Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04114682 |
| Other study ID # |
CA064 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 27, 2020 |
| Est. completion date |
September 30, 2026 |
Study information
| Verified date |
November 2023 |
| Source |
Perspectum |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
MODIFY study is a multi-centre prospective, longitudinal, observational cohort study which
aims to recruit 150 adult patients with type 2 diabetes recruited from community, primary
care or secondary care settings. The total length of the study is 75 months. The aim of the
study is to develop an MRI-based method to identify whom amongst people with Type 2 diabetes
are at risk of further complications in their kidney, liver and cardiovascular system.
Description:
There has been a surge in incidence of the metabolic syndrome; a cluster of conditions which
increase the risk of, type 2 diabetes (T2D) (90% of diabetes cases), non-alcoholic fatty
liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cardiovascular disease
(including ischaemic heart disease and heart failure), ischaemic or haemorrhagic stroke
This project concentrates on T2D, a disease whose multiple patho-physiological defects
include; increased renal glucose re-absorption, decreased peripheral glucose utilisation,
increased hepatic glucose production due to insulin resistance, increased glucagon secretion,
reduced insulin secretion (pancreas), and incretin secretion (gastrointestinal tract)
Estimated UK prevalence of T2D is 5.26%. This represents 3.3 million people (comparatively in
the US, 9.1% or 26.44 million people), which equates to £8.8bn in associated healthcare costs
in UK.
Type 2 diabetes is associated with a heterogeneity in its aetiology - this is observed in its
clinical presentation and subsequent rate of progression. Further factors associated with T2D
include micro-and macrovascular complications and an observed decline in multiple organs
(end-organ damage). End-organ damage contributes to the clinical picture of individuals with
T2D and is demonstrated when observing the high prevalence of co-morbidities in this patient
cohort. For example, the presence of NAFLD is seen in 60% of T2D patients, along with a
34.2-50.7% presence of chronic kidney disease (CKD) and a 32.2% presence of cardiovascular
disease (CVD).
Currently, T2D and its complications are monitored using circulating plasma and serum
biomarkers. However, these lack sufficient sensitivity or specificity. An example of this is
highlighted in one researcher's preliminary data that suggests that 85% of obese people with
T2D had NAFLD, detected by MRI. However, a vast proportion of this patient cohort have
recorded normal biochemical biomarkers, such as Alanine Transaminase (ALT).
Metformin is typically the initially treatment for T2D. However, due to its progressive
nature, metformin monotherapy proves to be inadequate in maintaining long-term glycaemic
control. Metformin has been used safely and effectively for decades, but newer drugs are
becoming available. Numerous recent studies have shown that newer drug classes, including the
SGLT-2 inhibitors and GLP1 receptor agonists (GLP-1RA), have substantial beneficial effects
beyond modulation of glycaemic levels, and can confer protection against CVD and CKD. It is
now recommended that use of these drugs is advocated for high risk populations with evidence
of CKD or CVD.
This proposal aims to develop an MRI-based method that is able to identify the individuals at
high risk of disease complications, looking particularly at renal, hepatic and cardiovascular
pathology, and further compare this to the conventional biochemical approach. This has future
potential in assisting in the stratification of patients to the most appropriate tailored
treatment for their disease. The investigators will further evaluate the additional
synergistic value of incorporating MRI-metrics into patient pathways.
There is a healthcare need to provide further decision-making support for clinicians in the
care of patients at risk or diagnosed with T2D. This would combine multi-modality approaches,
an incorporation of biochemical evaluation and imaging techniques. There is also a pressing
need for treatment stratification to identify the T2D patients who would benefit from being
triaged to receive the newer, more expensive drugs. This would also empower patients and aid
in their engagement of the lifestyle changes often required for treatment. This should have
the added benefit of reducing associated NHS costs by minimising the pool of patients with
severe disease, who would be highlighted through early detection and early medical
management.
To address this growing need, the investigators propose adding a complementary imaging aspect
to the currently used biomarkers. MRI, specifically, provides excellent soft-tissue contrast.
Perspectum's LiverMultiScan is a quantitative multiparametric MRI method, FDA-cleared and
CE-marked, that is used to detect and stage early liver disease. It is already widely used in
pharmaceutical trials for NAFLD therapeutics. The MRI metrics from LiverMultiScan can
quantify changes to liver tissue characteristics, like fibro-inflammation and fat, as a
result of intervention (for example, bariatric surgery). The accuracy and reproducibility of
LiverMultiScan has been demonstrated in studies scanning patients within different MRI
scanners. It continues to be further supported by data from clinical trials in liver disease
cohorts, from comparative studies that include healthy controls, as well as whole-population
studies in the UK and US.
With this proposal the investigators aim to develop a new MRI image analysis technique,
"ATLAS", that builds on LiverMultiScan technology. the investigators also plan to gather
clinical evidence that will demonstrate the potential added value to the NHS, as well as
support future regulatory clearance. The phenotypical information that ATLAS delivers,
combined with information from circulating biomarkers, will form the basis of a future
clinical decision support tool for T2D.
Perspectum has pilot data showing that LiverMultiScan can estimate portal hypertension
(spleen), detect pancreatitis, and characterise the tissue of the kidneys.
This proposal will extend LiverMultiScan to each of the other relevant organs - pancreas,
kidneys and spleen. The technical development of "ATLAS" will be complemented by the
accumulation and analysis of clinical data, circulating biomarkers and imaging. This
information will be obtained from three diverse UK clinical centres (Liverpool, Oxford and
London).
The innovation comes from combining a number of quantitative MRI metrics to achieve this:
- volumes - for liver, spleen, kidneys, pancreas;
- fibroinflammation: cT1 and/or T1 - for liver, spleen, kidneys, pancreas;
- fat infiltration: PDFF - for liver, kidneys, pancreas;
- aortic distensibility and diameter. The investigators will also incorporate kidney
diffusion and renal flow. There will be strong patient and clinician involvement in the
collection of patient-reported experience and outcome measures throughout the study
(PREMs and PROMs), both qualitative and quantitative, to reflect the patients'
experience of the clinical care pathway.
The resulting MRI diagnostic solution will enable rapid and comprehensive stratification of
T2D and affiliated diseases (NAFLD, CKD, CVD), allowing clinicians to facilitate personalised
medicine. It is anticipated that adopting a clinical approach which utilises ATLAS will
result in substantial cost savings for the NHS and will help improve patient experience by
providing access to advanced treatments to those patients most at risk.
The main objective of this study is to assess the health of multiple organs over a period of
9 months, using multiparametric abdominal MRI, in patients with type 2 diabetes who have been
prescribed glucose lowering therapy (as per their standard of care).
This will be a multi-site study adopting a prospective, observational, longitudinal, cohort
study design. There will be no intervention to the standard of care. Participants will be
required to attend a screening visit and additional study visits on up to three time points -
baseline (visit 1), a visit within 21 days of baseline (visit 2) and at 9-months (visit 3).
The second and third visit will involve having a multiparametric MRI scan. Where possible,
some visits (the screening visit visit 1 or visit 1 /visit 2) may be on the same day or
within standard of care, depending on patient and MRI scanner availability.
Patients with type 2 diabetes and prescribed with glucose lowering therapy (as per standard
of care) will be recruited from community settings, primary care centres and diabetes clinics
within secondary care settings. The investigators aim to recruit patients who have been newly
prescribed medication; also those patients undergoing treatment intensification (when an
additional treatment is being considered due to evidence of poor glycaemic control), as per
their standard of care HbA1c level results. Clinical outcome measurements, blood samples and
urine samples will be collected to assess the response to standard of care treatment. There
will be an optional thoracic echocardiogram (ECHO) included at visit 2. This is a
non-invasive way in which the investigators can capture data to enable us to assess
cardiovascular disease.
Study participants will be enrolled in this study for a total of 5-years. During this time,
consented participants will be asked to attend for up to 3 study visits: Visit 1 (baseline),
Visit 2 and Visit 3. Further to this, participants will be asked to give consent to the
review of their medical records at 3 time points - years 1, 3, and 5, following baseline
assessment. This review will be conducted by authorised study investigators who will obtain
clinical outcome measures relating to the study objectives, for example, measures of liver or
kidney function.
The primary endpoint of the study is to compare the MRI metrics for liver fibroinflammation
in those patients with type 2 diabetes at baseline vs. individuals who are healthy and
non-diabetic. Values for the healthy, non-diabetics will be provided from data from the UK
Biobank (UKBB) and will be selected based on the matching of gender, age, ethnicity to the
patients from this study with type 2 diabetes. Analysis will be based on a two-sample,
two-sided t-test. The sample size required to perform a t-test with 90% power and alpha of
0.05 would require n=150.
Participants will be identified from the community, primary care and secondary care
diabetes;appointments; specifically those patients with type 2 diabetes who are prescribed
glucose lowering treatment as per their standard of care. A member of the clinical care team
will provide potential participants with a study invitation letter and an accompanying
Participant Information Leaflet (PIL) in the following places: Liverpool Diabetes
Partnership/University Hospital Aintree, The Oxford Centre for Diabetes, Endocrinology and
Metabolism (OCDEM) Oxford University Hospitals NHS Foundation Trust, The Royal Free London
NHS Foundation Trust - Diabetes Department.
At each study centre, posters will be displayed around the hospitals, University departmental
buildings and GP practices so that potential participants can also self-refer into the study
by contacting the study team directly. The study will also be advertised on social media
platforms (for example, Twitter and Facebook), Perspectum Diagnostics Ltd's website and also
hospital websites. . Once a potential participant has been identified by any of these means,
and has expressed an interest in taking part in the study, they will be sent a Participant
Information Leaflet (PIL) to read. They will be allowed as much time as they require to
understand the details of the study and what's involved before signing the consent form.
