Prostate CancerCLIMATENCT05020522
Comparison of Diagnostic Accuracy of Luminal Index and MP MRI for Accelerated deTEction of Significant Prostate Cancer
A study testing Luminal Index MRI (LI-MRI), LI-MRI targeted prostate biopsy and Plasma methylation signature (ctMethSig) in people with Prostate Cancer, run by University College, London at 1 site in United Kingdom.
Trial summary
Multi-parametric (mp) MRI has now internationally been incorporated as standard of care in the work-up of participants with suspected prostate cancer. The standard mpMRI protocol requires 30-45 minutes to be performed and has a sensitivity and specificity of approximately 90% and 50% for the detection of clinically… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Luminal Index MRI (LI-MRI), LI-MRI targeted prostate biopsy and Plasma methylation signature (ctMethSig)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 702 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 May 2022to 1 Mar 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men with clinically suspected prostate cancer and referred for prostate MRI
- Willing and able to provide a written informed consent
Who cannot join
- Prostate specific antigen (PSA) level > 20ng/ml within 6 months
- Previous diagnosis of prostate cancer
- Ongoing hormone treatment within 3 months prior to MRI, excluding antiandrogens or 5-alpha reductase inhibitors
- Contraindication to MRI scan
- Contraindication to administration of gadolinium-based contrast agents
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
University College London Hospitals NHS Foundation Trust
London
Shonit Punwani
About this study
Official title: A Comparison of the Diagnostic Accuracy of Luminal Index Magnetic Resonance Imaging and Multi-parametric Magnetic Resonance Imaging for the Accelerated Detection of Significant Prostate Cancer
Multi-parametric (mp) MRI has now internationally been incorporated as standard of care in the work-up of participants with suspected prostate cancer. The standard mpMRI protocol requires 30-45 minutes to be performed and has a sensitivity and specificity of approximately 90% and 50% for the detection of clinically significant prostate cancer. Compared to the non-targeted systematic transrectal ultrasound (TRUS) biopsy approach in men with clinically suspected prostate cancer (e.g.: elevated PSA), performing mpMRI as a triage test allows to detect clinically significant cancer in more men (38% vs 26%) and clinically insignificant cancer in less men (9% vs 22%), while avoiding biopsy in roughly one third of men.
However, there is need for improvement in the prostate diagnostic pathway even after incorporation of mp-MRI, specifically mpMRI can miss significant cancer in around 10% of cases and only 50% of positive scans turn out to harbor significant cancer at biopsy. Moreover, the key functional imaging sequence of mp-MRI (i.e.: DWI) often suffers from image artifacts causing difficulty in scan interpretation.
Read more
To address these issues the investigators aim to investigate Luminal Index MRI (LI-MRI), a novel method of MR imaging that requires only up to 10 minutes to be performed and doesn't require the use of contrast media. LI-MRI has shown promising results for the characterization of prostate cancer.
In this study the diagnostic performance of LI-MRI and mpMRI for the detection of prostate cancer will be directly compared.
Read the detailed description
Luminal Index MRI (LI-MRI). LI-MRI is a novel technique that allows the assessment of luminal water fraction (LWF). The normal prostate consists of a glandular lumen and cellular areas; cancer alters the balance of glandular to cellular spaces, reducing the fraction of glandular lumen. This fraction decreases further as the grade of tumor increases. Using a multiecho T2-weighted sequence, investigators can differentiate between long T2 values of the luminal space and the short T2 values of the stromal/epithelial space. The luminal index of an image pixel can be calculated as a fraction of the area of the luminal space to the sum of cellular-stromal and luminal space. Studies have shown a good correlation between LWF and its histological measurement, with potential to detect prostate cancer and predict tumor grade. From the results of preliminary studies, the optimized LI-MRI sequence has been very good at differentiating clinically significant and non-significant tumors.
PURPOSE. The purpose of the study is to compare the diagnostic performance of LI-MRI (up to 10 minutes scan, no contrast required) and mp-MRI (35-40 min scan, intravenous contrast injection required) for the detection of clinically significant prostate cancer.
DESIGN. This is a prospective, multi-centre, paired, non-randomised, comparative study. Patients with clinically suspected prostate cancer that are scheduled for mpMRI as part of their routine diagnostic workup will be asked to participate to the study. All participants will undergo an additional LI-MRI sequence during the clinical scan session. Mp-MRI and LI-MRI images will be interpreted independently by different radiologists, blinded to the results of the other test. Targeted biopsies will be performed for any suspicious lesion (i.e. MRI score 3-4-5) detected with mpMRI and/or LI-MRI, blinded to the source of the lesion. The diagnostic performance of the two techniques will then be assessed using the results of the targeted biopsy.
An optional translational study will also be performed to investigate the ability of DNA methylation signatures in the plasma to identify men at high risk of metastases from high risk prostate cancer.
- Conditions
- Prostate Cancer
- Being tested
- Luminal Index MRI (LI-MRI), LI-MRI targeted prostate biopsy, Plasma methylation signature (ctMethSig)
- Keywords
- Magnetic Resonance Imaging, Luminal Index MRI, Methylation Signature, Prostate Cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Luminal Index MRI (LI-MRI)Diagnostic test
Multiecho T2 sequence; eventual biopsy of lesion(s) detected with LI-MRI only.
LI-MRI targeted prostate biopsyDiagnostic test
Biopsy targeted to suspicious lesions detected with LI-MRI only
Plasma methylation signature (ctMethSig)Diagnostic test
Blood sample.
| Study group | Role | What they receive |
|---|---|---|
| MRI scan | Other | Mp-MRI, LI-MRI, plasma DNA methylation signature (optional) Receives: Diagnostic Test: Luminal Index MRI (LI-MRI); Diagnostic Test: LI-MRI targeted prostate biopsy; Diagnostic Test: Plasma methylation signature (ctMethSig) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic accuracy of mp-MRI and LI-MRI
Comparison of per-participant diagnostic accuracy of mp-MRI and LI-MRI for the detection of clinically significant prostate cancer (i.e. Gleason 3+4 or higher). Two endpoints are included in the primary outcome: difference in sensitivity and difference in specificity.
Measured: 3 years
Secondary outcomes (10)
Diagnostic accuracy of LI-MRI as an add-on test
Per-participant diagnostic accuracy of LI-MRI as an add-on test in combination with mp-MRI for the detection of clinically significant cancer.
Measured: 3 years
Proportion of correct clinical recommendation
Comparison of the proportion of men who would receive a correct clinical recommendation that biopsy could be avoided using mp-MRI and LI-MRI by retrospective analysis.
Measured: 3 years
Per-lesion diagnostic accuracy of mp-MRI and LI-MRI
Comparison of per-lesion diagnostic accuracy of LI-MRI and mp-MRI for clinically significant cancer (difference in sensitivity and specificity).
Measured: 3 years
Proportion of non-significant cancer detection
Comparison of the proportion of men diagnosed with non-significant cancer (Gleason 3+3) based on LI-MRI and mp-MRI targeted biopsies.
Measured: 3 years
Value of MRI in diagnostic models
Evaluation of the added value of MRI when included in a diagnostic model of clinically significant cancer based on the clinical features of age and PSA density.
Measured: 3 years
Luminal Index quantitative analysis
Correlation between Luminal Index quantitative metric and tumor Gleason grade
Measured: 3 years
Interobserver agreement on LI-MRI scores
Interobserver agreement among radiologists on LI-MRI scores.
Measured: 3 years
Interobserver agreement on Gleason scores
Interobserver agreement among histopathologists on Gleason scores at biopsy.
Measured: 3 years
ctMethSig true positive rate
Proportion of men with clinically significant cancer who are positive with ctMethSig.
Measured: 3 years
ctMethSig false positive rate
Proportion of men without clinically significant cancer who are positive with ctMethSig.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2021
- Study start1 May 2022
- Primary completion1 Mar 2024 (estimated)
- Study completion1 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Paired, non-randomised, comparative study
- Masking
- None (open label)
- Enrolment
- 702 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shonit Punwani, Principal investigator, University College, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05020522
- Sponsor's protocol ID
- 281621
- Acronym
- CLIMATE
- Status last verified
- Oct 2023
- First submitted
- 12 Jul 2021
- Last updated
- 3 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Al-Hammouri T, Brembilla G, Brizmohun M, Tuazon J, Clemente J, Mathew M, Potyka I, Brew-Graves C, Markus J, Giganti F, Parry T, Haider A, Mallett S, Dudderidge T, Barrett T, Attard G, Moore C, Punwani S; CLIMATE Trial Management Group. The 'Comparison of diagnostic accuracy of Luminal Index and standard of care MRI for Accelerated deTEction of prostate cancer' (CLIMATE) trial protocol. BJU Int. 2026 Apr;137(4):611-618. doi: 10.1111/bju.70108. Epub 2026 Jan 25.
PubMed 41582606
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparison of the Diagnostic Accuracy of Luminal Index Magnetic Resonance Imaging and Multi-parametric Magnetic Resonance Imaging for the Accelerated Detection of Significant Prostate Cancer
- ClinicalTrials.gov ID
- NCT05020522
- Acronym / sponsor ID
- CLIMATE / 281621
- Conditions
- Prostate Cancer
- Keywords
- Magnetic Resonance Imaging, Luminal Index MRI, Methylation Signature, Prostate Cancer
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 702 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- 1 May 2022 (actual)
- Primary completion
- 1 Mar 2024 (estimated)
- Study completion
- 1 Mar 2025 (estimated)
- First posted
- 25 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multi-parametric (mp) MRI has now internationally been incorporated as standard of care in the work-up of participants with suspected prostate cancer. The standard mpMRI protocol requires 30-45 minutes to be performed and has a sensitivity and specificity of approximately 90% and 50% for the detection of clinically significant prostate cancer. Compared to the non-targeted systematic transrectal ultrasound (TRUS) biopsy approach in men with clinically suspected prostate cancer (e.g.: elevated PSA), performing mpMRI as a triage test allows to detect clinically significant cancer in more men (38% vs 26%) and clinically insignificant cancer in less men (9% vs 22%), while avoiding biopsy in roughly one third of men.
However, there is need for improvement in the prostate diagnostic pathway even after incorporation of mp-MRI, specifically mpMRI can miss significant cancer in around 10% of cases and only 50% of positive scans turn out to harbor significant cancer at biopsy. Moreover, the key functional imaging sequence of mp-MRI (i.e.: DWI) often suffers from image artifacts causing difficulty in scan interpretation.
To address these issues the investigators aim to investigate Luminal Index MRI (LI-MRI), a novel method of MR imaging that requires only up to 10 minutes to be performed and doesn't require the use of contrast media. LI-MRI has shown promising results for the characterization of prostate cancer.
In this study the diagnostic performance of LI-MRI and mpMRI for the detection of prostate cancer will be directly compared.
Detailed description
Luminal Index MRI (LI-MRI). LI-MRI is a novel technique that allows the assessment of luminal water fraction (LWF). The normal prostate consists of a glandular lumen and cellular areas; cancer alters the balance of glandular to cellular spaces, reducing the fraction of glandular lumen. This fraction decreases further as the grade of tumor increases. Using a multiecho T2-weighted sequence, investigators can differentiate between long T2 values of the luminal space and the short T2 values of the stromal/epithelial space. The luminal index of an image pixel can be calculated as a fraction of the area of the luminal space to the sum of cellular-stromal and luminal space. Studies have shown a good correlation between LWF and its histological measurement, with potential to detect prostate cancer and predict tumor grade. From the results of preliminary studies, the optimized LI-MRI sequence has been very good at differentiating clinically significant and non-significant tumors.
PURPOSE. The purpose of the study is to compare the diagnostic performance of LI-MRI (up to 10 minutes scan, no contrast required) and mp-MRI (35-40 min scan, intravenous contrast injection required) for the detection of clinically significant prostate cancer.
DESIGN. This is a prospective, multi-centre, paired, non-randomised, comparative study. Patients with clinically suspected prostate cancer that are scheduled for mpMRI as part of their routine diagnostic workup will be asked to participate to the study. All participants will undergo an additional LI-MRI sequence during the clinical scan session. Mp-MRI and LI-MRI images will be interpreted independently by different radiologists, blinded to the results of the other test. Targeted biopsies will be performed for any suspicious lesion (i.e. MRI score 3-4-5) detected with mpMRI and/or LI-MRI, blinded to the source of the lesion. The diagnostic performance of the two techniques will then be assessed using the results of the targeted biopsy.
An optional translational study will also be performed to investigate the ability of DNA methylation signatures in the plasma to identify men at high risk of metastases from high risk prostate cancer.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Paired, non-randomised, comparative study
| Arm | Type | Receives |
|---|---|---|
| MRI scan | Other | Diagnostic Test: Luminal Index MRI (LI-MRI), Diagnostic Test: LI-MRI targeted prostate biopsy, Diagnostic Test: Plasma methylation signature (ctMethSig)Mp-MRI, LI-MRI, plasma DNA methylation signature (optional) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Men with clinically suspected prostate cancer and referred for prostate MRI
- Willing and able to provide a written informed consent
Key exclusion criteria (5 listed)
- Prostate specific antigen (PSA) level > 20ng/ml within 6 months
- Previous diagnosis of prostate cancer
- Ongoing hormone treatment within 3 months prior to MRI, excluding antiandrogens or 5-alpha reductase inhibitors
- Contraindication to MRI scan
- Contraindication to administration of gadolinium-based contrast agents
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Luminal Index MRI (LI-MRI)Multiecho T2 sequence; eventual biopsy of lesion(s) detected with LI-MRI only. | Diagnostic test | MRI scan |
| LI-MRI targeted prostate biopsyBiopsy targeted to suspicious lesions detected with LI-MRI only | Diagnostic test | MRI scan |
| Plasma methylation signature (ctMethSig)Blood sample. | Diagnostic test | MRI scan |
Primary outcome
Diagnostic accuracy of mp-MRI and LI-MRI
Time frame: 3 years
Comparison of per-participant diagnostic accuracy of mp-MRI and LI-MRI for the detection of clinically significant prostate cancer (i.e. Gleason 3+4 or higher). Two endpoints are included in the primary outcome: difference in sensitivity and difference in specificity.
10 secondary outcomes
Diagnostic accuracy of LI-MRI as an add-on test
Time frame: 3 years
Proportion of correct clinical recommendation
Time frame: 3 years
Per-lesion diagnostic accuracy of mp-MRI and LI-MRI
Time frame: 3 years
Proportion of non-significant cancer detection
Time frame: 3 years
Value of MRI in diagnostic models
Time frame: 3 years
Luminal Index quantitative analysis
Time frame: 3 years
Interobserver agreement on LI-MRI scores
Time frame: 3 years
Interobserver agreement on Gleason scores
Time frame: 3 years
ctMethSig true positive rate
Time frame: 3 years
ctMethSig false positive rate
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2023.
- Derived from this study: PubMed 41582606Al-Hammouri T, Brembilla G, Brizmohun M, Tuazon J, Clemente J, Mathew M, Potyka I, Brew-Graves C, Markus J, Giganti F, Parry T, Haider A, Mallett S, Dudderidge T, Barrett T, Attard G, Moore C, Punwani S; CLIMATE Trial Management Group. The 'Comparison of diagnostic accuracy of Luminal Index and standard of care MRI for Accelerated deTEction of prostate cancer' (CLIMATE) trial protocol. BJU Int. 2026 Apr;137(4):611-618. doi: 10.1111/bju.70108. Epub 2026 Jan 25.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shonit Punwani principal investigator
University College, London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Luminal Index MRI (LI-MRI), LI-MRI targeted prostate biopsy and Plasma methylation signature (ctMethSig) in people with Prostate Cancer, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Trial Manager (02076795279, ncita.climate@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic accuracy of mp-MRI and LI-MRI (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05020522, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2023.