Neuropathic Pain MedDRA version: 16.1 Level: LLT Classification code 10054095 Term: Neuropathic pain System Organ Class: 100000004852
Conditions
Interventions
Trade Name: Procorolan
Product Name: Ivabradine
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Ivabradine
CAS Number: 148849-67-6
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Volunteers who have given written informed consent to participate - Volunteers who can communicate fluently in English - Male or female - Aged 18-64 years - Absence of any chronic pain medicine - Volunteers in good general health, including a body mass index (BMI) in the range of 19-35 - Volunteers with a normal resting 12-lead standard ECG including (measured for 1 minute on lead D2): normal sinus rhythm; 60 bpm = HR on resting ECG; PR interval = 210ms; QTcB = 430ms for men and = 450ms for women; QRS duration = 120ms; the results of ECG recordings will be included in the CRF - Women of child bearing potential must use hormonal based contraception for the duration of the trial and 1 week following the end of their trial participation Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 72 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: - Volunteers with 1 arm - Pre-existing pain on either forearm - Previous surgery or tattoo on either forearm - History of disease associated with neuropathy - Volunteers who are allergic to ivabradine or capsaicin - History of personal or familial Long QT Syndrome - History of cardiac dysrhythmia - Use of CYP3A4 inhibitors such as ketoconazole, itraconazole, macrolide antibiotics and the anti-retrovirals nelfinavir, nefazodone and ritonavir. - Use of CYP3A4 inducers (e.g. rifampicin, barbiturates, phenytoin or St John’s Wort etc.) - Use of QT interval prolonging medicinal products (e.g. quinidine, disopyramide or pimozide etc.) - Volunteers with any rash or broken skin on the arm where the capsaicin will be applied - Volunteers with lactose intolerance, as the placebo and ivabradine tablets contain lactose - Volunteers with a resting heart rate of 59 beats per minute or less at screening - Volunteers who are pregnant or breast feeding - Female volunteers of childbearing potential who refuse to use hormonal contraceptive measures for the duration of the trial as listed in section 11.5 of the protocol - Male volunteers who refuse to use adequate contraceptive measures for the duration of the trial as listed in section 11.5 of the protocol - Volunteers who have an underlying medical condition such as migraine or epilepsy which may affect the trial findings - Volunteers who smoke (=5 cigarettes/day), take recreational drugs or consume more than the recommended allowance of alcohol units per week (21 units per week for males and 14 units per week for females) - Participants who are not willing to abstain from drinking beverages containing quinine, caffeine and/or xanthine for 24 hours prior to the trial visit - Volunteers who produce a positive result in a urine screen for drugs of abuse or who are known or suspected to be drug-dependent (sedatives, hypnotics, tranquilizers or any other addictive agent) - Volunteers who produce a positive result in an alcohol breath test - Volunteers currently participating in any interventional trial, have participated in an interventional trial within 16 weeks of screening or are currently participating in a non-interventional trial which participating in this trial would impact upon - Volunteers who, in the opinion of the PI, have a clinically relevant abnormality or medical history that is deemed to make the participant ineligible because of a safety concern.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We will examine whether ivabradine reduces the intensity of sensitisation induced by capsaicin. Application of capsaicin cream to the skin causes a reddening of the skin, and an increased sensitivity within the area the cream is applied (the primary hyperalgesia area) and in surrounding areas (the secondary hyperalgesia area). Changes in sensitivity can be assessed using quantitative sensory testing (QST). This will be an enriched population study, meaning that we will only include participants who respond to capsaicin. This will be determined at the screening visit. The principle research objective is to investigate whether ivabradine reduces the area of secondary punctate mechanical hyperalgesia induced by capsaicin (a change in normal sensation to a von Frey hair or pin prick stimulator).;Secondary Objective: The secondary research objectives will be to determine the effect of ivabradine on secondary hyperalgesia using a variety of other thresholds measured using quantitative sensory testing (QST). The intensity of capsaicin-induced flare will also be assessed using manual tracing, infrared thermography, or laser Doppler imaging. In the primary area we will assess the warm sensation threshold (WST) and the heat pain threshold (HPT). Other thresholds will be determined such as mechanical pain thresholds (MPT) using a weighted hair called a von Frey hair or a pinprick stimulator to apply increasing forces. Thermal and mechanical hyperalgesia will be determined as the change in threshold from baseline to post-capsaicin application, and compared between treatment arms. We will map the area of sensitivity as the area in which volunteers feel changes in normal sensation to light stroking with a cotton bud, soft brush or air puff (known as the area of mechanical allodynia). We will ;Primary end point(s): The primary endpoint is the area of punctate mechanical hyperalgesia in capsaicin-responders. ;Timepoint(s) of evaluation of this end point: Cha | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Endpoints will be summarised for all subjects from data obtained during the screening capsaicin session for standard reference values of capsaicin-induced hyperalgesia and comparison between capsaicin responders and non-responders. Endpoints will be summarised and compared between placebo and ivabradine treatment arms for data obtained during the two trial visits. • Pain score measured using a 100mm visual analogue scale (VAS) • Temperature thresholds in an area of sensitised skin including cold sensation threshold, warm sensation threshold, heat pain threshold and cold pain threshold. Thermal hyperalgesia will be determined as the change in threshold from baseline to post-capsaicin, and compared between treatment arms. • Mechanical thresholds in an area of sensitised skin including mechanical pain threshold. The magnitude of mechanical hyperalgesia will be determined as the change in threshold from baseline to post-capsaicin, and compared between treatment arms • The area of mechanical sensitisation determined using light brushing of the skin (tactile allodynia). ;Timepoint(s) of evaluation of this end point: Change from baseline value (pre-capsaicin) to post-capsaicin value on the screening capsaicin visit. Change from baseline value (pre-capsaicin) to post-capsaicin value (taken 1.5 hours following drug/placebo administration on the two trial visits) | — |
Countries
United Kingdom
Contacts
Public ContactCarrie Bayliss
CCTU Cambridge University Hospitals NHS Foundation Trust
Outcome results
None listed