DIAPHRAGM: Diagnostic and prognostic biomarkers in the rational assessment of mesothelioma
| ISRCTN | ISRCTN10079972 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10079972 |
| Secondary identifying numbers | DIAPHRAGM-2013 |
- Submission date
- 03/10/2013
- Registration date
- 17/10/2013
- Last edited
- 20/10/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English Summary
Contact information
Dr Kevin Blyth
Scientific
Scientific
Consultant Respiratory Physician & Honorary Senior
Clinical Lecturer
Department of Respiratory Medicine
Southern General Hospital
1345 Govan Road
Glasgow
G51 4TF
United Kingdom
| Phone | +44 (0)141 232 4026 |
|---|---|
| kevin.blyth@ggc.scot.nhs.uk |
Study information
| Study design | Prospective multi-centre observational study incorporating a nested cross-sectional sub-study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | DIAPHRAGM study: to prospectively assess whether the levels of two novel biomarkers (SOMAscan and Fibulin-3) in blood, can distinguish between malignant pleural mesothelioma (MPM), other malignant pleural effusions and from people who have had previous exposure to asbestos but have no evidence of MPM |
| Study acronym | DIAPHRAGM |
| Study hypothesis | Novel biomarkers are urgently required for the diagnosis, prognostication and monitoring of MPM. An ideal MPM biomarker would be measurable in blood, have sufficient sensitivity and specificity for MPM to improve diagnostic accuracy in patients presenting with a pleural effusion, provide useful prognostic/monitoring information in patients with confirmed MPM and clinicians would have a clear understanding of the biological basis of the information provided. We hypothesise that SOMAscan and/or Fibulin-3 will provide clinically useful diagnostic/prognostic information regarding MPM when these biomarkers are measured in blood, in patients presenting with suspected pleural malignancy. The primary aim is to determine whether levels of SOMAscan and/or Fibulin-3 in blood at presentation can differentiate MPM from asbestos-exposed controls and patients with other causes of pleural effusion with sufficient degree of sensitivity and specificity to be of routine clinical value. Secondary aims are: 1. Determine whether levels of SOMAscan and/or Fibulin-3 at presentation provide clinically useful prognostic information in MPM patients 2. Determine whether early changes in SOMAscan and/or Fibulin-3 levels after diagnosis (defined by a change in levels at 3 months) are associated with a poorer prognosis in MPM. Exploratory Aims: 1. Determine whether there is any correlation between SOMAscan and/or Fibulin-3 levels in blood and tumour volume, defined by contrast-enhanced Magnetic Resonance Imaging 2. Determine whether there is any correlation between SOMAscan and/or Fibulin-3 levels in blood and tumour angiogenesis (defined by redistribution rate constant (Kep) and elimination rate constant (Kel)) on contrast-enhanced magnetic resonance (MR) imaging 3. Determine whether there is any correlation between SOMAscan and/or Fibulin-3 levels in blood and pleural fluid at presentation in patients with MPM 4. Determine whether SOMAscan and/or Fibulin-3 levels are affected by pleural fluid drainage and pleurodesis at the time of diagnosis |
| Ethics approval(s) | West of Scotland REC 1; REC Ref: 13/WS/0240, approval pending |
| Condition | Suspected pleural malignancy or documented history of asbestos exposure |
| Intervention | Patients with suspected pleural malignancy: Visit 1 (Day 0, first clinic visit or in patient stay at hospital) Core Study Activity: 1. Asbestos exposure history 2. Review eligibility criteria 3. Introduce to study if eligibility criteria met 4. Provide with Core Study Patient Information Sheet (at clinic or via post) Visit 2 (Day 3) Core Study Activity: 1. Opportunity for discussion regarding study 2. Sign core study consent form 3. Register patient with Clinical Trials Unit 4. ECOG Performance Status 5. Blood draw for biomarkers with appropriate processing and storage 6. Asbestos exposure history (if not previously performed) 7. Record baseline prognostic indicators, including haemoglobin, leucocyte and platelet counts, lactate dehydrogenase, c-reactive protein and albumin Visit 3 (Day 9) Core Study Activity: 1. If a diagnosis of MPM is made - enter follow-up 2. If any non-MPM diagnosis made - exit study MRI sub-study activity If no diagnosis is made - consider MRI sub-study (only in WOS patients) 1. Review sub-study eligibility criteria 2. Introduce sub-study if eligible 3. Provide with separate sub-study PIS 4. MRI Safety Questionnaire 5. X-ray orbits if any history of eye injury and retained metallic foreign body Visit 3a (Day 11-18) Core Study Activity: None MRI sub-study activity 1. Opportunity for further discussion with CRF 2. MRI Safety Questionnaire (if not previously recorded) 3. Sign sub-study Consent From 4. Register subject with CTU 5. Pleural MRI scan Visit 4 (Day 14-21) Core Study Activity: No activity MRI sub-study activity Paired Blood and Pleural Fluid Draw for biomarkers with appropriate processing and storage Visit 5 (day 23-31) Core Study Activity: 1. If diagnosis of MPM made - enter follow-up 2. If non-MPM diagnosis made - exit study MRI sub-study activity: None Visit 6 (Day 62) Core Study Activity: Blood draw for SOMAscan and Fibulin-3 MRI sub-study activity: None Visit 7 (Day 123) Core Study Activity: Blood draw for SOMAscan and Fibulin-3 MRI sub-study activity: None Follow Up Assessment Core Study Activity: Two monthly follow up assessments to be performed to determine survival status and any cancer treatments delivered |
| Intervention type | Other |
| Primary outcome measure | 1. SOMAscan and Fibulin-3 in blood at presentation 2. Final diagnosis reached |
| Secondary outcome measures | 1. SOMAscan and Fibulin-3 levels at presentation and at 3 months 2. Survival Exploratory Research Outcomes 1. Correlation between SOMAscan and/or Fibulin-3 levels and tumour volume, defined by planimetry at contrast-enhanced Magnetic Resonance Imaging 2. Correlation between SOMAscan and/or Fibulin-3 levels and tumour angiogenesis, Redistribution rate constant (Kep) and elimination rate constant (Kel)) on contrast-enhanced magnetic resonance (MR) imaging 3. SOMAscan and Fibulin-3 in paired blood and pleural fluid samples 4. SOMAscan and Fibulin-3 levels at presentation and at 1 month post-biopsy and pleurodesis |
| Overall study start date | 01/11/2013 |
| Overall study end date | 31/10/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 709 in total: 600 participants with Suspected Pleural Malignancy and 109 participants with asbestos expsure |
| Participant inclusion criteria | Cases of suspected pleural malignancy: 1. Informed written consent 2. Suspected pleural malignancy, as defined by a unilateral pleural effusion or pleural-based mass lesion 3. Sufficient fitness for diagnostic sampling, including diagnostic pleural aspiration as a minimum 4. Aged over 18 Patients with suspected pleural malignancy recruited to the cross-sectional sub-study will be subject to the following additional inclusion criteria: 1. Recruited in a WoS centre (Southern General, Gartnavel General, Glasgow Royal) 2. Thoracoscopy indicated to investigate suspected pleural malignancy (defined by negative pleural cytology and non-specific CT findings) 3. Aged over 18 Asbestos-exposed subjects: 1. Documented history of asbestos exposure and associated pleural plaques, asbestosis or diffuse pleural thickening 2. Informed written consent 3. Willing and able to travel to a research clinic interview in Glasgow 4. Aged over 18 |
| Participant exclusion criteria | Cases of suspected pleural malignancy: 1. Insufficient fitness (based on the site investigators clinical judgement) for diagnostic sampling, including diagnostic pleural aspiration as a minimum Patients with suspected Pleural Malignancy recruited to the cross-sectional sub-study will be subject to the following additional exclusion criteria: 1. Claustrophobia 2. Pregnancy 3. Unable to undergo MR imaging due to known contraindications (e.g. pacemaker, ferrous metal implants or foreign body) 4. Allergy to Gadolinium contrast 5. Renal impairment (eGFR <30ml/min) Asbestos-exposed subjects: 1. Known MPM 2. Known pleural effusion of any cause |
| Recruitment start date | 01/11/2013 |
| Recruitment end date | 31/10/2016 |
Locations
Countries of recruitment
- Ireland
- Scotland
- United Kingdom
Study participating centre
Southern General Hospital
Glasgow
G51 4TF
United Kingdom
G51 4TF
United Kingdom
Sponsor information
NHS Greater Glasgow and Clyde (UK)
Hospital/treatment centre
Hospital/treatment centre
c/o Dr Nathaniel Brittain
Research and Development Central Office
The Tennent Institute, 1st Floor
Western Infirmary
38 Church Street
Glasgow
G11 6NT
Scotland
United Kingdom
| Website | http://www.nhsggc.org.uk/r&d |
|---|---|
"ROR" |
https://ror.org/05kdz4d87 |
Funders
Funder type
Government
Chief Scientist Office (UK) Ref: ETM/285
Government organisation / Local government
Government organisation / Local government
- Alternative name(s)
- CSO
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 24/11/2016 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
20/10/2017: Publication reference added.
