Plain English Summary
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
Trial website
Additional identifiers
EudraCT number
2013-002743-28
ClinicalTrials.gov number
Protocol/serial number
15543
Study information
Scientific title
A pharmacokinetic investigation into the formation of carbamazepine metabolites and carbamazepine-protein conjugates in epilepsy patients
Acronym
PICME II
Study hypothesis
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
13/NW/0503
Study design
Non-randomised; Both; Treatment
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a patient information sheet
Condition
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 names
Carbamazepine
Primary outcome measure
Pharmacokinetic analyses; Timepoint(s): Time points dependent on time of presentation to clinic
Secondary outcome measures
N/A
Overall trial start date
05/11/2013
Overall trial end date
30/04/2015
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 158; UK Sample Size: 158
Participant 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
Recruitment start date
05/11/2013
Recruitment end date
30/04/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University of Liverpool
Wolfson Centre for Personalised Medicine
Department of Pharmacology
Block A: Waterhouse Buildings
1–5 Brownlow Street
Liverpool
L69 3GL
United Kingdom
Funders
Funder type
Government
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
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list