NCT05661903

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 180 (estimated)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

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. In a subset of patients we will also perform combined positron emission tomography/magnetic resonance imaging at baseline, week 2 and week 4.

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.

Conditions

• Chronic Pain

Interventions

Type	Name	Description
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	Usual Care	Patients in this intervention group will have their spinal cord stimulator turned on to their usual stimulation settings.
DRUG	Positron Emission Tomography / Magnetic Resonance Imaging	Patients with imaging compatible devices will undergo positron emission tomography/magnetic resonance imaging at three time points during the study. This imaging involves administration of the \[11C\]PBR28 radioligand, which is an investigational drug. Only a subset of patients who have 3 Tesla magnetic resonance imaging compatible stimulators will undergo this imaging.

Timeline

• Start date: 2023-06-08
• Primary completion: 2027-08-31
• Completion: 2027-08-31
• First posted: 2022-12-22
• Last updated: 2025-06-27

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study