Genetic Test for Cardiorenal Complications in Type 2 Diabetes

(GENOCORDIA Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Pavel Hamet, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Optithera

Disqualifiers: High frailty index, others

No Placebo Group

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.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Polygenic Risk Score, Genetic Risk Score, PRS for cardiorenal complications in Type 2 Diabetes?

Research suggests that using genetic information, like Polygenic Risk Scores (PRS), could help identify people at higher risk for complications in Type 2 Diabetes, potentially leading to better prevention strategies. However, current studies indicate that PRS does not significantly improve the prediction of kidney issues over existing clinical methods. ^{1 2 3 4 5}

How does the genetic test for cardiorenal complications in type 2 diabetes differ from other treatments?

This genetic test is unique because it uses genetic information to predict the risk of developing heart and kidney complications in people with type 2 diabetes, allowing for earlier and more personalized interventions compared to traditional methods that rely solely on clinical risk factors. ^{4 6 7 8 9}

Research Team

Pavel Hamet, MD, PhD

Principal Investigator

CHUM

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

Able and willing to provide informed consent to the clinical and PRS parts of the study

I can visit the study site 7 times.

I am an adult with type 2 diabetes.

Exclusion Criteria

I am considered frail and have diabetes.

Any condition that may impact participation in a real-world study according to the treating physician

I refuse to know my heart and kidney risk score.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genomic Testing

Participants undergo saliva sampling to determine genetic risk using a polygenic risk score test

1 week

1 visit (in-person)

Treatment

Participants receive personalized treatment based on their genomic risk score, with regular checkups every 3 months

18 months

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on achieving therapeutic targets

4 weeks

Treatment Details

Interventions

• Polygenic Risk Score (Genomic Predictor Test)

Trial Overview 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.

Participant Groups

Group I: Informed Active Control 1 Intervention

Intervention group tested and informed of the Polygenic risk score test result at the start of the study

Group II: Not initially informed Active Control 1 Intervention

Control group: tested but not informed of the Polygenic Risk Score test result at the start of the study.

Who Is Running the Clinical Trial?

Optithera

Lead Sponsor

Trials

1

Recruited

2,700+

ELNA Medical

Collaborator

Trials

1

Recruited

2,700+

Genome Canada

Collaborator

Trials

17

Recruited

34,400+

Genome Quebec

Collaborator

Trials

8

Recruited

19,800+

Findings from Research

In a study of 56 Maltese Caucasian patients with type 2 diabetes and nephropathy, those with the DD genotype of the ACE gene experienced a significantly faster decline in kidney function, with a GFR decrease of -7.76 ml/min/year compared to -1.17 ml/min/year in those with ID or II genotypes.

The 3-year mortality rate was notably higher in patients with the DD genotype at 45.2%, compared to 20.0% in those with ID/II genotypes, indicating that the DD genotype is a strong predictor of both renal decline and mortality in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACE gene polymorphism as a prognostic indicator in patients with type 2 diabetes and established renal disease. Fava, S., Azzopardi, J., Ellard, S., et al.[2022]

Diabetic nephropathy affects 35 to 45% of Type 1 diabetes patients after 15-20 years, with glycaemic control and diabetes duration being the main risk factors.

Genetic susceptibility may play a role in the development of diabetic nephropathy, as not all diabetic patients experience this condition, suggesting the need for further research into specific gene polymorphisms that could influence risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Genetics of diabetic complications: nephropathy]. Jeunemaitre, X.[2019]

Individuals with Type 2 Diabetes (T2D) face a higher risk of severe complications like heart disease and stroke, highlighting the need for effective risk assessment to identify those who would benefit most from preventive measures.

Integrating genetic information with traditional and new biomarkers could enhance the predictive accuracy for vascular complications in T2D, potentially leading to better-targeted interventions and improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers of vascular complications in type 2 diabetes. Tremblay, J., Hamet, P.[2015]

In a study of the UK Biobank population, certain single nucleotide polymorphisms (SNPs) associated with albuminuria were found to correlate with urine albumin-to-creatinine ratio (UACR) traits, but they did not enhance the diagnostic accuracy for kidney damage beyond existing clinical measures.

The research highlighted that while some SNPs showed different effects in diabetic versus non-diabetic individuals, they did not significantly improve the prediction of albuminuria or renal injury, indicating that current clinical variables remain more effective for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albuminuria-Related Genetic Biomarkers: Replication and Predictive Evaluation in Individuals with and without Diabetes from the UK Biobank. Cañadas-Garre, M., Kunzmann, AT., Anderson, K., et al.[2023]

The study found that genetic factors significantly contribute to the heritability of diabetes-related complications, with estimates showing 29% heritability for diabetic kidney disease and varying heritability for microalbuminuria and diabetic retinopathy, indicating a strong genetic influence on these conditions.

Rare genetic variants were identified as major contributors to the heritability of diabetic retinopathy, highlighting that much of the genetic risk for diabetes complications remains to be uncovered, which calls for further genetic research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Heritability and Heritability Enrichment Analysis for Diabetes Complications in UK Biobank and ACCORD Studies. Kim, J., Jensen, A., Ko, S., et al.[2023]

In a study involving 995 type 2 diabetes patients, the addition of a genetic risk score (GRS) to conventional risk factors improved the prediction of diabetic nephropathy (DN) risk, with an AUROC of 0.78 compared to 0.75 for clinical factors alone.

The model combining GRS and clinical factors also showed a significant net reclassification improvement of 9.98%, indicating that genetic information can enhance the identification of high-risk individuals for better management of DN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic risk score for risk prediction of diabetic nephropathy in Han Chinese type 2 diabetes patients. Liao, LN., Li, TC., Li, CI., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Angiotensin-converting enzyme (ACE) gene polymorphism in type II diabetic patients with increased albumin excretion rate. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

ACE gene polymorphism as a prognostic indicator in patients with type 2 diabetes and established renal disease. [2022]

3. France pubmed.ncbi.nlm.nih.gov

[Genetics of diabetic complications: nephropathy]. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Biomarkers of vascular complications in type 2 diabetes. [2015]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Albuminuria-Related Genetic Biomarkers: Replication and Predictive Evaluation in Individuals with and without Diabetes from the UK Biobank. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Systematic Heritability and Heritability Enrichment Analysis for Diabetes Complications in UK Biobank and ACCORD Studies. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Genetic risk score for risk prediction of diabetic nephropathy in Han Chinese type 2 diabetes patients. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Genetic risk scores identify people at high risk of developing diabetic kidney disease: A systematic review. [2023]