Clinical Utility of a Genomic Predictor Test on the Management of Cardiorenal Complications of Type 2 Diabetes

Official title

New GENOmic Predictor for COmplications Risk in Type 2 DIAbetes

Overview

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.

Detailed description

Type 2 diabetes (T2D) increases the risk of developing serious cardiovascular and kidney complications that represent a major burden for both patients and our healthcare system. Currently, patients with T2D are treated according to guidelines, with varied results in terms of systolic blood pressure (SBP), blood glucose (HbA1c), urine albumin-creatinine ratio (UACR) and glomerular filtration rate (GFR) target achievement.

OPTITHERA has developed the first genomic test to predict the risk of cardiorenal complications that will allow early and personalized treatment of patients with T2D who are at high risk using Polygenic risk score.

It is proposed that knowledge of the risk of developing complications of diabetes will have a positive effect on the care pathway of diabetic patients: the patient will be able to actively participate in their care and their doctor will be able to adapt his treatment to his personal risk, especially if his patient is at high risk of complications.

Objective: To provide Real World Evidence (RWE) on the impact of the result of a PRS prediction test on the risk of complications of T2D, so that patients at high risk of complications achieve, over an 18-month period, recommended targets for systolic blood pressure (≤130 mmHg) or HbA1c (\<7.0%), or decreased albuminuria grade, GFR decline, while avoiding severe hypoglycemia and falls.

This will be demonstrated as a significant improvement in composite value including HbA1c or systolic blood pressure (SBP) or albuminuria (UACR).

Methodology: Multicenter Study: A) Pragmatic trial designed to evaluate the effectiveness of GENOCORDIA PRS testing in real-life routine practice conditions.

B) Randomization of participants into informed and uninformed populations of the PRS test result. C) Adaptive trial for the treatment of subjects initially uninformed of their PRS test result.

Estimated number of participants: 2714 participants randomized into two groups. Estimated study enrollment duration= 9 months. Estimated total study duration = 36 months. 18 months follow-up (7 visits).

Interventions

• Device Polygenic Risk Score
  The Polygenic Risk Score (PRS) is a Class II software as a medical device (SaMD) that estimates a person's level of risk of developing a disease or associated complications before clinical signs appear. The device uses the genomic profile of the person in combination with some clinical data (i.e., age, sex, age of onset of diabetes) to compute this risk. This device further provides recommendations for personalized management of T2D for patients based on their risk score.

Primary outcome measures

• Composite endpoint consisting of HbA1c, SBP, albuminuria or GFR [Time frame: Visit to visit up to 18 months]

Secondary outcome measures (1)

• Medications for blood pressure, blood glucose and lipids [Time frame: Visit to vist up to 18 months]

Eligibility criteria

Inclusion criteria

• Adult patients with T2D of both sexes regardless of ethnicity, level of diabetes control and presence of complications.
• Able to visit the study site 7 times
• Able and willing to provide informed consent to the clinical and PRS parts of the study.

Exclusion criteria

• Any condition that may impact participation in a real-world study according to the treating physician.
• People with a high frailty index as no benefit of therapeutic intensification has been demonstrated in these diabetic patients.
• People who refuse to be informed of their cardiorenal risk score.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

Canada · 2 centers

• CHUM — Montreal
• ELNA Medical — Montreal

Publications

• Tremblay J, Haloui M, Attaoua R, Tahir R, Hishmih C, Harvey F, Marois-Blanchet FC, Long C, Simon P, Santucci L, Hizel C, Chalmers J, Marre M, Harrap S, Cifkova R, Krajcoviechova A, Matthews DR, Williams B, Poulter N, Zoungas S, Colagiuri S, Mancia G, Grobbee DE, Rodgers A, Liu L, Agbessi M, Bruat V, Fave MJ, Harwood MP, Awadalla P, Woodward M, Hussin JG, Hamet P. Polygenic risk scores predict diab PMID 34226943

Identifiers

NCT: NCT06586203 · OPT0003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗