Clinical trial NCT06384170: Closed Loop Spinal Cord Stimulation for Neuromodulation of Upper Motor Neuron Lesion Spasticity
Official title: Closed Loop Spinal Cord Stimulation (SCS) for Neuromodulation of UMN-Lesion Spasticity
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Pain
Spasticity as Sequela of Stroke
Upper Motor Neuron Lesion
Keywords: Spinal Cord Stimulation
Neuromodulation
Closed-loop SCS
Post-Stroke Pain
Spasticity
Chronic Pain
Functional Recovery
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2024-04-25
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A subject who meets all of the inclusion criteria, and none of the exclusion criteria, is eligible to participate in the study. A subject is considered enrolled when the subject signs the subject informed consent form.

Brief summary: Spasticity is characterized by increased muscle tension and is a classic consequence of upper motor neuron (UMN) damage in the central nervous system, such as from stroke or trauma. Clinically, it presents as muscle resistance to passive stretching, along with clasp-knife rigidity, clonus, increased tendon reflexes, and muscle spasms. An imbalance of the descending inhibitory and muscle stretch reflexes is thought to be the cause of spasticity. Post-stroke spasticity is a common condition that occurs in 37.5-45% of cases in the acute stage and 19-57.4% in the subacute stage after a stroke. At 6 months post-stroke, spasticity develops in 42.6-49.5% of cases, and at one year, it affects 35-57.4% of individuals. In patients with cerebral palsy (CP), incidence is almost 80% while in those living with spinal cord injury the number approaches up to 93%. Traumatic brain injury (TBI) patients have a higher prevalence on initial admission to neurorehabilitation but one in three patients will have chronic spasticity. However, the Defense and Veterans Brain Injury Center report a rate of TBIs amongst deployed veterans to be around 11-23% mostly from blast and explosive trauma.

There have been studies as early as the 1980s exploring the efficacy of SCS for spasticity control, however, the credibility of many of these studies is constrained due to an incomplete comprehension of spasticity's underlying mechanisms, outdated research methods, and early limitations in implantable device technology. Intrathecal pumps for baclofen have remained as the mainstay for refractory spasticity, however, it comes with associated risks such as chemical dependence leading to acute baclofen withdrawal and requiring frequent refill requirement. Most importantly, it does not yield functional improvement of muscle activity, just suppression of spasticity. Botox is also routinely used but due to heterogeneity in muscle involvement as well as variability in provider skill, results may be inconsistent and short-lasting, requiring frequent clinic visits for repeat injections to the affected muscle groups. SCS may be able to address that gap in spasticity management.


Eligibility criteria: Inclusion Criteria:

1. First-ever stroke
2. Aged 18 and older
3. Neuropathic pain \>3 months (chronic)
4. Brain injury associated with spasticity in one or multiple limbs \>3 months post-stroke
5. No previous history of neuropathic pain or spasticity in affected limbs
6. Cognitively capable to operate the SCS system

Exclusion Criteria:

1. Inadequate Pain Severity: Patients with mild or non-debilitating pain may be excluded if the treatment is intended for individuals with moderate to severe pain.
2. Previous SCS Implantation: Patients who have previously undergone SCS implantation may be excluded to focus on those who are new to the therapy.
3. Inadequate Pain Duration: Some trials may exclude patients whose pain has not persisted for a minimum period to ensure that the pain condition is chronic.
4. Medical Comorbidities: Patients with certain medical conditions or comorbidities that may increase the risks associated with SCS, such as uncontrolled cardiovascular disease, uncontrolled diabetes, or active infections, may be excluded.
5. Psychological Factors: Patients with severe psychiatric disorders or psychological conditions that may interfere with the assessment of pain or the ability to provide informed consent may be excluded.
6. Allergies or Sensitivities: Patients with allergies to materials used in SCS devices or contraindications to the anesthesia used during implantation may be excluded.
7. Substance Abuse: Patients with active substance abuse or addiction issues may be excluded due to concerns about treatment compliance and efficacy.

Primary outcomes:
measure: Pain as assessed by Visual Analog Score
timeFrame: baseline (pre-procedure), day 1 (post-procedure) day 7 (trial lead removal), day 14 (7 days post removal)
Secondary outcomes:
measure: Spasticity Reduction as assessed by the Modified Ashworth's Score
timeFrame: baseline (pre-procedure), day 1 (post-procedure) day 7 (trial lead removal), day 14 (7 days post removal)
measure: Short Form 36 Health Survey (SF-36) score
timeFrame: baseline (pre-procedure), day 1 (post-procedure) day 7 (trial lead removal), day 14 (7 days post removal)
measure: Medication Use
timeFrame: baseline (pre-procedure), day 1 (post-procedure) day 7 (trial lead removal), day 14 (7 days post removal)
measure: Health Status as assessed by the EuroQol 5 Dimension 5 Level (EQ-5D-5L)
timeFrame: baseline (pre-procedure), day 1 (post-procedure) day 7 (trial lead removal), day 14 (7 days post removal)
Other outcomes:
measure: Spinal cord neurophysiological wave morphology
timeFrame: day 1 (post-procedure), continuous data capture until day 7 (or until trial lead removal), day 14 (7 days post removal)
measure: Spinal cord neurophysiological Current (mA/mV)
timeFrame: day 1 (post-procedure), continuous data capture until day 7 (or until trial lead removal), day 14 (7 days post removal)
measure: Spinal Cord Neurophysiological Characteristic- Conduction Velocity (m/s)
timeFrame: day 1 (post-procedure), continuous data capture until day 7 (or until trial lead removal), day 14 (7 days post removal)
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Akhil Chhatre, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mayorova L, Radutnaya M, Varyukhina M, Vorobyev A, Zhdanov V, Petrova M, Grechko A. Immediate Effects of Anti-Spastic Epidural Cervical Spinal Cord Stimulation on Functional Connectivity of the Central Motor System in Patients with Stroke- and Traumatic Brain Injury-Induced Spasticity: A Pilot Resting-State Functional Magnetic Resonance Imaging Study. Biomedicines. 2023 Aug 14;11(8):2266. doi: 10.3390/biomedicines11082266.
citation: Powell MP, Verma N, Sorensen E, Carranza E, Boos A, Fields DP, Roy S, Ensel S, Barra B, Balzer J, Goldsmith J, Friedlander RM, Wittenberg GF, Fisher LE, Krakauer JW, Gerszten PC, Pirondini E, Weber DJ, Capogrosso M. Epidural stimulation of the cervical spinal cord for post-stroke upper-limb paresis. Nat Med. 2023 Mar;29(3):689-699. doi: 10.1038/s41591-022-02202-6. Epub 2023 Feb 20.