Complex Regional Pain Syndromes, Neuralgia
Conditions
Brief summary
The purpose of this study is to determine whether the EGFR-inhibitor cetuximab is better than placebo for the treatment of neuropathic pain.
Interventions
DRUGCetuximab
Randomized cross-over between cetuximab and placebo
DRUGPlacebo
Randomized cross-over between cetuximab and placebo
Sponsors
Frontier Science & Technology Research Foundation, Inc.
Merck KGaA, Darmstadt, Germany
Sorlandet Hospital HF
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent and anticipated compliance. * Pain defined as definite neuropathic pain, according to the Special Interest Group on Neuropathic Pain guidelines or defined as probable NP, according to the guidelines, if the confirmatory test was a positive diagnostic test. Complex regional pain syndrome can be included despite lack of an offending lesion, as long as the Budapest criteria are fulfilled * Neuropathic Pain associated with compressive nerve states (including failed surgery) or CRPS (according to the Budapest criteria) * PainDETECT score of at least 13 with average pain intensity of at least 6 /10 over the last four weeks. In addition, a painDETECT pattern indicating that the underlying neuropathic pain is constantly present. * Worst pain intensity higher than 6 for five of seven days during the screening phase, according to Brif Pain Inventory. * The patient should be able to distinguish between the neuropathic pain and other pain conditions, including elements of nociceptive pain caused by the same disease process. * Neuropathic pain duration of between six and thirty months, deemed chronic and likely to be irreversible by clinical history and findings. * No new or increased neuropathic pain treatment for the last four weeks. * Standard medical treatments for the patients' underlying condition or neuropathic pain must have been considered or tried and must, according to the opinion of the referring or a consulted pain specialist, be judged to be inappropriate or of insufficient potential efficacy. * Referring physician agreement to follow up the patient after study completion according to the best possible and available pain treatment and care. * Women of childbearing potential and men must use an acceptable method of contraception throughout the study, and for 30 days after the last study drug administration. * Negative pregnancy test within 7 days before each treatment period where appropriate. * White blood cell count ≥ 3 × 109 with neutrophils ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L and hemoglobin ≥ 6.21 mmol/L (10 g/dL). Total bilirubin ≤ 1.5 × upper limit of reference range and AST and ALT ≤ 2.5 × upper limit of reference range within the last 28 days before inclusion. * Aged 18 or above
Exclusion criteria
* Neuropathic pain origin in the central nervous system. * Phantom limb pain or a significant component of nociceptive pain. * Ascending distal small fiber peripheral neuropathy. * Patients primarily experiencing pain 'attacks', i.e. pattern of neuropathic pain depicted in picture 3 of the painDETECT. * Other pain state that may interfere with evaluation of the studied neuropathic pain condition. * Any underlying medical or psychiatric condition, clinical disorder or laboratory finding, which in the opinion of the investigator may interfere with study objectives. * Uncontrolled or unstable diabetes. * Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV), unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias * Severe cerebrovascular disease during the six months prior to inclusion. * Active and ongoing eye and skin disorders or newly diagnosed gastric ulcer that may interfere with the study treatment. * History of allergic reaction to any of the study treatment components, red meat or tick bites. * Previous treatment with any EGFR-pathway inhibitor. * Women who are pregnant or breastfeeding. * Participation in another clinical trial within the past 90 days. * Use of any investigational agent within 90 days prior to day 1 of study drug. * Known drug abuse/alcohol abuse, legal incapacity or limited legal capacity or any other reason that, in the opinion of the investigator precludes the subject from participating.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in average neuropathic pain score using an 11-point numeric rating scale. | Days 4-8 after each infusion of cetuximab and placebo |
Secondary
| Measure | Time frame |
|---|---|
| Comparison of frequency, in all patients on active treatment of at least a 30% reduction of average neuropathic pain score using an 11-point numeric rating scale. | Days 4-8 after each infusion of cetuximab and placebo |
| Comparison of frequency in all patients on active treatment of at least a 50% reduction of average neuropathic pain score using an 11-point numeric rating scale. | Days 4-8 after each infusion of cetuximab and placebo |
| Comparison of change in average worst neuropathic pain score using an 11-point numeric rating scale. | Days 4-8 after each infusion of cetuximab and placebo |
| Comparison of frequency in all patients on active treatment of at least a 50% reduction of average worst neuropathic pain score using an 11-point numeric rating scale. | Days 4-8 after each infusion of cetuximab and placebo |
| Comparison of frequency, in all patients on active treatment of at least a 30% reduction of average worst neuropathic pain score using an 11-point numeric rating scale. | Days 4-8 after each infusion of cetuximab and placebo |
| Brief Pain Iinventory (short form) interference scores, comparing cetuximab to the placebo. | Days 4-8 after each infusion during treatment periods 1 and 2. |
| Brief Pain Iinventory (short form) total scores, comparing cetuximab to the placebo. | Days 4-8 after each infusion during treatment periods 1 and 2. |
| 2-hourly waking time 11-point numeric rating scale (item #6 from the Brief Pain Inventory) in the first 24 hours and daily thereafter. | 2-hourly in first 24 hours after infusion and daily thereafter until end of study (day 86). |
| Number of AE and SAE recording | From signing informed consent (within 28 days prior to first study treatment) and until 30 days after the last study infusion. |
| Patient Global Impression of Change. | 7 days after each infusion. |
Countries
Norway
Outcome results
None listed