Closed Loop Spinal Cord Stimulation for Neuromodulation of Upper Motor Neuron Lesion Spasticity

Chronic Pain Clinical Trial

— CLONUS  

Official title:

Closed Loop Spinal Cord Stimulation (SCS) for Neuromodulation of UMN-Lesion Spasticity

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06384170
• Other study ID #: IRB00442113
• Status: Not yet recruiting
• Start date: July 2024
• Est. completion date: May 2026

Study information

• Verified date: April 2024
• Source: Johns Hopkins University
• Contact: Harman Chopra, MD
• Phone: 7188108752
• Email: harmanchopra322[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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of many of these studies is constrained due to an incomplete comprehension of spasticity's underlying mechanisms, outdated research methods, and early limitations in implantable device technology.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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: May 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Pain
• Muscle Spasticity
• Spasticity as Sequela of Stroke

Intervention

Device:
• Spinal Cord Stimulation- Closed loop
This is a percutaneously placed epidural electrode that is connected to a battery-powered impulse generator for power. The electrical delivery is monitored in real-time with the measurement of evoked compound action potentials and adjusted to provide titration of therapeutic stimulation delivery.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Saluda Medical Pty Ltd

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Spinal cord neurophysiological wave morphology	Assessed using data downloaded from the implanted closed-loop SCS system. Will measure and report on the various morphologies of the Evoked Compound Action Potentials (ECAPs).	day 1 (post-procedure), continuous data capture until day 7 (or until trial lead removal), day 14 (7 days post removal)
Other	Spinal cord neurophysiological Current (mA/mV)	Assessed using data downloaded from the implanted closed-loop SCS system. Will measure and report on the current (mA/mV) of the Evoked Compound Action Potentials (ECAPs).	day 1 (post-procedure), continuous data capture until day 7 (or until trial lead removal), day 14 (7 days post removal)
Other	Spinal Cord Neurophysiological Characteristic- Conduction Velocity (m/s)	Assessed using data downloaded from the implanted closed-loop SCS system. Will measure and report on the conduction velocity (m/s) of the Evoked Compound Action Potentials (ECAPs).	day 1 (post-procedure), continuous data capture until day 7 (or until trial lead removal), day 14 (7 days post removal)
Primary	Pain as assessed by Visual Analog Score	Visual Analog Scores, pain score with possible range from zero (no pain) to ten (worst imaginable pain)	baseline (pre-procedure), day 1 (post-procedure) day 7 (trial lead removal), day 14 (7 days post removal)
Secondary	Spasticity Reduction as assessed by the Modified Ashworth's Score	Modified Ashworth's Scores range from 0-4. Minimum score is '0' meaning no increase in tone. Maximum score is '4' meaning limb is ridged in flexion and extension. The lower the score the better the outcome	baseline (pre-procedure), day 1 (post-procedure) day 7 (trial lead removal), day 14 (7 days post removal)
Secondary	Short Form 36 Health Survey (SF-36) score	The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. The total score on the SF-36 ranges from 0 - 100 Lower scores = more disability, higher scores = less disability	baseline (pre-procedure), day 1 (post-procedure) day 7 (trial lead removal), day 14 (7 days post removal)
Secondary	Medication Use	Dose and frequency of medication use for current symptoms	baseline (pre-procedure), day 1 (post-procedure) day 7 (trial lead removal), day 14 (7 days post removal)
Secondary	Health Status as assessed by the EuroQol 5 Dimension 5 Level (EQ-5D-5L)	Effects on health-related quality of life that comprises five dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. The survey is scored in two separate sections. The first section is measured by a minimum score of 5 and a maximum score of 25. Higher score greater level of problems. The second section measures self report health status on a 0 to 100. Higher score best health.	baseline (pre-procedure), day 1 (post-procedure) day 7 (trial lead removal), day 14 (7 days post removal)