CAT-Trial: CGRP monoclonal Antibody for Treatment of painful diabetic neuropathy: a double-blind, multicenter, placebo-controlled, international phase II clinical trial

Who can take part

• Age 18 – 75 years
• Confirmed diagnosis of probable diabetic polyneuropathy, as defined by the Toronto consensus criteria and a TCNS > 5 or abnormal DPNCheck or abnormal NCS
• Probable neuropathic pain as defined by the NeuPSIG guidelines
• Symmetric distal pain worse in the distal lower extremities present for >6 months
• Average pain score on a NRS of ≥4 during the baseline week

Who cannot take part

• Prior or current use of a CGRP mAbs or CGRP antagonists
• Planned larger surgery in the treatment period
• Lifetime history of psychosis, bipolar mania, or dementia. Patients with other psychiatric conditions whose symptoms are not controlled or who have not been adequately treated for a minimum of 6 months prior to screening are also excluded
• Initiation of new neuropathic pain medications such as gabapentinoid medications (gabapentin, pregabalin) and/or capsaicin (Quetenza), botulinum toxin type A, serotonin/norepinephrine reuptake inhibitors (TCA or duloxetine or venlafaxine) 1 month prior to enrollment or for the duration of the randomized placebo-controlled phase of the study. Current and ongoing pain treatment will be allowed in stable dose (anticonvulsants, antidepressants, tramadol, topical treatments (excluding high dose capsaicin patch and botulinum toxin type A) (Paracetamol 1g and over-the-counter NSAIDS as needed up to four times daily are allowed as rescue medicine)
• Suspected cause of lower extremity pain of other causes than diabetes (e.g. chemotherapy, alcohol or drug misuse, vitamin deficiency, concomitant central nervous system pathology) or patients with pain that cannot be distinguished from their neuropathic pain in the feet due to diabetes
• The patient has a history of clinically significant cardiovascular disease, including uncontrolled hypertension, ischaemia or thromboembolic events (for example, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism)
• Peripheral arterial disease (PAD) defined as toe pressure <40mmHg, no palpable foot pulses or clinical claudicatio intermittens
• All female subjects of childbearing potential must have negative result of a serum pregnancy test performed at screening. Subjects of childbearing potential must agree to use a medically approved form of birth control (abstinence, intrauterine device (IUD), oral contraception, barrier and spermicide or hormonal implant) throughout the duration of the study
• Chronic wounds
• Unable to understand Danish (Danish site only)
• Pregnant or planning to become pregnant during the duration of the study
• Opioid regimen other than stable low dose of Tramadol (maximum 200 mg/day)
• BMI ≥39 kg/m2 at the screening visit