The formation of carbamazepine metabolites and carbamazepine-protein conjugates in epilepsy patients
| ISRCTN | ISRCTN62125126 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN62125126 |
| Clinical Trials Information System (CTIS) | 2013-002743-28 |
| Protocol serial number | 15543 |
| Sponsor | University of Liverpool |
| Funder | Medical Research Council |
- Submission date
- 18/02/2015
- Registration date
- 19/02/2015
- Last edited
- 21/09/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Carbamazepine is an effective drug that is used in the treatment of epilepsy, neuralgia and psychiatric disorders. Although generally well tolerated, it can cause hypersensitivity reactions such as a skin rash in up to 10% of patients. These reactions can result in hospital admission, long-term complications such as blindness, and can cause death in up to 30% of patients. These reactions are caused by the immune system. Recent research has identified that patients with specific genes are at a higher risk of developing this hypersensitivity. Carbamazepine is converted by the liver to other chemical products called metabolites. It is believed that one or more of these metabolites activate the immune system. However, it is not known how this happens. This aim of this study is to assess the stable and toxic products formed in the blood and urine of patients receiving carbamazepine.
Who can participate?
Adults aged at least 18 who have either just been prescribed carbamazepine or have received the treatment at the same dose for at least 4 weeks
What does the study involve?
Participants provide blood and urine samples in order to identify the chemicals responsible for triggering the immune system in susceptible people. Genetic variations are also analysed to determine their effects on carbamazepine.
What are the possible benefits and risks of participating?
These results may help to explain the variation in carbamazepine hypersensitivity between patients. Lessons learned from this research will provide valuable information for other drugs that cause similar hypersensitivity reactions (e.g. penicillins). Improved understanding of the mechanism of carbamazepine hypersensitivity will enable safer drug design in future and the development of predictive tests that can diagnose and identify patients susceptible to adverse reactions.
Where is the study run from?
University of Liverpool (UK)
When is the study starting and how long is it expected to run for?
November 2013 to April 2015
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Dr Vincent Yip
Contact information
Scientific
University of Liverpool
Wolfson Centre for Personalised Medicine
Department of Pharmacology
Block A: Waterhouse Buildings
1–5 Brownlow Street
Liverpool
L69 3GL
United Kingdom
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Non-randomised; Both; Treatment |
| Secondary study design | Non randomised study |
| Study type | Participant information sheet |
| Scientific title | A pharmacokinetic investigation into the formation of carbamazepine metabolites and carbamazepine-protein conjugates in epilepsy patients |
| Study acronym | PICME II |
| Study objectives | This study aims to improve our mechanistic understanding of carbamazepine hypersensitivity by using high sensitivity mass spectrometry to characterise and quantify the stable and toxic products formed in the blood and urine of patients receiving carbamazepine therapy. |
| Ethics approval(s) | 13/NW/0503 |
| Health condition(s) or problem(s) studied | Topic: Neurological; Subtopic: Neurological (all Subtopics); Disease: Epilepsy |
| Intervention | Patients in the auto-induction group will be newly prescribed carbamazepine. All other subjects in the study will have been prescribed carbamazepine by their neurologist as part of clinical care for patient for at least 4 weeks. |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Carbamazepine |
| Primary outcome measure(s) |
Pharmacokinetic analyses; Timepoint(s): Time points dependent on time of presentation to clinic |
| Key secondary outcome measure(s) |
N/A |
| Completion date | 30/04/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 158 |
| Key inclusion criteria | Autoinduction group: 1. Subject is willing and able to give written informed consent 2. Subject is aged 18 or over 3.Subject is newly prescribed carbamazepine by their attending physician Maintenance group: 1. Subject is willing and able to give written informed consent 2. Subject is aged 18 or over 3. Subject has received CBZ therapy at the same dosage for at least 4 weeks |
| Key exclusion criteria | Autoinduction group: 1. Subject is not willing to take part or unable to give written informed consent 2. Subject has in the past 4 weeks received other medication that is a CYP3A4 inducer or inhibitor (see medications below) 3. Subject has taken part on another research study within 90 days of commencement 4. Subject has any condition which in the opinion of the investigator will interfere with the study Excluded medications: Rifampicin, Amiodarone, Fluvoxamine, Saquinavir, Rifampin, Amprenavir, Indinavir, SVerapamil, Isoniazid, Atazanavir, Lopinavir, Verapamil, Phenytoin, Azithromycin, Mifepristone, Phenobarbital, Grapefruit juice, Nelfinavir, Omeprazole, Clarithromycin, Norverapamil, Clotrimazole, Cyclosporine A, Ritonavir, HMGCoA reductase inhibitors, Delavirdine, Ndesmethylerythromycin, Cyclophosphamide, Erythromycin, Roxithromycin, Spironolactone, Fluoxetine, RVerapamil Maintenance group: 1. Subject is not willing to take part or unable to give written informed consent 2. Subject has any condition which in the opinion of the investigator will interfere with the study |
| Date of first enrolment | 05/11/2013 |
| Date of final enrolment | 30/04/2015 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Department of Pharmacology
Block A: Waterhouse Buildings
1–5 Brownlow Street
Liverpool
L69 3GL
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 01/06/2021 | 21/09/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
21/09/2021: Publication reference added.
24/07/2020: Thesis added.
07/07/2017: Plain English summary added.
