postop, before discharge, 1,3,6 months follow-up ]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, early postop, before discharge, 1,3,6 months follow-up ]Standardized tool measuring the subject's ability to walk. Result is score.
- Long-term monitoring of physical activity [ Time Frame: Continuously between discharge and 6 months follow-up ]Wearable and wireless sensors are mounted to the patient and wheelchair for constant monitoring of physical activity
- Electrophysiology [ Time Frame: Baseline and several time-points throughout the study. ]SSEPs, MEPs, DBS-EPs, LFPs, EMG
- Changes in Electroencephalography towards baseline [ Time Frame: preoperative, intraoperative, early postop, 6 months follow-up ]Evaluation for the occuracne of EEG abnormalities
- Change in Quality of life towards baseline [ Time Frame: preoperative, 1,3,6 months follow-up ]Standardized QOL tool (SF-36). Result is score.
- Change in lower urinary tract function towards baseline [ Time Frame: preoperative, 6 months follow-up ]Standardized tools QUALIVEEN, bladder diary, urodynamic assessments, renal and bladder ultrasound.
- Change in sexual functions towards baseline [ Time Frame: preoperative, 1,3,6 months follow-up ]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, early postop, before discharge, 1,3,6 months follow-up ]Use of the standardized tool MAS (Modified Ashword Scale). Result is score.
- Changes in ASIA impairment scale (AIS) [ Time Frame: preoperative, early postop, before discharge, 1,3,6 months follow-up ]Assment of neurological status of individual with SCI
- Change in Upper limb Sensation, Strength and Prehension towards baseline [ Time Frame: preoperative, 6 months follow-up ]Standardized tool GRASSP
- Change in sleepiness towards baseline [ Time Frame: preoperative, 1,3,6 months follow-up ]Standardized tool Epworth Sleepiness Scale
- Change in Fatigue towards baseline [ Time Frame: preoperative, 1,3,6 months follow-up ]Standardized tool Fatigue Severity Scale
- Change in pain sensation towards baseline [ Time Frame: preoperative, 1,3,6 months follow-up ]Standardized tools EPAF and SCIPI
- Change in 6 Minute Walk Test at other timepoints towards baseline [ Time Frame: Screening, early postop, before discharge, 1,3 months follow-up ]Standardized test. Patient is asked to walk for 6 minutes. Result is the distance
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: Iris Krüsi||+4144386 ext 1111||DBS-SCI@balgrist.ch|
|Balgrist University Hospital||Recruiting|
|Zurich, Switzerland, 8008|
|Contact: Iris Krüsi +4144386 ext 1111 DBS-SCI@balgrist.ch|
|Principal Investigator: Armin Curt, MD|
|Principal Investigator:||Lennart H Stieglitz, MD||University Hospital Zurich, Neurosurgery|