Condition category
Nervous System Diseases
Date applied
18/02/2015
Date assigned
19/02/2015
Last edited
07/07/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

Contact information

Type

Scientific

Primary contact

Dr Vincent Yip

ORCID ID

Contact details

University of Liverpool
Wolfson Centre for Personalised Medicine
Department of Pharmacology
Block A: Waterhouse Buildings
1–5 Brownlow Street
Liverpool
L69 3GL
United Kingdom

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 measures

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

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

Sponsor information

Organisation

University of Liverpool

Sponsor details

Head of Division of Primary Care
Whelan Building
Quadrangle
Brownlow Hill
Liverpool
L69 3GB
United Kingdom

Sponsor type

University/education

Website

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

07/07/2017: Plain English summary added.