Condition category
Infections and Infestations
Date applied
29/05/2020
Date assigned
22/06/2020
Last edited
22/06/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

DIAMONDS – Diagnosis and Management of Febrile Illness using RNA Personalised Molecular Signature Diagnosis – is a five-year collaborative, multi-partnered research project that will develop a new molecular diagnostic test to provide rapid diagnosis of common infectious bacterial disease, as well as viral and inflammatory diseases. It involves an international, multi-disciplinary team of researchers and scientists from across 28 institutions and 13 countries with 11 of those countries from Europe.
The DIAMONDS research team is addressing the problem that clinicians have when patients who have common symptoms (such as fever) come to hospital. Common infectious and inflammatory diseases account for up to a third of all unplanned hospital and primary care attendances. Currently, if a patient is admitted to hospital with a fever and non-specific symptoms, they could go through a whole series of investigations, such as blood tests, spinal fluid samples, MRI and CT scans, to help clinicians try to identify the cause of their symptoms. These tests can be uncomfortable, expensive and a patient could be waiting days or even weeks before they receive an accurate diagnosis and appropriate treatment, for example patients are often treated with antibiotics as a precautionary measure against serious bacterial infections, which have no effect if the real diagnosis is a self-resolving viral infection. All this puts a huge strain on the patient and the healthcare system.
When trying to find a solution to this problem, researchers have previously found that common diseases are characterised by unique patterns of gene expression (the process of DNA information being converted into instructions for cells to make proteins and other molecules). When a disease is associated with the switching on and off of genes in a patient’s blood, it forms its own ‘gene signature’. The gene signature has previously been shown to identify bacterial infections with a 95-100% accuracy.
The DIAMONDS research team will use expertise from previous gene signature research to make diagnosis faster and more accurate. The aim is to shorten the diagnosis time to under two hours, using a patient’s first blood sample. This diagnostic test may save a patient from unnecessary and potentially painful tests, as well as revolutionise the way healthcare can be delivered and have a positive impact on the health system and medical practitioners delivering healthcare.
The first part of the project is recruitment patients with conditions caused by infection and inflammation into DIAMONDS Search. Samples will be taken during the episodes of acute and convalescent illness. Selected optimal gene signatures for a wide range of infections and inflammatory conditions will be used to build a data library of the identifiable gene signatures of common inflammatory and infectious diseases. By comparing the pattern of genes in a patient’s blood sample to the hundreds of gene signatures in the library, diagnosis can be made rapidly.
Gene signatures selected from the data library will be used on both existing devices and new prototypes, such as lab-on-chip technology to create test devices, to enable diagnosis of multiple conditions on the same device - a concept called Personalised Molecular Signature Diagnosis (PMSD). PMSD-based care could transform the management of suspected infectious or inflammatory diseases, by driving more efficient and equitable organisation of the way care is delivered to the large numbers of patients presenting with symptoms of infection or inflammation.
As part of the global response to the coronavirus pandemic, the DIAMONDS consortium has re-purposed DIAMONDS Search to tackle the urgent global need for improved diagnostics to guide clinical management of patients with confirmed or suspected SARS-CoV-2. The DIAMONDS consortia is undertaking rapid development of novel host RNA-based diagnostic devices that can diagnose SARS-CoV-2 infection and comparator illnesses simultaneously at the point of testing and also to discriminate pure SARS-CoV-2 infection from that caused by co-infections, for instance with bacteria or other infections. DIAMONDS will also elucidate host gene expression signatures associated with different manifestations of Covid-19, inflammatory disease and uncontrolled viral disease.

DIAMONDS is recruiting patients of all ages with suspected and proven Covid-19, across the full spectrum of disease from mild (not admitted to hospital), moderate (admitted to ward only) and severe (intensive care). Samples and data from these highly characterised patients will be used by DIAMONDS consortium biotechnology partners to develop devices to detect diagnostic RNA signature of SARS-CoV-2 infection and signatures predictive of severe disease.

We will not be analysing the clinical information or samples while the patient is in hospital, but will be storing them to be analysed later, so the results are not likely to help manage the patient's illness and will not affect the patient's clinical care. However, the information gained by the study may help improve the diagnosis and treatment patients in the future.If we find significant results that would influence the patient's future care, the clinical care team will contact the patient.There are no disadvantages to joining the study. The small additional amount of blood and other samples taken should not make a difference to the patient's well-being.

DIAMONDS has research funding, totalling €22.5 million over five years, which is provided by the European Commission under the Horizon 2020 research and innovation programme.

Unfortunately, this study is not recruiting public volunteers at this time. This is because researchers are directly identifying volunteers in certain hospitals. Please do not contact the research team as they will not be able to respond. For more information about COVID-19 research, visit the Be Part of Research homepage.

Trial website

https://www.diamonds2020.eu

Contact information

Type

Scientific

Primary contact

Prof Michael Levin

ORCID ID

http://orcid.org/0000-0003-2767-6919

Contact details

Dept of Paediatrics
Medical School Building
Imperial College London
Norfolk Place
Paddington
London
W2 1PG
United Kingdom
+44 (0)207 594 3990
m.levin@imperial.ac.uk

Type

Public

Additional contact

Dr Federico Martinón-Torres

ORCID ID

http://orcid.org/0000-0002-9023-581X

Contact details

Pediatría Clínica
Infectológica y Traslacional
Hospital Clínico Universitario de Santiago de Compostela
A Choupana
15706 Santiago de Compostela
15706
Spain
+34 (0)981 955373
Federico.Martinon.Torres@sergas.es

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

20SM5903, IRAS 278651, CPMS 45537

Study information

Scientific title

Diagnosis and management of febrile illness using RNA personalised molecular signature diagnosis

Acronym

DIAMONDS

Study hypothesis

The aim of DIAMONDS is to design new diagnostic tests that can tell quickly and accurately what illness a patient has when they come to hospital with common symptoms such as fever. This would help the right treatment to be given to the right patient, at the right time (‘personalised medicine’).

There are two recruitment studies in DIAMONDS; DIAMONDS Search which will recruit patients and controls for the first 3 years of the study and DIAMONDS Pilot Demonstration study which will subsequently recruit patients and controls for one year.

Patients with suspected infectious disease or inflammatory disease will be recruited into DIAMONDS Search. Samples will be taken during the acute illness and convalescence, RNA will be extracted from blood samples and the optimum RNA signatures (gene transcripts) for each infectious and inflammatory condition will be selected.

The selected RNA signatures will be used to develop a European Diagnostic Transcriptomic Library (EDTL) whose molecular taxonomy of infectious and inflammatory disease will be used as the basis for personalised diagnosis (“Personalised Molecular Signature Diagnosis (PMSD)”). RNA signatures from EDTL will be used to develop a diagnostic test device which can be used to diagnose infectious and inflammatory conditions. The performance of PMSD will be evaluated by recruitment of patients with infectious disease or inflammatory disease and controls study into the DIAMONDS Pilot Demonstration study.

The COVID-19 pandemic has presented the opportunity to undertake rapid development of a host blood host RNA test to distinguish SARS-CoV-2 Infection from other viral and bacterial infection.

Hypothesis:
The underlying diagnosis in patients presenting with illness suggestive of infection or inflammation can be accurately discriminated using tests that interrogate the gene expression levels of a modest number of transcripts in whole blood.

Ethics approval

Approved 14/04/2020, London - Dulwich Research Ethics Committee (Health Research Authority, Skipton House, 80 London Road, London, SE1 6LH, UK; +44 (0)207 104 8241; dulwich.rec@hra.nhs.uk), ref: 20/HRA/1714

Study design

Observational case-control laboratory study

Primary study design

Observational

Secondary study design

Case-control study

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Patients with suspected infection or suspected inflammatory conditions including patients with suspected COVID-19 (SARS-CoV-2 infection)

Intervention

The researchers will use case-controlled groups of patients presenting to hospital, recruited across Europe, The Gambia and Asia to discover biomarkers of infectious and inflammatory disease, using multi-omic analysis of blood samples from already-available, and prospectively recruited patient samples, from patients with clearly defined clinical conditions, comprising the discovery group. After establishing the gene expression profiles for different conditions, they will validate these on a second, validation group of patients, including prospectively recruited patients in DIAMONDS Search, and samples from other similar ethically approved studies. They will establish a molecular taxonomy of infectious and inflammatory disease and will develop and configure diagnostic devices to rapidly detect gene transcripts required for Personalised Molecular Signature Diagnosis (PMSD).

Intervention type

Genetic

Phase

Drug names

Primary outcome measure

Gene expression measured using RNA sequencing at presentation in children and adults with different infectious and inflammatory conditions

RNA biomarker signature with a sensitivity of 95% and specificity of 95% based on groups of at least 50 patients in each diagnostic category, which would allow capture of the effect sizes between the different comparator groups of as little as 1.5 fold change.

Secondary outcome measures

Healthcare resource use of patients presenting with infectious and inflammatory illness measured using qualitative questionnaire during admission and 3-6 months after admission

Overall trial start date

01/01/2020

Overall trial end date

30/05/2025

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. A patient of any age who attends or who is admitted at a participating hospital
2. AND who has one or more of the following;
2.1. Fever (≥38.0 °C) or history of fever in the preceding 24 hours
2.2. Symptoms (including non-specific signs) suggestive of infection
2.3. Symptoms suggestive of inflammation (including exacerbation of pre-existing inflammatory disease), and including non-specific signs/symptoms such as fever, joint pains, muscle pains, headaches, lymphadenopathy/fatigue, abdominal pain, rashes, mucosal inflammation, elevated inflammatory markers, unexplained cytopenias
3. AND EITHER who gives consent for samples to be taken for research
4. OR who retrospectively gives consent, according to a deferred consent model in which consent is obtained after initial sample collection

Participant type

Patient

Age group

All

Gender

Both

Target number of participants

5000

Participant exclusion criteria

1. Patients who do not give consent
2. RNA sample is not taken

Recruitment start date

27/04/2020

Recruitment end date

30/05/2023

Locations

Countries of recruitment

Austria, France, Gambia, Germany, Greece, Italy, Latvia, Nepal, Netherlands, Slovenia, Spain, Switzerland, Taiwan, United Kingdom

Trial participating centre

Imperial College London
Dept of Paediatrics Norfolk Place Paddington
London
W2 1PG
United Kingdom

Trial participating centre

Imperial College NHS Healthcare Trust
St Mary's Hospital, Paddington
London
W2 1NY
United Kingdom

Trial participating centre

London School of Hygiene and Tropical Medicine
Keppel St Bloomsbury
London
WC1E 7HT
United Kingdom

Trial participating centre

University of Oxford
John Radcliffe Hospital Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Liverpool University
Alder Hey Children's Hospital Eaton Road
Liverpool
L12 2AP
United Kingdom

Trial participating centre

University of Newcastle
Royal Victoria Infirmary New Victoria Wing Queen Victoria Road
Newcastle Upon Tyne
NE1 4LP
United Kingdom

Trial participating centre

Aintree University Hospital
Lower Lane Fazakerley
Liverpool
L9 7AL
United Kingdom

Trial participating centre

Evelina London Children's Hospital
Westminster Bridge Rd
London
SE1 7EH
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Royal Alexandra Children's Hospital
North Drive
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Academisch Medisch Centrum, Universiteit van Amsterdam
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

Trial participating centre

Erasmus University Medical Center
Doctor Molewaterplein 40
Rotterdam
3015 GD
Netherlands

Trial participating centre

Stichting Katholieke Universiteit, Radboud University
Geert Grooteplein Zuid 10
Nijmegen
6525 GA
Netherlands

Trial participating centre

UMC Utrecht
Heidelberglaan 100
Utrecht
3584 CX
Netherlands

Trial participating centre

Ludwig Maximilians University (LMU)
Div. Paediatric Infectious Diseases Hauner Children’s Hospital University Hospital, Ludwig Maximilians University (LMU) Medical Center of the University of Munich Ziemssenstraße 1
München
80336
Germany

Trial participating centre

Assistance Publique - Hopitaux De Paris
3 Avenue Victori
Paris
75004
France

Trial participating centre

Universita Degli Studi di Milano
Via Festa del Perdono 7
Milan
20122
Italy

Trial participating centre

Bambino Gesù Hospital
Piazza di Sant'Onofrio, 4
Rome
00165
Italy

Trial participating centre

Servicio Galego de Saúde
Hospital Clínico Universitario de Santiago de Compostela A Choupana
Santiago de Compostela
15706
Spain

Trial participating centre

Fundacion Para La Investigacion Biomedica Del Hospital Universitario "Doce De Octubre
Plaza de Carlos Trias Bertrán
Madrid
28020
Spain

Trial participating centre

National and Kapodistrian University Of Athens
National and Kapodistrian University of Athens (NKUA) School of Medicine P. and A. Kyriakou Children’s Hospital
Athens
115 27 Athens
Greece

Trial participating centre

Rīgas Stradiņa Universitāte
Dzirciema iela 16 Kurzemes rajons
Riga
LV-1007
Latvia

Trial participating centre

Univerzitetni Klinični Center, Ljubljana
University Children’s Hospital University Medical Centre Ljubljana Bohoričeva 20
Ljubljana
SI-1000 Ljubljana
Slovenia

Trial participating centre

Inselspital, Bern University Hospital
Department of Pediatrics Inselspital, Bern University Hospital University of Bern Freiburgstrasse 18
Bern
3010
Switzerland

Trial participating centre

National Cheng Kung University Hospital
No. 138號, Shengli Road North District
Tainan City
704
Taiwan

Trial participating centre

MRC Unit The Gambia at LSHTM
Atlantic Boulevard P. O. Box 273
Fajara
-
Gambia

Trial participating centre

Patan Academy of Health Sciences Pediatric Research
Kathmandu
-
Nepal

Trial participating centre

Medical University Graz
Department of General Paediatrics
Graz
-
Austria

Sponsor information

Organisation

Imperial College London

Sponsor details

2nd Floor
Medical School Building
Norfolk Place
Paddington
London
W2 1PG
United Kingdom
+44 (0)207 594 9480
k.boland@imperial.ac.uk

Sponsor type

University/education

Website

http://www3.imperial.ac.uk/

Funders

Funder type

Government

Funder name

European Commission

Alternative name(s)

EC

Funding Body Type

unknown

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal around one year after the overall end of the study. No additional files available.

IPD sharing statement
The datasets generated during and/or analysed during the current study will be stored in a publically available repository.

Intention to publish date

30/05/2026

Participant level data

Stored in repository

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

29/05/2020: Trial's existence confirmed by the NIHR.