Ignite Creation Date:
2025-12-24 @ 7:59 PM
Ignite Modification Date:
2025-12-25 @ 5:33 PM
Study NCT ID:
NCT03497104
Status:
COMPLETED
Last Update Posted:
2023-11-15
First Post:
2018-04-05
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
The Markers and Paracetamol Poisoning Study 2
Sponsor:
NHS Lothian
Organization:
Study Overview
Official Title:
The Markers and Paracetamol Poisoning Study 2 - Early Diagnosis of Drug-induced Liver Injury Using Point of Care Detection of microRNA
Status:
COMPLETED
Status Verified Date:
2022-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MAPP2
Brief Summary:
Paracetamol overdose is one of the most common medical emergencies. Annually in the UK, 100,000 people seek medical attention and 50,000 need hospital admission. Treatment is with the antidote acetylcysteine (NAC), which is effective but takes 21 hours to administer intravenously and frequently produces adverse reactions.
Current tools that are used to decide who needs treatment are inadequate. this trial team have identified and validated new blood tests that accurately identify those patients at risk of liver injury by quantifying the fundamental in vivo toxicity mechanisms.
This study aim to gain further samples in order to develop a new point-of-care test specifically for the detection of liver damage.
Current tools that are used to decide who needs treatment are inadequate. this trial team have identified and validated new blood tests that accurately identify those patients at risk of liver injury by quantifying the fundamental in vivo toxicity mechanisms.
This study aim to gain further samples in order to develop a new point-of-care test specifically for the detection of liver damage.
Detailed Description:
Paracetamol overdose is one of the most common medical emergencies. Annually in the UK, 100,000 people seek medical attention and 50,000 need hospital admission. Treatment is with the antidote acetylcysteine (NAC), which is effective but takes 21 hours to administer intravenously and frequently produces adverse reactions. Paracetamol is the commonest cause of acute liver failure and directly kills around 200 people/year in the UK. Management of paracetamol overdose is estimated to cost around £48 million/year to the NHS.
Current tools that are used to decide who needs treatment are inadequate. This trial team have identified and validated new blood tests that accurately identify those patients at risk of liver injury by quantifying the fundamental in vivo toxicity mechanisms. Over the last 4 years the team have published data in leading journals such as The Lancet, Lancet Gastroenterology (the MAPP Trial), Hepatology and Clinical Pharmacology \& Therapeutics. The current gold standard marker, serum Alanine Aminotransferase Test (ALT) activity, lacks both sensitivity and specificity for early liver injury. This has resulted in being able to qualify 3 new liver biomarkers in over 1,200 patients (microRNA-122 (miR-122), High Mobility Group Box protein 1 (HMGB1) and keratin-18 (K18)) and demonstrated they predict liver injury at first presentation to hospital with high accuracy at a time when ALT is still normal.
This project develops a new point-of-care (POC) test for circulating microRNA specifically for the detection of liver damage after paracetamol overdose. The team have developed the microRNA biomarker (miR-122) to the point where it has received formal regulatory support from the USA Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The proposed assay has backing from worldwide clinical opinion leaders and pharma partners such as AstraZeneca, GSK and Novartis. The engineering solution for POC microRNA detection is underpinned by robust pilot data and field-leading expertise. The current assay for miR-122 is PCR following extensive sample preparation which is too slow for acute clinical decision making and for dose-escalation decisions. To address this key roadblock (as identified by the FDA) the team will use electrochemical impedance spectroscopy (EIS). the trial team have over 10 years of experience in EIS-based POC test development. Pilot data demonstrate that EIS can detect miR-122 spiked into buffer and distinguish patients with DILI (high miR-122) from healthy subjects (low miR-122).
Current tools that are used to decide who needs treatment are inadequate. This trial team have identified and validated new blood tests that accurately identify those patients at risk of liver injury by quantifying the fundamental in vivo toxicity mechanisms. Over the last 4 years the team have published data in leading journals such as The Lancet, Lancet Gastroenterology (the MAPP Trial), Hepatology and Clinical Pharmacology \& Therapeutics. The current gold standard marker, serum Alanine Aminotransferase Test (ALT) activity, lacks both sensitivity and specificity for early liver injury. This has resulted in being able to qualify 3 new liver biomarkers in over 1,200 patients (microRNA-122 (miR-122), High Mobility Group Box protein 1 (HMGB1) and keratin-18 (K18)) and demonstrated they predict liver injury at first presentation to hospital with high accuracy at a time when ALT is still normal.
This project develops a new point-of-care (POC) test for circulating microRNA specifically for the detection of liver damage after paracetamol overdose. The team have developed the microRNA biomarker (miR-122) to the point where it has received formal regulatory support from the USA Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The proposed assay has backing from worldwide clinical opinion leaders and pharma partners such as AstraZeneca, GSK and Novartis. The engineering solution for POC microRNA detection is underpinned by robust pilot data and field-leading expertise. The current assay for miR-122 is PCR following extensive sample preparation which is too slow for acute clinical decision making and for dose-escalation decisions. To address this key roadblock (as identified by the FDA) the team will use electrochemical impedance spectroscopy (EIS). the trial team have over 10 years of experience in EIS-based POC test development. Pilot data demonstrate that EIS can detect miR-122 spiked into buffer and distinguish patients with DILI (high miR-122) from healthy subjects (low miR-122).
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: