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

Hypertension Clinical Trial

— REFRAIN  

Official title:

Efficacy of Distal Renal Denervation for Preventing Decline in Renal Function in Patients With Type 2 Diabetes Mellitus and Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04948918
• Other study ID #: 005/e3
• Status: Completed
• Phase: N/A
• Start date: September 20, 2020
• Est. completion date: September 20, 2023

Study information

• Verified date: November 2023
• Source: Tomsk National Research Medical Center of the Russian Academy of Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: September 20, 2023
• Est. primary completion date: September 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Hypertension
• Type 2 Diabetes Mellitus

Intervention

Procedure:
• Anatomically optimized distal renal denervation
Bilateral radiofrequency renal denervation will be performed using Symplicity Spyral renal denervation system. Generally, at least two separate applications of radiofrequency energy will be performed in each segmental branch of renal artery. Each application will be done through 4 electrodes deployed in helical manner according to the design of the catheter

Locations

Country	Name	City	State
Russian Federation	Cardiology Research Institute, Tomsk National Research Medical Centre, Russian Academy of Sciences	Tomsk

Sponsors (1)

Lead Sponsor	Collaborator
Tomsk National Research Medical Center of the Russian Academy of Sciences

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in estimated glomerular filtration rate renal function (eGFR)	eGFR calculated using CKD-EPI formula	from baseline to 12 months
Secondary	Change in eGFR	eGFR calculated using CKD-EPI formula	from baseline 12 months
Secondary	Change in office blood pressure levels (systolic/diastolic)	Blood pressure measurement performed by physician in office	from baseline to 6 months and 12 months
Secondary	Change in ambulatory 24-hour blood pressure levels (24-h mean, daytime, nighttime; systolic/diastolic)	Mean values for respective periods calculated from ambulatory blood pressure monitoring performed using automatic measurement device	from baseline to 6 and 12 months
Secondary	Change in cystatin C levels	blood analysis	from baseline to 6 and 12 months
Secondary	Change in lipocalin 2 (NGAL) levels	blood analysis	from baseline to 6 and 12 months
Secondary	Change in 24-hour urinary albumin excretion	urinalysis	from baseline to 6 and 12 months
Secondary	Change in the cortical and medullary volume of the kidneys and their ratio according to MRI	Cortical and medullary volume measured using magnetic resonance imaging	from baseline to 12 months
Secondary	Prognostic significance of baseline HbA1c value with regard to change in eGFR	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	from baseline to 6 and 12 months
Secondary	Change in renal resistive index in a trunk	resistive index calculated using blood flow velocity on Doppler ultrasound	from baseline to 6 and 12 months
Secondary	Change in peak linear blood flow velocity in the trunk and in segmental renal arteries	blood flow velocity assessed by Doppler flowmetry in the trunk of the renal arteries and in segmental renal arteries using averaged values	from baseline to 6 and 12 months