Assessing the potential of ivabradine and related drugs for the treatment of nerve pain in patients
| ISRCTN | ISRCTN68734605 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN68734605 |
| Secondary identifying numbers | 32107 |
- Submission date
- 13/03/2017
- Registration date
- 14/03/2017
- Last edited
- 10/08/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
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
Contact information
Public
Box 93
University Division of Anaesthesia
Addenbrooke's Hospital
Cambridge
CB2 0QQ
United Kingdom
 ORCID ID |
0000-0002-5838-2916 |
|---|---|
| Phone | +44 1223 217888 |
| ml404@cam.ac.uk |
Study information
| Study design | Non-randomised; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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 |
| Study acronym | HCN-pain |
| Study objectives | 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(s) | London - Bromley Research Ethics Committee, 07/12/2016, ref: 16/LO/1901 |
| Health condition(s) or problem(s) studied | 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 |
| 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 study start date | 01/12/2015 |
| Completion date | 30/12/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 50; UK Sample Size: 50 |
| Total final enrolment | 7 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 03/04/2017 |
| Date of final enrolment | 30/01/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
Hospital/treatment centre
Box 277, Addenbrookes Hospital
Cambridge
CB2 0QQ
England
United Kingdom
| Phone | +44 1223 256407 |
|---|---|
| r&denquiries@addenbrookes.nhs.uk | |
"ROR" |
https://ror.org/04v54gj93 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/12/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Planned submission to clinically orientated, peer-reviewed journal 12 months after the overall trial end date. |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 18/10/2021 | 08/12/2021 | Yes | No | |
| Protocol file | version 3.0 | 07/02/2018 | 10/08/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
10/08/2022: Uploaded protocol (not peer-reviewed) as an additional file.
08/12/2021: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added.
14/01/2021: The intention to publish date was changed from 30/12/2020 to 30/12/2021.
07/11/2018: The following changes were made:
1. The recruitment end date was changed from 03/10/2018 to 30/01/2019.
2. The overall trial end date was changed from 30/03/2019 to 30/12/2019.
3. The intention to publish date was changed from 30/03/2020 to 30/12/2020.
