Evaluation of Pain Medication Tapering Protocols in Persistent Spinal Pain Syndrome Type II Patients Undergoing Spinal Cord Stimulation: Buprenorphine, Naloxone, Oxycodone, and Clonidine

The primary objective of this study is to evaluate the impact of different **pain medication tapering** protocols on disability outcomes in patients with **Persistent Spinal Pain Syndrome Type II (PSPS T2)** undergoing **Spinal Cord Stimulation (SCS)**. Specifically, the study aims to determine whether there is a difference in disability after 12 months of SCS among patients who received a standardized pain medication tapering protocol, a personalized pain medication tapering protocol, or no tapering protocol prior to SCS implantation. This objective is clinically relevant as it seeks to optimize preoperative pain management strategies to improve long-term functional outcomes in PSPS T2 patients.

The clinical trial involves participants diagnosed with **Persistent Spinal Pain Syndrome Type II (PSPS T2)**, characterized by neuropathic pain of radicular origin in the lower back and/or legs. The study population includes both male and female subjects aged 18 years and older. Participants are required to have experienced pain of at least 4/10 on the Numeric Rating Scale for a minimum of six months following at least one anatomically successful spinal surgery, and they must be refractory to conservative treatment. All participants are scheduled for spinal cord stimulation (SCS) and are currently taking opioids. The trial does not include a vulnerable population, and participants must be able to speak and read Dutch or French. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the impact of different pain medication tapering protocols on disability outcomes in patients with **Persistent Spinal Pain Syndrome Type II (PSPS T2)** undergoing Spinal Cord Stimulation (SCS). This study employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The trial is expected to span a duration of approximately three years, with an estimated end date in October 2026. Participants will be randomly assigned to one of three groups: a standardized pain medication tapering protocol, a personalized tapering protocol, or no tapering protocol prior to SCS implantation. The primary endpoint is the change in the Oswestry Disability Index score 12 months post-SCS implantation, analyzed using a longitudinal mixed model with assessments at baseline, 1 month, 3 months, 6 months, and 12 months.

Study visits are structured to include an initial screening visit to confirm eligibility, followed by regular follow-up visits at specified intervals to monitor progress and collect data. The inclusion visit will assess the patient's diagnosis of PSPS T2, pain intensity, previous spinal surgery, and language proficiency, among other criteria. Follow-up visits will occur at 1, 3, 6, and 12 months post-SCS implantation to evaluate the primary and any secondary outcomes. The end-of-study visit will coincide with the final 12-month assessment, concluding the participant's involvement in the trial.

Participants are expected to be involved in the study for a total of 12 months post-SCS implantation, with the entire trial duration extending to the estimated end date. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any adverse events that compromise participant safety. The trial is categorized as a phase IV, low-intervention study, reflecting its focus on post-marketing surveillance and the evaluation of treatment protocols in a real-world setting.

The clinical trial involves the administration of several **experimental medications**. The first medication is Suboxone, available in two formulations: 2 mg/0.5 mg and 8 mg/2 mg sublingual tablets. Each tablet contains **buprenorphine** and **naloxone** as active substances. The pharmaceutical form is a sublingual tablet, and the route of administration is sublingual. The maximum daily dose is 36 mg, with a total maximum dose of 13062 mg over a treatment period of up to 12 months. The medication is manufactured by Indivior Europe Limited.

Another medication used in the trial is OxyNorm Instant, which is available in three dosages: 5 mg, 10 mg, and 20 mg orodispersible tablets. The active substance in these tablets is **oxycodone hydrochloride**. The pharmaceutical form is an orodispersible tablet, administered orally. The maximum daily dose is 80 mg, with a total maximum dose of 400 mg over a treatment period of up to 5 days. This medication is produced by Mundipharma Comm VA and Mundipharma BV.

Catapressan is also included in the trial, available as a 150 microgram solution for injection/infusion and as 150 microgram tablets. The active substance is **clonidine hydrochloride**. The solution is administered intravenously, while the tablets are taken orally. The maximum daily dose for the solution is 1200 micrograms, with a total maximum dose of 5400 micrograms over 8 days. For the tablets, the maximum daily dose is 600 mg, with a total maximum dose of 11100 mg over 4 days. Glenwood GmbH manufactures this medication.

Additionally, Libroxar is used in the trial, available in two formulations: 2 mg/0.5 mg and 8 mg/2 mg sublingual tablets. The active substances are **buprenorphine** and **naloxone**. The pharmaceutical form is a sublingual tablet, administered sublingually. The maximum daily dose is 36 mg, with a total maximum dose of 13062 mg over a treatment period of up to 12 months. This medication is produced by Laboratoires SMB S.A.

Throughout the trial, participant compliance with the dosing schedules is monitored to ensure adherence to the prescribed treatment regimens. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data provided.

Efficacy in the clinical trial will be assessed by evaluating the primary endpoint, which is the difference in the Oswestry Disability Index (ODI) score among patients with Persistent Spinal Pain Syndrome Type II (PSPS T2) 12 months after definitive Spinal Cord Stimulation (SCS) implantation. The trial will compare three groups: those receiving a standardized pain medication tapering protocol, a personalized pain medication tapering protocol, and no tapering protocol before SCS implantation. The ODI is a widely used tool for measuring disability related to spinal disorders, providing a quantifiable measure of the impact of pain on daily activities.

The efficacy parameters will be collected and analyzed using a longitudinal mixed model analysis. Measurements will be taken at multiple timepoints: baseline, 1 month, 3 months, 6 months, and 12 months post-SCS implantation. This approach allows for the assessment of changes over time and the comparison of outcomes between the different intervention groups. The use of the ODI as a validated scale ensures the reliability and validity of the efficacy assessments in this trial.