Trial Summary
What is the purpose of this trial?The goal of this pragmatic trial is to provide Real World Evidence (RWE) on the impact of the result of a polygenic risk prediction test of cardiorenal complications of T2D, so that more patients at high risk of these complications achieve over an 18 months period, recommended therapeutic targets.
This will be demonstrated as a significant improvement in a composite value including HbA1c or systolic blood pressure (SBP) or albuminuria (UACR), or glomerular filtration rate (GFR) lowering.
Researchers will compare the recommended therapeutic targets of uninformed and informed patients to see if the knowledge of the risk by the patients and their treating physicians improves achievement of these targets.
Participants will:
Have a saliva sampling to determine the genetic risk. Visit the clinic once every 3 months for checkups and tests Answer two questionnaires on quality of life.
Is the treatment in the trial 'Genetic Test for Cardiorenal Complications in Type 2 Diabetes' a promising treatment?Yes, the treatment is promising because it uses genetic information to predict and manage complications in type 2 diabetes, potentially leading to better outcomes by identifying high-risk patients early.68101113
What safety data exists for the genetic test for cardiorenal complications in type 2 diabetes?The provided research does not directly address safety data for the genetic test, such as the Polygenic Risk Score (PRS) or Genetic Risk Score (GRS), in predicting cardiorenal complications in type 2 diabetes. The studies focus on the economic evaluation, predictive capabilities, and genetic factors related to diabetic nephropathy and chronic kidney disease, but do not mention specific safety data or adverse effects associated with the use of these genetic tests.25679
What data supports the idea that Genetic Test for Cardiorenal Complications in Type 2 Diabetes (also known as: Polygenic Risk Score, Genetic Risk Score, PRS) is an effective treatment?The available research shows that while genetic information, like Polygenic Risk Scores (PRS), can help identify risk factors for complications in type 2 diabetes, they do not currently improve the accuracy of predicting kidney damage over existing clinical methods. For example, a study found that many genetic markers were linked to kidney issues, but they didn't enhance prediction accuracy compared to standard tests. This suggests that while PRS might offer some insights, they are not yet proven to be more effective than current methods for managing cardiorenal complications in type 2 diabetes.134612
Do I have to stop taking my current medications for this trial?The trial protocol does not specify whether you need to stop taking your current medications. It seems likely that you can continue your current medications, but you should confirm with the trial coordinators.
Eligibility Criteria
This trial is for individuals with Type 2 Diabetes who may also have cardiovascular disease or diabetic kidney disease. Participants will provide a saliva sample, attend clinic visits every three months, and complete quality of life questionnaires.Inclusion Criteria
I can visit the study site 7 times.
Exclusion Criteria
I refuse to know my heart and kidney risk score.
Treatment Details
The study tests if knowing one's genetic risk for cardiorenal complications (heart and kidney problems) from Type 2 Diabetes helps achieve better health targets over 18 months. This includes blood sugar levels, blood pressure, urine albumin levels, and kidney function.
2Treatment groups
Active Control
Group I: InformedActive Control1 Intervention
Intervention group tested and informed of the Polygenic risk score test result at the start of the study
Group II: Not initially informedActive Control1 Intervention
Control group: tested but not informed of the Polygenic Risk Score test result at the start of the study.
Find a clinic near you
Research locations nearbySelect from list below to view details:
CHUMMontreal, Canada
ELNA MedicalMontreal, Canada
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Who is running the clinical trial?
OptitheraLead Sponsor
ELNA MedicalCollaborator
Genome CanadaCollaborator
Genome QuebecCollaborator
References
Angiotensin-converting enzyme (ACE) gene polymorphism in type II diabetic patients with increased albumin excretion rate. [2019]Approximately one in three patients with diabetes is at risk of developing kidney disease, despite current methods of treatment. It has long been suspected that diabetic kidney disease has a genetic basis, but this has been difficult to prove. Polymorphisms of the angiotensin-converting enzyme (ACE) gene have been shown to be related to the occurrence of nephropathy in type I diabetic patients. This study showed that there was no association in the ACE genotype frequency and increased albumin excretion rate in type II diabetic patients.
[Genetic factors with significance in pathogenesis of diabetic nephropathy--the role of polymorphism of renin-angiotensin system genes]. [2006]The article presents the contemporary view about the role of polymorphisms of renin-angiotensin system genes in the pathogenesis of diabetic nephropathy in subjects with type 1 and type 2 diabetes.
ACE gene polymorphism as a prognostic indicator in patients with type 2 diabetes and established renal disease. [2022]To investigate whether the DD genotype is a predictor of mortality and of the decline in renal function in patients with type 2 diabetes and established nephropathy.
[Genetics of diabetic complications: nephropathy]. [2019]Diabetic nephropathy is present in 35 to 45% of Type 1 diabetic patients after 15-20 yrs of diabetes duration. Glycaemic control and diabetes duration are the major risk factors for diabetic nephropathy. Hypertension which is twice as common in diabetics than in the general population, as well as ethnic origin play an important role too. However, as not all diabetic patients will develop diabetic nephropathy, this support the hypothesis for factors of genetic susceptibility (or of protection!) to diabetic nephropathy. Familial aggregation studies supporting this concept of genetic susceptibility, and studies on candidate genes polymorphisms and their association (or lack of association) with diabetic nephropathy (angiotensin-converting enzyme, angiotensinogen and atrial natriuretic peptide genes) are reviewed. Available data from candidate genes studies support a possible implication of vasoactive genes polymorphisms in the development of diabetic nephropathy, but the risk appears to be weak. Ongoing and future studies should aim to detect gene polymorphisms with strong effects, or to identify the association and/or interaction between polymorphisms and diabetic nephropathy.
Coding variants in nephrin (NPHS1) and susceptibility to nephropathy in African Americans. [2022]Presumed genetic risk for diabetic and nondiabetic end stage renal disease is strong in African Americans.
Biomarkers of vascular complications in type 2 diabetes. [2015]People with T2D are at substantially increased risk of developing severe complications, (coronary heart disease, stroke, retinopathy and nephropathy). Clinicians have an important responsibility to identify those patients who, because they are at high risk, will benefit more from a preventive program or intensified therapy. However, due to the limited accuracy of the predictive tests, and limited effectiveness of preventive measures, clinicians and their patients show a suboptimal compliance to such programs. An improved risk assessment will positively impact cost/benefit ratios, opening the door for new intervention. Research involving human genetic or genomic information becomes increasingly powerful and, in conjunction with other novel biomarkers, together with personal or health data, will offer new tools for harnessing risk factors underlying complex (multi-factorial) diseases such as T2D and its complications. Altogether, there is a rationale to develop early biomarkers with improved predictive value for vascular complications of T2D by integrating patients' genetic information with traditional and emerging biomarkers.
Genetic risk score and risk of stage 3 chronic kidney disease. [2022]We developed a genetic risk score (GRS) and examined whether the GRS may predict incident stage 3 chronic kidney disease (CKD) independent of common clinical risk factors.
Genetic risk score for risk prediction of diabetic nephropathy in Han Chinese type 2 diabetes patients. [2022]We evaluated whether genetic information could offer improvement on risk prediction of diabetic nephropathy (DN) while adding susceptibility variants into a risk prediction model with conventional risk factors in Han Chinese type 2 diabetes patients. A total of 995 (including 246 DN cases) and 519 (including 179 DN cases) type 2 diabetes patients were included in derivation and validation sets, respectively. A genetic risk score (GRS) was constructed with DN susceptibility variants based on findings of our previous genome-wide association study. In derivation set, areas under the receiver operating characteristics (AUROC) curve (95% CI) for model with clinical risk factors only, model with GRS only, and model with clinical risk factors and GRS were 0.75 (0.72-0.78), 0.64 (0.60-0.68), and 0.78 (0.75-0.81), respectively. In external validation sample, AUROC for model combining conventional risk factors and GRS was 0.70 (0.65-0.74). Additionally, the net reclassification improvement was 9.98% (P = 0.001) when the GRS was added to the prediction model of a set of clinical risk factors. This prediction model enabled us to confirm the importance of GRS combined with clinical factors in predicting the risk of DN and enhanced identification of high-risk individuals for appropriate management of DN for intervention.
Economic Evaluation of a New Polygenic Risk Score to Predict Nephropathy in Adult Patients With Type 2 Diabetes. [2021]The current screening method for diabetic nephropathy (DN) is based on detection of albumin in the urine and decline of glomerular filtration rate. The latter usually occurs relatively late in the course of the disease. A polygenic risk score (PRS) was recently developed for early prediction of the risk for patients with type 2 diabetes (T2D) to develop DN. The aim of this study was to assess the economic impact of the implementation of the PRS for early prediction of DN in patients with T2D compared with usual screening methods in Canada.
Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control. [2022]Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk.
Systematic Heritability and Heritability Enrichment Analysis for Diabetes Complications in UK Biobank and ACCORD Studies. [2023]Diabetes-related complications reflect longstanding damage to small and large vessels throughout the body. In addition to the duration of diabetes and poor glycemic control, genetic factors are important contributors to the variability in the development of vascular complications. Early heritability studies found strong familial clustering of both macrovascular and microvascular complications. However, they were limited by small sample sizes and large phenotypic heterogeneity, leading to less accurate estimates. We take advantage of two independent studies-UK Biobank and the Action to Control Cardiovascular Risk in Diabetes trial-to survey the single nucleotide polymorphism heritability for diabetes microvascular (diabetic kidney disease and diabetic retinopathy) and macrovascular (cardiovascular events) complications. Heritability for diabetic kidney disease was estimated at 29%. The heritability estimate for microalbuminuria ranged from 24 to 60% and was 41% for macroalbuminuria. Heritability estimates of diabetic retinopathy ranged from 6 to 33%, depending on the phenotype definition. More severe diabetes retinopathy possessed higher genetic contributions. We show, for the first time, that rare variants account for much of the heritability of diabetic retinopathy. This study suggests that a large portion of the genetic risk of diabetes complications is yet to be discovered and emphasizes the need for additional genetic studies of diabetes complications.
Albuminuria-Related Genetic Biomarkers: Replication and Predictive Evaluation in Individuals with and without Diabetes from the UK Biobank. [2023]Increased albuminuria indicates underlying glomerular pathology and is associated with worse renal disease outcomes, especially in diabetic kidney disease. Many single nucleotide polymorphisms (SNPs), associated with albuminuria, could be potentially useful to construct polygenic risk scores (PRSs) for kidney disease. We investigated the diagnostic accuracy of SNPs, previously associated with albuminuria-related traits, on albuminuria and renal injury in the UK Biobank population, with a particular interest in diabetes. Multivariable logistic regression was used to evaluate the influence of 91 SNPs on urine albumin-to-creatinine ratio (UACR)-related traits and kidney damage (any pathology indicating renal injury), stratifying by diabetes. Weighted PRSs for microalbuminuria and UACR from previous studies were used to calculate the area under the receiver operating characteristic curve (AUROC). CUBN-rs1801239 and DDR1-rs116772905 were associated with all the UACR-derived phenotypes, in both the overall and non-diabetic cohorts, but not with kidney damage. Several SNPs demonstrated different effects in individuals with diabetes compared to those without. SNPs did not improve the AUROC over currently used clinical variables. Many SNPs are associated with UACR or renal injury, suggesting a role in kidney dysfunction, dependent on the presence of diabetes in some cases. However, individual SNPs or PRSs did not improve the diagnostic accuracy for albuminuria or renal injury compared to standard clinical variables.
Genetic risk scores identify people at high risk of developing diabetic kidney disease: A systematic review. [2023]Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). Measures to prevent and treat DKD require better identification of patients most at risk. In this systematic review, we summarise the existing evidence of genetic risk scores (GRSs) and their utility for predicting DKD in people with type 1 or type 2 diabetes.