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Trial record 2 of 28 for:    Recruiting, Not yet recruiting Studies | Spinal Cord Injuries | Switzerland

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
Sponsor:
Collaborators:
Balgrist University Hospital
ETH Zurich
Information provided by (Responsible Party):
University of Zurich

Tracking Information
First Submitted Date  ICMJE April 26, 2016
First Posted Date  ICMJE February 15, 2017
Last Update Posted Date May 26, 2020
Actual Study Start Date  ICMJE February 1, 2017
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2017)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2020)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2017)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Deep Brain Stimulation in Patients With Incomplete Spinal Cord Injury for Improvement of Gait
Official Title  ICMJE 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
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.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
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
Condition  ICMJE Spinal Cord Injury
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 10, 2017)
5
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date April 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Informed Consent
  2. Participation in two assessment sessions before enrollment (Screening and baseline)
  3. Willingness and ability to comply with the protocol and to attend required study training and visits
  4. Male or female subjects
  5. Age 18-75
  6. Motor incomplete SCI
  7. Level of lesion: T10 and above, based on AIS level, preservation of sacral function
  8. Focal spinal cord disorder caused by either trauma or non-traumatic and non-progressive condition (like hemorrhage, benign tumor)
  9. Minimum 6 months of recovery after SCI
  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. Stable medical and physical condition.
  13. Adequate care-giver support and access to appropriate medical care in patient's home community

Exclusion Criteria:

  1. Enrollment of the investigator, his/her family members, employees and other dependent persons
  2. Limitation of standing and walking function based on accompanying (CNS) disorders
  3. Cardiovascular disorders restricting physical training or peripheral nerve disorders
  4. Implanted technical devices (pacemaker, defibrillator)
  5. History of significant autonomic dysreflexia
  6. Cognitive disorders/brain damage
  7. Drug refractory epilepsy
  8. Severe joint contractures disabling or restricting lower limb movements
  9. Haematological disorders with increased risk of bleeding during surgical interventions
  10. Participation in another study with investigational drug within the 30 days preceding and during the present study
  11. Congenital or acquired lower limb abnormalities (affection of joints and bone)
  12. Women who are pregnant or breast feeding or planning a pregnancy during the course of the study
  13. Lack of safe contraception
  14. Inability of the participant to follow the procedures of the study, e.g. due to language problems, psychological problems, dementia etc.
  15. Known or suspected non-compliance, drug or alcohol abuse
  16. Current or prior malignancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lennart H Stieglitz, MD +4144255 ext 9905 Lennart.Stieglitz@usz.ch
Contact: Iris Krüsi +4144386 ext 1111 DBS-SCI@balgrist.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03053791
Other Study ID Numbers  ICMJE SNCTP000000598
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Zurich
Study Sponsor  ICMJE University of Zurich
Collaborators  ICMJE
  • Balgrist University Hospital
  • ETH Zurich
Investigators  ICMJE
Principal Investigator: Lennart H Stieglitz, MD University Hospital Zurich, Neurosurgery
PRS Account University of Zurich
Verification Date May 2020

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