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

Bo Biering-Soerensen

Status

Enrolling

Conditions

CRPS (Complex Regional Pain Syndromes)

CRPS (Complex Regional Pain Syndrome) Type I

CRPS Type II

Treatments

Drug: Perineural Incobotulinumtoxin-A 200 U

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT07473635

2024-519832-17-00 (EU Trial (CTIS) Number)

PINCom

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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