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

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

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of many of these studies is constrained due to an incomplete comprehension of spasticity's underlying mechanisms, outdated research methods, and early limitations in implantable device technology.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

Study Overview

• Status: Withdrawn
• Conditions: Chronic Pain; Spasticity as Sequela of Stroke; Upper Motor Neuron Lesion
• Intervention / Treatment: Device: Spinal Cord Stimulation- Closed loop

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Interventional; Patients identified with post-stroke pain due to spasticity. Patients will be evaluated for spinal cord stimulation trial. The trial will be for 7 days.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Saluda Medical Pty Ltd
• Investigators: Principal Investigator: Akhil Chhatre, MD, Johns Hopkins University

Publications and helpful links

General Publications

• 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.
• 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.
• Abstracts of Scientific Papers and Posters Presented at Physiatry '25: February 25 - March 1, 2025. Am J Phys Med Rehabil. 2025 Jun 1;104(6S Suppl 1):S1-S240. doi: 10.1097/PHM.0000000000002746. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: April 22, 2024
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 25, 2024

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Neuromodulation; Chronic Pain; Spinal Cord Stimulation; Spasticity; Functional Recovery; Closed-loop SCS; Post-Stroke Pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Muscle Spasticity; Chronic Pain
• Other Study ID Numbers: IRB00442113

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No