The influence of ivabradine in a healthy volunteer pain model

• Register: ISRCTN
• Last refreshed on: 6 January 2020
• Main ID: ISRCTN97420179
• Date of registration: 31/07/2014
• Prospective Registration: No
• Primary sponsor: Cambridge University Hospitals NHS Foundation trust & University of Cambridge (UK)
• Public title: The influence of ivabradine in a healthy volunteer pain model
• Scientific title: A randomised, double-blind, placebo-controlled crossover study of the influence of the HCN channel blocker ivabradine in a healthy volunteer pain model - an enriched population study
• Date of first enrolment: 14/07/2014
• Target sample size: 24
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN97420179
• Study type: Interventional
• Study design: Randomised; Interventional; Design type: Not specified, Screening (Other)
• Phase: Not Applicable

Countries of recruitment

United Kingdom

Contacts

• Name: Michael Lee

Key inclusion & exclusion criteria

Inclusion criteria:
1. Volunteers who have given written informed consent to participate
2. Volunteers who can communicate fluently in English
3. Male or female
4. Aged 18-64 years
5. Absence of any chronic pain medicine
6. Volunteers in good general health, including a body mass index (BMI) in the range of 19-35
7. 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 = 210 ms; QTcB = 430 ms for men and = 450 ms for women; QRS duration = 120 ms; the results of ECG recordings will be included in the CRF
8. Women of childbearing potential must use hormonal-based contraception for the duration of the trial and 1 week following the end of their trial participation

Exclusion criteria:
1. Volunteers with one arm
2. Pre-existing pain on either forearm
3. Previous surgery or tattoo on either forearm
4. History of disease associated with neuropathy
5. Volunteers who are allergic to ivabradine or capsaicin
6. History of personal or familial Long QT Syndrome
7. History of cardiac dysrhythmia
8. Use of CYP3A4 inhibitors such as ketoconazole, itraconazole, macrolide antibiotics and the anti-retrovirals nelfinavir, nefazodone and ritonavir
9. Use of CYP3A4 inducers (e.g. rifampicin, barbiturates, phenytoin or St John?s Wort etc.)
10. Use of QT interval prolonging medicinal products (e.g. quinidine, disopyramide or pimozide etc.)
11. Volunteers with any rash or broken skin on the arm where the capsaicin will be applied
12. Volunteers with lactose intolerance, as the placebo and ivabradine tablets contain lactose
13. Volunteers with a resting heart rate of 59 beats per minute or less at screening
14. Volunteers who are pregnant or breastfeeding
15. 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
16. Male volunteers who refuse to use adequate contraceptive measures for the duration of the trial as listed in section 11.5 of the protocol
17. Volunteers who have an underlying medical condition such as migraine or epilepsy which may affect the trial findings
18. 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)
19. Participants who are not willing to abstain from drinking beverages containing quinine, caffeine and/or xanthine for 24 hours prior to the trial visit
20. 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)
21. Volunteers who produce a positive result in an alcohol breath test
22. 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
23. 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


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Topic: Anaesthesia, perioperative medicine and pain management; Subtopic: Anaesthesia, perioperative medicine and pain management; Disease: All Anaesthesia, perioperative medicine and pain management
Signs and Symptoms

Intervention(s)

This is a crossover trial such that every participant will receive one dose of ivabradine (15 mg Procoralan, oral tablets) and one dose of matching placebo (15 mg) ? the order of administration (ivabradine followed by placebo or placebo followed by ivabradine) will be randomised (and double-blinded). Following completion of the three visits, no follow-up is planned for the volunteers (unless a participant has experienced a serious side effect as a result of the study, in which case a doctor will follow-up the participant until the side effect has stabilised or resolved).

Primary Outcome(s)

The area of punctate mechanical hyperalgesia in capsaicin responders

Secondary Outcome(s)

Not provided at time of registration

Secondary ID(s)

2012-005627-32

16773

Source(s) of Monetary Support

Medical Research Council (MRC) (UK); Grant Codes: MR/J013129/1

Ethics review

Status:
Approval date:
Contact:

14/EE/0132; First MREC approval date 12/06/2014

Results

• Results available: Yes
• Date Completed: 01/12/2015