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

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

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

Study Overview

• Status: Completed
• Conditions: Hypertension; Type 2 Diabetes Mellitus
• Intervention / Treatment: Procedure: Anatomically optimized distal renal denervation

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 Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Tomsk, Russian Federation, 634012
    • Cardiology Research Institute, Tomsk National Research Medical Centre, Russian Academy of Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Distal renal denervation; The arm comprises patients undergoing distal bilateral radiofrequency renal denervation performed using Symplicity Spyral renal denervation system.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in estimated glomerular filtration rate renal function (eGFR)	eGFR calculated using CKD-EPI formula	from baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in eGFR	eGFR calculated using CKD-EPI formula	from baseline 12 months
Change in office blood pressure levels (systolic/diastolic)	Blood pressure measurement performed by physician in office	from baseline to 6 months and 12 months
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
Change in cystatin C levels	blood analysis	from baseline to 6 and 12 months
Change in lipocalin 2 (NGAL) levels	blood analysis	from baseline to 6 and 12 months
Change in 24-hour urinary albumin excretion	urinalysis	from baseline to 6 and 12 months
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
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
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
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

Collaborators and Investigators

• Sponsor: Tomsk National Research Medical Center of the Russian Academy of Sciences
• Investigators: Study Director: Alla Falkovskaya, MD, PhD, Cardiology Research Institute, Tomsk National Research Medical Centre, Russian Academy of Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2020
• Primary Completion (Actual): September 20, 2022
• Study Completion (Actual): September 20, 2023

Study Registration Dates

• First Submitted: June 24, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): July 2, 2021

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: hypertension; blood pressure; denervation; kidney; diabetes mellitus; renal function
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hypertension; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 005/e3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No