Trial Information

Status:

Open

Specialty:

All

Date Opened:

19/10/2023

Planned Close date:

30/04/2028

Sponsors:

Newham University Hospital NHS Trust,University of Liverpool

Site Recruitment:

5 /

5

Principal Investigator:

Dr Sarah Moon

Study Title:

Molecular Genetics of Adverse Drug Reactions (MOLGEN)

Contacts

Research Nurse / Study Coordinator:

Hilary Thatcher

Administrator:

-

Molecular genetics of adverse drug reactions: from candidate genes to genome wide association studies

Adverse drug reactions (ADR's) are a common cause of drug-related morbidity and may account for about 6.5% of all hospital admissions. A meta-analysis of studies performed in the USA has shown that ADRs may be the fourth commonest cause of death. ADRs are also a significant impediment to drug development, and a significant cause of drug withdrawal. The purpose of this research is to (a) identify patients with different types of adverse drug reactions; (b) using DNA obtained from blood or Saliva samples from these patients, identify genetic factors which predispose to adverse reactions. The net effect of our research will be the development of genetic tests which can help in predicting individual susceptibility to adverse reactions prior to the medication's administration. Patients with a pre-disposition to reacting adversely can be prescribed alternative medication of monitored more closely during their treatment. This will reduce the harm for patients and save valuable resources for the NHS. We aim to recruit 250 cases for each reaction for a period of eight years throughout multiple sites in the UK. Specific adverse drug reactions we are looking at include: - Statin induced myotoxicity, characterised by high CK - Severe hypersensitivity reactions including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis - Anaphylaxis induced by NMBA anaesthetics - ACE inhibitor or ARB induced angioedema - Taxane hypersensitivity - Chemotherapy induced peripheral neuropathy - Bleomycin induced lung toxicity - Clozipine induced agranulocytosis or neutropenia - Bisphosphonate-related osteonecrosis of the jaw - Tenofovir associated renal injury - Serious bleeds induced by warfarin or other anticoagulants Arms for Dihydropyrimidine Dehydrogenase (DPYD) Glaucoma Anthracycline of Induced Cardiotoxicity (ACT) are now open on the study.

> Patient willing to take part < br / >> 18 years of age or over < br / >> Diagnosed with Adverse Drug Reaction (ADR). < br / > < br / >ADR’s can affect almost any organ system: for the purpose of this project, the patients to be recruited in general will have had one or more of these reactions: < br / > < br / > (A) Generalised hypersensitivity reactions (characterised by fever, skin rash and eosinophilia); < br / > < br / > (B) Skin reactions which required drug discontinuation; < br / > < br / > (C) Hepatotoxicity; < br / > < br / > (D) Haematological toxicity including agranulocytosis and aplastic anaemia; < br / > < br / > (E) Pneumonitis; < br / > < br / > (F) Metabolic abnormalities such as lipodystrophy and insulin resistance < br / > < br / > (G) Retinal problems including retinopathy and visual field constriction. < br / > < br / > (H) Bleeding from anticoagulants < br / > < br / > (I) Muscle toxicity associated with drugs such as statins < br / > < br / > (J) Renal toxicity (including interstitial nephritis, tubular dysfunction, acute renal failure) < br / > < br / > (K) Extrapyramidal reactions from antipsychotics < br / > < br / > (L) Depression caused by drugs such as isotretinoin. < br / > < br / > (M) Osteonecrosis of the jaw associated with bisphosphonates. < br / > < br / > (N) Anaphylaxis to anaesthetics < br / > < br / > (O)Anaphylaxis to chemotherapy < br / > < br / > (P)Chemotherapy induced peripheral neuropathy < br / > < br / > (Q) Lung toxicity associated with bleomycin < br / > < br / > (R) Hodgkins lymphoma associated with bleomycin < br / > < br / > (S) Angiotensin-convertin enzyme (ACE) inhibitor induced angioedema < br / > < br / > > Written informed consent obtained < br / > > If patient lacks capacity to consent then a personal consultee or a nominated consultee will be approached (Only applies to NHS sites in England, which are set up for this process)

> Patient unwilling to take part < br / > > Patient is, in the opinion of the Investigator, not suitable to participate in the study. < br / > > Unable to obtain written informed consent < br / > > Unable to nominate a consultee for patients who lack capacity (Only applies to NHS sites in England, which are set up for this process)