From Nerve to Brain: Toward a Mechanistic Understanding of Spinal Cord Stimulation in Human Subjects

This is a multicenter prospective study of patients who currently have stably implanted spinal cord simulators. Patients will be randomly assigned to turn on or off their spinal cord stimulators for two week intervals up to six weeks after enrollment, and on the final day of study participation, for one hour intervals, in a multi-crossover design.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain
• Intervention / Treatment: Other: Spinal Cord Stimulator Set to Minimal/No Stimulation Setting; Other: Usual Care

Detailed Description

The fundamental hypothesis for this study is that spinal cord stimulators modulate the excitability of primary afferent neurons to reduce pain, and that these changes can be detected by measurement of axonal excitability. For the primary outcome, the study investigators will leverage the sensitivity and reproducibility of threshold tracking nerve conduction studies to detect changes in the excitability of thickly myelinated nerve fibers. The study investigators will use microneurography to record directly from primary nociceptive afferents. Finally, the study investigators will perform plasma inflammatory cytokine profiles to measure changes due to spinal cord stimulators. By correlating changes in outcome measurements with subject pain levels during therapeutic versus minimal spinal cord stimulators settings, this study will determine which effects may be mechanistically relevant and which are unrelated to reduction in pain. Thus, this study will use robust, reproducible techniques to define the peripheral, central, and systemic effects of spinal cord stimulators.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Brian Wainger, MD PhD; Phone Number: 617-726-8810; Email: BWAINGER@PARTNERS.ORG

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Brian Wainger, MD PhD
      • Sub-Investigator: Marco Loggia, PhD
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Roy Freeman, MD
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Christopher Gilligan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18 to 80
• Capable of providing informed consent and following trial procedures, including capacity to complete self-reported measures of pain, function, and other outcomes
• Stably implanted spinal cord or dorsal root ganglion stimulator
• Device is to treat failed back surgery syndrome with back and radicular lower extremity pain
• Device with a paresthesia-free setting

Exclusion Criteria:

• Patients who are not on a stable dose of opioids or are on a stable dose greater than 100 morphine equivalents/day per day within the two months prior to enrollment, or those who are unwilling to maintain a stable dose of opioids throughout the duration of the study
• The investigator concludes that the participant is unable to differentiate failed back surgery syndrome pain from other pains, or the primary cause of pain is unrelated to failed back surgery syndrome.
• Systemic or psychiatric illness that in the opinion of the site investigator would interfere with the individual's ability to participate in the trial
• Other factor that in the opinion of the site investigator would interfere with the individual's ability to participate in the trial or tolerate the study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients with Implanted Devices on Minimal/No Stimulation Settings; Patients in this arm will be randomized to turn off their spinal cord stimulator (or to minimal settings).	Other: Spinal Cord Stimulator Set to Minimal/No Stimulation Setting; Patients in this intervention group will have their spinal cord stimulator turned off or to the minimal settings possible.
Other: Patients with Implanted Devices on Usual Stimulation Settings; Patients in this arm will be randomized to turn on their spinal cord stimulator to their usual stimulation settings.	Other: Usual Care; Patients in this intervention group will have their spinal cord stimulator turned on to their usual stimulation settings.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Supraexcitability	The primary outcome will be superexcitability (indicating paired pulse facilitation) measured by threshold tracking nerve conduction.	From baseline (enrollment) to six weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Brian Wainger, MD PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: December 14, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 22, 2022

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain
• Other Study ID Numbers: 2022P001803; 1RM1NS128741-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No