Sub-threshold DRG Stimulation vs Sham in Established Responders

Efficacy of Sub-Threshold Dorsal Root Ganglion (DRG) Stimulation Versus Sham in Established Responders: A Randomised, Double-Blind, Two-Period Crossover Trial

The goal of this clinical trial is to learn if sub-threshold dorsal root ganglion (DRG) stimulation provides pain relief beyond placebo in adults with chronic neuropathic pain who already have an implanted DRG stimulator. The main questions it aims to answer are:

• Does sub-threshold DRG stimulation reduce daily pain intensity compared with sham stimulation?
• How does sub-threshold stimulation affect sleep, mood, and daily activity?

Researchers will compare active sub-threshold DRG stimulation to sham (device switched off) to see if stimulation has a genuine effect on pain and wellbeing.

Participants will:

• Be randomly assigned to receive either active sub-threshold DRG stimulation or sham stimulation for 5 days, followed by the opposite condition for another 5 days.
• Complete short electronic diaries twice daily about their pain, sleep, mood, and activity.
• Attend study visits for safety checks and assessments.

Neuropathic pain is a chronic condition that affects 6-10% of adults and is often resistant to conventional drug therapy. The dorsal root ganglion (DRG) has emerged as an important therapeutic target, as abnormal firing in DRG neurons contributes to peripheral and central sensitization. DRG stimulation (DRGS) delivers mild electrical pulses through implanted leads placed near the DRG. Compared with traditional spinal cord stimulation, DRGS provides highly targeted pain relief with fewer unwanted sensations.

Over the past decade, DRGS has become an established treatment for conditions such as complex regional pain syndrome (CRPS), causalgia, chronic low back pain, and post-surgical neuropathic pain. Modern programming favors sub-threshold settings, in which stimulation is delivered below the level that causes tingling sensations (paresthesias). Although widely adopted, the specific contribution of sub-threshold stimulation has never been confirmed in a sham-controlled trial.

This study is the first randomized, double-blind, sham-controlled trial to directly evaluate whether sub-threshold DRG stimulation provides pain relief beyond placebo. Adults with an implanted DRG stimulator who have shown sustained pain relief will be randomized in a two-period crossover design to receive either active sub-threshold stimulation or sham stimulation, each for 5 days, with a washout period in between.

The primary objective is to determine whether sub-threshold DRG stimulation reduces mean daily pain intensity compared with sham. Secondary objectives include assessing sleep quality, mood, daily activity, and safety/tolerability. Exploratory measures include device logs and rescue medication use.

The findings of this trial will provide critical evidence on the efficacy of sub-threshold DRG stimulation, helping to inform clinical guidelines, payer decisions, and neuromodulation programming strategies worldwide.

Inclusion Criteria:

• Adults, age 18 years or older
• Implanted with a dorsal root ganglion (DRG) stimulator for chronic neuropathic pain
• Have experienced at least 50% reduction in pain for 3 months or longer on standard DRG therapy
• Stable pain medication regimen for at least 4 weeks before enrollment
• Able and willing to complete electronic diaries and attend study visits

Exclusion Criteria:

• Active infection or wound complication at the stimulator implant site
• Significant psychiatric illness (for example, uncontrolled depression or psychosis)
• Planned surgery, device reprogramming, or medication changes during the study period
• Currently pregnant or breastfeeding
• Occurrence of any adverse event that meets predefined withdrawal criteria during the study (such as intolerable pain or device-related complications)