Distal Renal Denervation to Prevent Renal Function Decline in Patients With T2DM and Hypertension

Not Applicable

Completed

• Conditions: Hypertension; Type 2 Diabetes Mellitus
• Interventions: Procedure: Anatomically optimized distal renal denervation

• Registration Number: NCT04948918
• Lead Sponsor: Tomsk National Research Medical Center of the Russian Academy of Sciences

Brief Summary

The aim of this study is to test the hypothesis that distal renal denervation (RDN) may delay or prevent the progressive decline of renal function in patients with type 2 diabetes mellitus and hypertension

Detailed Description

Detailed Description: Diabetes mellitus and hypertension are two major causes of chronic kidney disease (CKD) that starts as subclinical decline in renal function that silently progresses to symptomatic advanced stages associated with irreversible significant damage of the kidney structure. Recent major improvements in pharmacotherapy of hypertension and diabetes have substantially reduced the prevalence of cardiovascular complications, yet, the frequency of CKD remains largely unchanged. Renal denervation is a new minimally invasive method to create regional blockade of the renal sympathetic nerves that is currently used as non-pharmacological therapy of hypertension. The CKD is likewise mediated by overactivity of renal sympathetic system so that RDN has strong potential to prevent development or progression of CKD. The new anatomically optimized distal RDN may have additional benefit in this regard. Denervation of the distal vessels involved in tonic regulation of renal blood should cause a significant drop in renal vascular resistance and proportional increase in blood and oxygen supply to the kidney preventing/reducing chronic hypoxia of renal tissue that is major mechanism of CKD. The aim of this study is to prove the aforementioned concept. For this purpose the eligible patients with type 2 diabetes mellitus and hypertension will undergo distal renal denervation performed using dedicated radiofrequency catheter Symplicity Spyral. The changes in the kidney function and structure as well as BPs (office and ambulatory) will be assessed at baseline, 6 and 12 months post-procedure

Study Timeline

• Study Start: 2020-09-20
• Study First Submitted: 2021-06-24
• Study First Submitted QC: 2021-06-24
• Study First Posted: 2021-07-02
• Primary Completion: 2022-09-20
• Study Completion: 2023-09-20
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-27
• Last Update Posted: 2023-11-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• informed consent of participation in the study;
• systolic BP > 140 or diastolic BP > 90 mm Hg;
• type 2 diabetes mellitus (glucose tolerance test > 11.0 mmol/l, HbA1c>6,5%);

Exclusion Criteria

• secondary hypertension;
• type 1 diabetes mellitus;
• acute renal failure;
• traumatic kidney injury;
• toxic kidney injury;
• CKD G4 and G5 according to the KDIGO 2012;
• infectious diseases requiring active antibacterial and/or antiviral therapy;
• other severe diseases and conditions

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Distal renal denervation	Anatomically optimized distal renal denervation	The arm comprises patients undergoing distal bilateral radiofrequency renal denervation performed using Symplicity Spyral renal denervation system.

Primary Outcome Measures

Name	Time	Method
Change in estimated glomerular filtration rate renal function (eGFR)	from baseline to 12 months	eGFR calculated using CKD-EPI formula

Secondary Outcome Measures

Name	Time	Method
Change in eGFR	from baseline 12 months	eGFR calculated using CKD-EPI formula
Change in cystatin C levels	from baseline to 6 and 12 months	blood analysis
Change in office blood pressure levels (systolic/diastolic)	from baseline to 6 months and 12 months	Blood pressure measurement performed by physician in office
Change in 24-hour urinary albumin excretion	from baseline to 6 and 12 months	urinalysis
Change in peak linear blood flow velocity in the trunk and in segmental renal arteries	from baseline to 6 and 12 months	blood flow velocity assessed by Doppler flowmetry in the trunk of the renal arteries and in segmental renal arteries using averaged values
Change in ambulatory 24-hour blood pressure levels (24-h mean, daytime, nighttime; systolic/diastolic)	from baseline to 6 and 12 months	Mean values for respective periods calculated from ambulatory blood pressure monitoring performed using automatic measurement device
Change in renal resistive index in a trunk	from baseline to 6 and 12 months	resistive index calculated using blood flow velocity on Doppler ultrasound
Change in lipocalin 2 (NGAL) levels	from baseline to 6 and 12 months	blood analysis
Prognostic significance of baseline HbA1c value with regard to change in eGFR	from baseline to 6 and 12 months	Will be assessed from multiple regression model of linear dependence of change in eGFR on a number of independent variables including in addition to HbA1c also age, sex, baseline eGFR, and 24-h ambulatory systolic BP
Change in the cortical and medullary volume of the kidneys and their ratio according to MRI	from baseline to 12 months	Cortical and medullary volume measured using magnetic resonance imaging

Trial Locations

Locations (1)

Cardiology Research Institute, Tomsk National Research Medical Centre, Russian Academy of Sciences; 🇷🇺 Tomsk, Russian Federation