Clinical trial NCT04965727: Deep Brain Stimulation of the Lateral Hypothalamus to Augment Motor Function of Patients With Spinal Cord Injury
Official title: Deep Brain Stimulation of the Lateral Hypothalamus to Augment Motor Function of Patients With Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Deep Brain Stimulation
Neuro: Spinal Cord Injury
Keywords: SCI
DBS
Spinal Cord Injury
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
Collaborators: name: Ecole Polytechnique Fédérale de Lausanne
First posted: 2021-07-16
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single site, interventional, non-randomized
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate safety of Deep Brain Stimulation (DBS) of the lateral hypothalamus (LH) and whether the use of DBS can increase motor performance in patients with chronic spinal cord injury (SCI). The hypothesis, based on preclinical findings, is that DBS of the lateral hypothalamus can acutely augment leg motor function after SCI, and that the use of lateral hypothalamus DBS can be an adjunct during rehabilitation to promote recovery and long-term neuroplasticity.

Detailed description: The investigators hypothesize that deep brain stimulation (DBS) delivered in the lateral hypothalamus (LH) can augment leg motor function in humans with SCI. DBS is a well-established neurosurgical technique that is used routinely in humans. For example, DBS is commonly used to regulate the activity of basal ganglia circuits in order to treat movement disorders like Parkinson's disease or tremor. For the past decade, the hypothalamus has been safely targeted to treat diseases such as obesity and cluster headache.

In this study, The investigators propose to test the safety and preliminary efficacy of Lateral Hypothalamus DBS in 3 individuals with incomplete SCI, as a potential basis for larger clinical trials. The investigators anticipate that such clinical trials will evaluate the respective impact of, and potential synergy between, DBS of the lateral hypothalamus and epidural electrical stimulation of the lumbar spinal cord to augment recovery from SCI.

The study intervention consists of 7 phases preceded by pre-screening:

* Screening and enrolment
* Baseline - Pre-implantation
* Surgery
* Calibration
* Pre-rehabilitation
* Rehabilitation
* Post-rehabilitation
* (Optional and conditional): safety follow-up period

Measures will be performed before surgical intervention, after surgery but before training (Pre-rehabilitation), at regular intervals during training and at the end of the training phase (post-rehabilitation).

The study will take place at the CHUV (Lausanne, Switzerland). A total of 3 participants will be enrolled in the study and implanted with the Medtronic Percept PC and 2 Medtronic SenSight DIrectional lead (left and right LH). All participants will undergo the same treatment and procedures. The active duration of the study will be approximately 7 to 8 months.

If deemed safe and beneficial by the Principal Investigator, participants may keep using the investigational device independently for 3 more years by entering the safety follow-up period at the end of the main study phase.

Eligibility criteria: Inclusion Criteria:

* SCI graded as American Spinal Injury Association Impairment Scale (AIS) C or D (able to walk independently for a few meters with a walker)
* Focal spinal cord disorder caused by trauma
* Minimum 12 months post-injury
* Stable medical, physical and psychological condition as considered by Investigators
* Able to understand and interact with the study team in French or English
* Adequate care-giver support and access to appropriate medical care in patient's home community
* Must agree to comply in good faith with all conditions of the study and to attend all required study training and visit
* Must provide and sign Informed Consent prior to any study related procedures

Exclusion Criteria:

* Limitation of walking function based on accompanying (CNS) disorders (i.e., systemic malignant disorders, cardiovascular disorders restricting physical training, peripheral nerve disorders)
* History of significant autonomic dysreflexia
* Cognitive/brain damage
* Epilepsy
* Use of an intrathecal baclofen pump
* Any active implanted cardiac device such as pacemaker or defibrillator
* Any indication that would require diathermy
* Increased risk for defibrillation
* Severe joint contractures disabling or restricting lower limb movements
* Hematological disorders with increased risk for surgical interventions
* Congenital or acquired lower limb abnormalities (affection of joints and bone)
* Women who are pregnant (pregnancy test obligatory for woman of childbearing potential) or breastfeeding
* Lack of safe contraception for women of childbearing capacity
* Spinal cord lesion due to either a neurodegenerative disease or a tumor
* Gastrointestinal ulcers in the last five years
* Known or suspected eye disorders or diseases
* Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.)
* Any other anatomic or co-morbid conditions that, in the Investigator's opinion, could limit the patient's ability to participate in the study or to comply with follow-up requirements, or impact the scientific soundness of the study results
* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
* Participation in another study with investigational drug within the 30 days preceding and during the present study
* Enrolment of the investigator, his/her family members, employees and other dependent persons
* Participation in another locomotor training study
* Refusal to be informed of any finding during the study

Primary outcomes:
measure: Occurence of all SAEs and AEs that are deemed related or possibly related to study procedure or to study investigational system, from implantation up to the end of the study
timeFrame: Through study completion, an average of 6 months
Secondary outcomes:
measure: Lower Extremity Motor Strength (M0-M5 score according to the AIS scale)
timeFrame: Baseline ; pre-rehabilitation (2-3 weeks after surgery) ; after 1 month of rehabilitation ; after 3 months of rehabilitation
measure: Walking Index for Spinal Cord Injury (WISCI II)
timeFrame: Baseline ; pre-rehabilitation (2-3 weeks after surgery) ; after 1 month of rehabilitation ; after 3 months of rehabilitation
measure: Walking speed (10MWT/6MWT)
timeFrame: Baseline ; pre-rehabilitation (2-3 weeks after surgery) ; after 1 month of rehabilitation ; after 3 months of rehabilitation
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: CHUV
state: Vaud
Study officials:
affiliation: CHUV
name: Jocelyne Bloch, MD
role: PRINCIPAL_INVESTIGATOR
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