Perineural Incobotulinumtoxin-A for Complex Regional Pain Syndrome - An Open-label Feasibility Study

Official title

Perineural Incobotulinumtoxin-A for Complex Regional Pain Syndrome - An Open-label Feasibility Study (PINCom)

Overview

Complex Regional Pain Syndrome (CRPS) is a chronic pain condition characterized by severe regional pain, sensory disturbances, and functional impairment. Current treatment options are limited, and many patients experience substantial pain-related disability and symptom fluctuations, including flare-ups triggered by invasive procedures. Perineural administration of botulinum toxin A has shown analgesic effects in other neuropathic pain conditions and may represent a less painful alternative to subcutaneous injection techniques. However, the feasibility, tolerability, and safety of perineural botulinum toxin administration in patients with CRPS have not been systematically evaluated. The PINCom study is a single-center, open-label feasibility study designed to assess the safety, tolerability, and practical feasibility of ultrasound-guided perineural injection of incobotulinumtoxin-A in patients with unilateral chronic CRPS affecting an upper or lower limb. Participants receive a single perineural injection targeting major sensory nerves supplying the affected limb and are followed for 12 weeks. Primary outcomes focus on feasibility metrics, including recruitment, retention, adherence, and data completeness, as well as safety outcomes, including serious adverse events and procedure-related complications. Tolerability is assessed through monitoring of CRPS flare-ups and a dedicated qualitative interview exploring participant experience. Exploratory outcomes include pain intensity, CRPS severity, and patient-reported measures collected to inform the design of a future randomized controlled trial.

Detailed description

The PINCom study is a single-center, open-label feasibility study designed to evaluate the practical feasibility, safety, and tolerability of ultrasound-guided perineural injection of incobotulinumtoxin-A in adults with unilateral CRPS of an upper or lower limb. Depending on the anatomical distribution of symptoms, injections are administered at the supraclavicular brachial plexus (upper limb) or at distal sciatic and/or femoral nerve targets (lower limb). All procedures are performed under ultrasound guidance in a single treatment session.

The primary objective of the study is to determine whether a larger randomized controlled trial of perineural incobotulinumtoxin-A in CRPS is feasible at the study center. Feasibility outcomes include recruitment rate, screening-to-enrollment ratio, retention, adherence to study visits and daily pain diary completion, and completeness of outcome data.

Safety is assessed through monitoring of serious adverse events and targeted screening for procedure-related complications, potential nerve injury, and signs of systemic botulinum toxin spread. Adverse events are recorded throughout the study period. Given the clinical characteristics of CRPS, flare-ups are monitored separately as a tolerability outcome rather than as a primary safety endpoint.

Tolerability and participant experience are evaluated using a combination of structured symptom monitoring and a semi-structured qualitative interview conducted during follow-up. The interview explores participants' experiences of the injection procedure, perceived burden of study participation, and acceptability of the intervention. This qualitative component is intended to inform protocol refinement and patient-centered trial design.

Exploratory clinical outcomes are collected to characterize symptom variability and inform future trial design. These include daily pain intensity ratings, CRPS Severity Score assessments, sensory symptom mapping, and patient-reported outcome measures assessing pain quality, psychological factors, physical function, and quality of life. These measures are not powered to assess efficacy but will be used to estimate variability and optimal outcome timing for a future definitive trial.

Participants are followed for 12 weeks after treatment. Findings from this feasibility study will be used to guide decisions regarding the design, outcome selection, and operational aspects of a subsequent randomized controlled trial evaluating perineural incobotulinumtoxin-A for the treatment of CRPS.

Interventions

• Drug Perineural Incobotulinumtoxin-A 200 U
  Single perineural injection of 200 U iBonT-A around the brachial plexus in the case of upper limb CRPS, or 150 U iBonT-A around the distal ischial nerve and 50 U around the saphenus nerve in the case of lower limb CRPS.

Primary outcome measures

• Recruitment rate [Time frame: From study start through Day 84 (12 weeks)]
• Screening-to-enrolment ratio [Time frame: From study start through Day 84]
• Study completion rate [Time frame: Day -7 to 84]
• Completeness of study data [Time frame: Day -7 to 84]

Secondary outcome measures (3)

• Serious Adverse Events (SAEs) [Time frame: From treatment (Day 0) through Day 84]
• CRPS flare-ups [Time frame: From treatment (Day 0) through Day 84]
• Participant-reported acceptability and experience [Time frame: From enrolment to day 42]

Eligibility criteria

Inclusion criteria

• Are over the age of 18
• Have a diagnosis of CRPS type 1 or 2 in either one upper or one lower extremity which fulfils the Budapest research criteria
• Have had the condition for at least 6 months
• Rate CRPS as their primary pain condition
• Have been on a stable analgesic regimen, including any rescue medications, for at least 1 month prior to the study and intend to maintain this regimen throughout the study
• For pre-menopausal females: are using a safe and approved contraceptive
• Speak, read, and understand Danish

Exclusion criteria

• Are allergic to botulinum toxin A
• Have been treated with botulinum toxin A for any indication within 3 months prior to study start
• Are diagnosed with myasthenia, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other condition which makes differentiation of CRPS-specific pain difficult
• Have an ongoing infection in the affected limb
• Do not intend to start physical therapy, psychotherapy, or any other non-pharmaceutical intervention aimed at reducing pain
• Have used a topical analgesic treatment such as lidocaine patches within 1 week prior to study start or have been treated with capsaicin patches in the affected area within 3 months prior to study start
• Have psychiatric comorbidities which are considered by the investigators to impact their ability to participate
• Consume alcohol in excess of what is recommended by the Danish Health Ministry
• Are active abusers of illicit narcotics
• Are pregnant, lactating, or plan on becoming pregnant during the study period
• Have any other condition or circumstance that, in the investigators' opinion, will hinder safe and timely participation and completion of the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

Denmark · 1 center

• CRPS- and Nerve Pain Clinic, Rigshospitalet Glostrup — Glostrup

Identifiers

NCT: NCT07473635 · PINCom · 2024-519832-17-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗