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

NCT05661903 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2022P0018031RM1NS128741-01
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Chronic Pain

Outcome Measures

Primary Outcomes (1)

• Supraexcitability

  The primary outcome will be superexcitability (indicating paired pulse facilitation) measured by threshold tracking nerve conduction.

  From baseline (enrollment) to six weeks

Study Arms (2)

Patients with Implanted Devices on Minimal/No Stimulation Settings

OTHER

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; Drug: Positron Emission Tomography / Magnetic Resonance Imaging

Patients with Implanted Devices on Usual Stimulation Settings

OTHER

Patients in this arm will be randomized to turn on their spinal cord stimulator to their usual stimulation settings.

Other: Usual Care; Drug: Positron Emission Tomography / Magnetic Resonance Imaging

Interventions

Spinal Cord Stimulator Set to Minimal/No Stimulation Setting OTHER

Patients in this intervention group will have their spinal cord stimulator turned off or to the minimal settings possible.

Patients with Implanted Devices on Minimal/No Stimulation Settings

Usual Care OTHER

Patients in this intervention group will have their spinal cord stimulator turned on to their usual stimulation settings.

Patients with Implanted Devices on Usual Stimulation Settings

Positron Emission Tomography / Magnetic Resonance Imaging DRUG

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.

Patients with Implanted Devices on Minimal/No Stimulation Settings; Patients with Implanted Devices on Usual Stimulation Settings

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 back/radicular lower extremity pain or neck/arm pain
• Device with a paresthesia-free setting

You may not qualify if:

• Patients who are not on a stable dose of opioids or are on a stable dose greater than 100 MME/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 back or neck/arm pain from other pains
• 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
• Dropout Criteria for Optional Imaging
• Stimulation device is not 3 Tesla magnetic resonance imaging compliant
• Contraindications to magnetic resonance imaging and/or positron emission tomography scanning (including presence of a cardiac pacemaker or pacemaker wires, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia)
• Pregnant or breastfeeding
• Participants with a low affinity binder phenotype based off testing for the Ala147Thr polymorphism.
• Current or recent use of benzodiazepines (except for alprazolam, clonazepam, and lorazepam). Recent use will be defined based off the benzodiazepines half-life, such that patients who stopped taking the medication at least five half-lives ago will be considered eligible for scanning.
• Subjects who have exceeded (or would exceed if they were to participate) the yearly amount of allowable radiation, as defined by the Radiation Safety Committee
• In the opinion of the investigators, unable to safely participate in this study and/or provide reliable data (e.g., unlikely to remain still during the imaging procedures).

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Chronic Pain

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Brian Wainger, MD PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brian Wainger, MD PhD

CONTACT

617-726-8810; BWAINGER@PARTNERS.ORG

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor in Anesthesiology and Neurology

Study Record Dates

• First Submitted: December 14, 2022
• First Posted: December 22, 2022
• Study Start: June 8, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

US (3)