Chronic PainPhase 2NCT05661903
From Nerve to Brain: Toward a Mechanistic Understanding of Spinal Cord Stimulation in Human Subjects
A Phase 2 study testing Spinal Cord Stimulator Set to Minimal/No Stimulation Setting and Positron Emission Tomography / Magnetic Resonance Imaging in people with Chronic Pain, run by Massachusetts General Hospital at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Pain
- What is being tested?
- Spinal Cord Stimulator Set to Minimal/No Stimulation Setting and Positron Emission Tomography / Magnetic Resonance Imaging
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 3 sitesUnited States
- Study dates
- 8 Jun 2023to 31 Aug 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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).
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brian Wainger, MD PhD
Marco Loggia, PhD
- Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Roy Freeman, MD
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02215
Christopher Gilligan, MD
About this study
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.
Read the 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
- Being tested
- Spinal Cord Stimulator Set to Minimal/No Stimulation Setting, Usual Care, Positron Emission Tomography / Magnetic Resonance Imaging
- Medical subject headings
- Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Spinal Cord Stimulator Set to Minimal/No Stimulation SettingOther
Patients in this intervention group will have their spinal cord stimulator turned off or to the minimal settings possible.
Usual CareOther
Patients in this intervention group will have their spinal cord stimulator turned on to their usual stimulation settings.
Positron Emission Tomography / Magnetic Resonance ImagingDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: Other: Usual Care; Drug: Positron Emission Tomography / Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Supraexcitability
The primary outcome will be superexcitability (indicating paired pulse facilitation) measured by threshold tracking nerve conduction.
Measured: From baseline (enrollment) to six weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2022
- Study start8 Jun 2023
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian Wainger, Massachusetts General Hospital
- Investigators
- Brian Wainger, MD PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05661903
- Sponsor's protocol ID
- 2022P001803
- Other IDs
- 1RM1NS128741-01
- Status last verified
- Aug 2026
- First submitted
- 14 Dec 2022
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- From Nerve to Brain: Toward a Mechanistic Understanding of Spinal Cord Stimulation in Human Subjects
- ClinicalTrials.gov ID
- NCT05661903
- Acronym / sponsor ID
- 2022P001803
- Conditions
- Chronic Pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 8 Jun 2023 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 22 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with Implanted Devices on Minimal/No Stimulation Settings | Other | Other: Spinal Cord Stimulator Set to Minimal/No Stimulation Setting, Drug: Positron Emission Tomography / Magnetic Resonance ImagingPatients in this arm will be randomized to turn off their spinal cord stimulator (or to minimal settings). |
| Patients with Implanted Devices on Usual Stimulation Settings | Other | Other: Usual Care, Drug: Positron Emission Tomography / Magnetic Resonance ImagingPatients in this arm will be randomized to turn on their spinal cord stimulator to their usual stimulation settings. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Spinal Cord Stimulator Set to Minimal/No Stimulation SettingPatients in this intervention group will have their spinal cord stimulator turned off or to the minimal settings possible. | Other | Patients with Implanted Devices on Minimal/No Stimulation Settings |
| Usual CarePatients in this intervention group will have their spinal cord stimulator turned on to their usual stimulation settings. | Other | Patients with Implanted Devices on Usual Stimulation Settings |
| Positron Emission Tomography / Magnetic Resonance ImagingPatients 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. | Drug | Patients with Implanted Devices on Minimal/No Stimulation Settings, Patients with Implanted Devices on Usual Stimulation Settings |
Primary outcome
Supraexcitability
Time frame: From baseline (enrollment) to six weeks
The primary outcome will be superexcitability (indicating paired pulse facilitation) measured by threshold tracking nerve conduction.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Brian Wainger, MD PhD principal investigator
Massachusetts General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Spinal Cord Stimulator Set to Minimal/No Stimulation Setting and Positron Emission Tomography / Magnetic Resonance Imaging in people with Chronic Pain, run by Massachusetts General Hospital at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Brian Wainger, MD PhD (617-726-8810, BWAINGER@PARTNERS.ORG), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Supraexcitability (time frame: From baseline (enrollment) to six weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026.