Plain English Summary
Background and study aims
Neuropathic pain is pain that arises because of nerve damage. Nerves can be damaged by accidental trauma or inadvertently by surgery. Diseases like diabetics or shingles can also cause nerve damage. Not every patient who has nerve damage experiences pain, but those who do suffer from long-term pain that is very challenging and difficult to treat. Scientists in Cambridge have discovered that HCN-2 receptor contributes to pain caused by nerve damage in the laboratory. Drugs have yet to be developed that block the HCN-2 receptor specifically. However, there is already a drug licensed that blocks all types HCN receptors (HCN 1 to 4) called ivabradine. It is currently used to treat patients who have chest pain for heart disease by slowing heart rate. The aim of this study is to find out what effect taking ivabradine has on pain levels in people with neuropathic pain
Who can participate?
Adults with neuropathic pain and no heart problems.
What does the study involve?
All participants receive ivabradine tablets to take twice a day starting at a dose of 2.5mg. The does is then increased every 2-3 weeks if there are no side-effects until the maximum dose of 7.5mg twice a day is reached. Depending on participants’ reaction to the medication, the study lasts for between 14 and 28 days. Every day while they are taking part, participants are asked to rate their pain levels to see if the drug has had any effect.
What are the possible benefits and risks of participating?
There are no direct benefits for patients however this study will help improve understanding about whether HCN channels contributes to nerve pain in humans. The main side effect of ivabradine is slowing of heart rate and so the dose used will be carefully controlled depending on heart rate.
Where is the study run from?
Addenbrookes Hospital (UK)
When is the study starting and how long is it expected to run for?
December 2015 to March 2019
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Dr Michael Lee
ml404@cam.ac.uk
Trial website
Contact information
Type
Public
Primary contact
Dr Michael Lee
ORCID ID
http://orcid.org/0000-0002-5838-2916
Contact details
Box 93
University Division of Anaesthesia
Addenbrooke's Hospital
Cambridge
CB2 0QQ
United Kingdom
+44 1223 217888
ml404@cam.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
32107
Study information
Scientific title
The role of HCN channel receptor in neuropathic pain: An open-label, single arm study of ivabradine in patients with peripheral neuropathic pain
Acronym
HCN-pain
Study hypothesis
The primary hypothesis being tested is that a reduction from baseline in averaged pain scores after treatment with ivabradine in patients with peripheral neuropathic pain.
Ethics approval
London - Bromley Research Ethics Committee, 07/12/2016, ref: 16/LO/1901
Study design
Non-randomised; Interventional; Design type: Treatment, Drug
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Specialty: Anaesthesia, perioperative medicine and pain management, Primary sub-specialty: Anaesthesia, Perioperative Medicine and Pain Management; UKCRC code/ Disease: Neurological/ Nerve, nerve root and plexus disorders
Intervention
All participants receive oral administration of Ivabradine. The dosage of ivabradine will range from 2.5 mg to 7.5 mg twice daily. The starting dose is 2.5mg twice daily for all participants, if tolerated, the dose will be increased every 2-3 weeks by increments of 2.5mg twice daily to a maximum of 7.5mg twice daily.
The study comprises the following visit types
1. Screening
2. Drug initiation
3. Dose adjustments (maximum of 2 occasions)
4. Dose cessation
5. Follow-up
The interval between Screening and Drug Initiation is between 14-28 days. The interval for visit types is 14-21 days. Ivabradine treatment duration is twelve weeks maximum. Dose range is 2.5 to 7.5 mg twice daily.
Intervention type
Other
Phase
Drug names
Primary outcome measure
Daily Pain: Numerical ratings (0=no pain, 10= worst possible pain) scores, recorded daily, starting measured 2 weeks prior to dose initiation till follow-up.
Secondary outcome measures
The following measures are obtained once per visit starting the day before the dose initiation:
1. Overall Pain (between visits) is measured using the Brief Pain Inventory-SF (BPI) questionnaire
2. Sleep is measured using the Insomnia Severity Index (ISI) questionnaire
3. Physical function is measured using the Pain Disability Index (PDI) questionnaire
4. Neuropathic pain sensations are measured using the Neuropathic Pain Symptom Inventory (NPSI) questionnaire
5. Mood is measured using the Depression, Anxiety and Positive Outlook Scale (DAPOS) questionnaire
6. Skin sensitivity is measured using the Sensory scores with punctate and brush stimuli
Overall trial start date
01/12/2015
Overall trial end date
30/12/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Able to give voluntary written informed consent to participate
2. Aged 18 years and above
3. Have peripheral neuropathic pain from diabetes, herpes zoster infection, or trauma to peripheral nerve trunks/plexus (from surgery or physical injury) and DN4 score ≥ 4
4. Have pain for 6 months or more
5. Have pain rated > 4 on a numerical rating scale (NRS) (0= No pain; 10= pain as bad as you can imagine) on at least one Pain sub-item from Brief Pain Inventory
6. Be registered with a GP
7. Have the following findings on standard ECG at screening:
7.1. Normal sinus rhythm (measured for 1 minute on lead II)
7.2. PR interval ≤ 210 ms
7.3. QTcB ≤ 430 ms for men and QTcB ≤ 450 ms for women
7.4. QRS duration ≤ 120 ms
7.5. Heart rate ≥ 60 beats per minute
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 50; UK Sample Size: 50
Participant exclusion criteria
1. Known to be allergic to ivabradine or have hypersensitivity to any of the formulation ingredients
2. Current treatment with ivabradine
3. Use of drugs with potential serious interactions with Ivabradine – as indicated by the latest version of British National Formulary at the time of screening
4. Currently receiving or have received prior to the screening (Visit 1) any of Prohibited Concomitant Medications
5. Have pain rated = 10 a numerical rating scale (NRS) (0= No pain; 10= pain as bad as you can imagine) on ALL pain sub-items from Brief Pain Inventory
6. Scheduled for clinical treatment (e.g. drugs, psychological therapy, surgical or interventional treatment) for any chronic pain or other health condition for the anticipated duration of the study
7. New York Heart Association heart failure class II or higher, or hospitalization for heart failure within a year
8. Myocardial infarct, coronary revascularization, stroke or transient ischemic attack within 6 months of the screening visit
9. Transplanted heart, implanted pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy
10. Scheduled for coronary revascularization; or likely to require cardiac surgery for valvular disease
11. Known congenital long QT, permanent atrial fibrillation or flutter, sick sinus syndrome, sinoatrial block, second and complete atrio-ventricular block
12. Severe or uncontrolled hypertension with systolic BP > 180mmHg or diastolic BP > 110 mmHg after sitting for at least 5 minutes
13. Sitting systolic BP < 85mmHg or symptomatic hypotension
14. Active uncontrolled psychiatric illness (e.g. severe depression (risk of self-harm), schizophrenia, substance misuse or dependence)
15. Known severe renal disease, or moderate or severe liver disease
16. Known to be HIV, Hepatitis B or C seropositive (Level 3 containment laboratory procedures are not available for the handling of infectious specimens)
17. Any illness or condition that in the opinion of the PI or delegated investigators, precludes safe participation in the Study or interferes with Study procedures.
18. Currently participating in any interventional Study, have participated in an interventional Study within 12 weeks of screening or are currently enrolled in a non-interventional Study, which participating in this Study would impact upon
19. Unwilling for the GP to be notified or to provide information relevant to the participation of the clinical Study
20. Transaminases ALT and AST greater than three times the upper normal limit
21. Haemoglobin <11.0g/dL
22. Creatinine clearance (Cockcroft-Gault – section 21.4 of the protocol) < 50 ml/min/1.73m2
23. Females of childbearing potential who decline to use adequate contraceptive measures for the duration of the study
24. Pregnant or breast feeding
Recruitment start date
03/04/2017
Recruitment end date
30/01/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Addenbrookes Hospital
Cambridge University Hospitals NHS Foundation Trust
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
Organisation
Cambridge University Hospitals NHS Foundation Trust
Sponsor details
Box 277
Addenbrookes Hospital
Cambridge
CB2 0QQ
United Kingdom
+44 1223 256407
r&denquiries@addenbrookes.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Research council
Funder name
Medical Research Council
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned submission to clinically orientated, peer-reviewed journal 12 months after the overall trial end date.
Intention to publish date
30/12/2020
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list