Renal Denervation in Diabetic Nephropathy

Phase 4

Completed

• Conditions: Diabetic Nephropathy; Persistent Proteinuria With Type II Diabetes
• Interventions: Procedure: Percutaneous renal denervation and TMNS; Drug: Standardized antiproteinuric medication regimen includes an angiotensin receptor blocker , a diuretic , 25OH vitamin D3 and a statin

• Registration Number: NCT01588795
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The DERENEDIAB study is a proof-of-concept, multi-center, prospective, open, randomized, controlled study of the effectiveness of renal denervation in addition to standardized medical treatment compared to medical treatment alone in diabetic subjects with diabetic nephropathy and resistant proteinuria. Bilateral renal denervation will be performed using the Symplicity Catheter - a percutaneous system that delivers radiofrequency (RF) energy through the luminal surface of the renal artery.

Detailed Description

The DERENEDIAB study is a proof-of-concept multi-center, prospective, open, randomized, controlled study of the effectiveness of renal denervation in addition to standardized medical treatment compared to medical treatment alone in diabetic subjects with diabetic nephropathy and resistant proteinuria. Bilateral renal denervation will be performed using the Symplicity Catheter - a percutaneous system that delivers radiofrequency (RF) energy through the luminal surface of the renal artery.

Study Timeline

• Study Start: 2012-04
• Study First Submitted: 2012-04-18
• Study First Submitted QC: 2012-04-27
• Study First Posted: 2012-05-01
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-30
• Last Update Posted: 2016-06-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• Type 2 diabetes mellitus male or female patient
• Individual is > 18 and ≤ 75 years old
• Diabetic nephropathy (if no pathological examination, diagnosis based on the association of history of diabetes, diabetic retinopathy and no hematuria)
• Proteinuria/creatininuria ratio > 0.1 g/mmol lasting for 8 weeks
• Under stable medication regimen including for at least 2 months full tolerated doses of al least 1 RAAS blocker (ACEI, renin inhibitor, ARB) and a diuretic
• 2 functional kidneys sizing ≥ 90 mm; eGFR > 20 mL/min/1.73m² (MDRD formula
• Suitable aorto-renal vascular anatomy compatible with the endovascular denervation procedure; Informed consent has been signed
• Health insurance policy active

Exclusion Criteria

• Patients with an estimated glomerular filtration rate (eGFR) of less than 20 mL/min/1.73 m2
• Patients unable to sign an informed consent, to understand the protocol, living too far from the specialized center
• Non-diabetic renal disease
• Patients with severe hypertension (grade 3 ESH classification)
• Kaliemia ≥ 6mmol/L
• History of nephrogenic fibrosis-induced MRI contrast media
• Patient with single functioning kidney
• Patient with contrast media allergy
• Patient with any implantable device incompatible with low frequency waves delivery
• Patient with contra-indication to the anti-proteinuric standardized medication regimen
• Patient with transient or fixed cerebral ischemia within 3 months before inclusion
• Patient with myocardial infarction, unstable angina pectoris, coronary bypass or percutaneous angioplasty within 3 months before inclusion
• Patient with asthma or chronic obstructive pulmonary disease with a contra-indication to beta-blockers medication
• Patient with type 1 diabetes mellitus
• Uncontrolled type 2 diabetes mellitus (Hb1Ac > 10%)
• Patient with malignancy within the 5 past years
• Patient with any medical or surgical condition that could worsen the risk of the study, according to the investigator; Patient with chronic alcohol consumption
• Patient with atrial fibrillation and/or a brachial circumference of ≥ 42cm
• Patient is pregnant, nursing or planning to be pregnant

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Denervation + TMNS	Percutaneous renal denervation and TMNS	Patients are treated with the renal denervation procedure after randomization and are maintained on standardized anti-proteinuric medications
TMNS	Standardized antiproteinuric medication regimen includes an angiotensin receptor blocker , a diuretic , 25OH vitamin D3 and a statin	Patients are maintained on standardized anti-proteinuric medications

Primary Outcome Measures

Name	Time	Method
proteinuria/creatininuria ratio	from baseline to 1 year

Secondary Outcome Measures

Name	Time	Method
eGFR is estimated by the MDRD formula, and is expressed in mL/min/1.73m². The direct GFR will be assessed by measuring the 51Cr-EDTA plasmatic clearance	from baseline to 1 year	eGFR is estimated by the MDRD formula, and is expressed in mL/min/1.73m². The direct GFR will be assessed by measuring the 51Cr-EDTA plasmatic clearance
Outcome of the GFR assessed by 51Cr-EDTA clearance	from randomisation to 1 year	Only in the experimental arm
Number of patients with a decrease of the PU/CrU >50% ratio	from baseline to 1 year
Evaluation of the slope of decay of the PU/CrU	from baseline to 1 year
Evaluation of the renal arterial anatomy	from baseline to 1 year	in the experimental group:number of principal renal artery. Should be 1/ kidney of at least 4mm diameter and 10mm long. One accessory artery is acceptable if \<
Decrease of the blood pressure assessed on ABPM	From randomisation to 1 year
Anti-hypertensive regimen score	from baseline to 1 year
Evaluation of safety and tolerance of renal denervation in diabetic patients with overt proteinuria	from baseline to 1 year	in the experimental group:Occurrence of adverse events: acute renal failure, damage on the renal artery (dissection, perforation, thrombosis), allergy to the contrast media, worsening of any dysautonomia
Evaluate the outcome of biological parameters	from baseline to 1 year	eGFR (MDRD formula), proteinuria/creatininuria ratio
Evaluate the diabetic neuropathy/dysautonomy	from randomisation to 1 year	in the experimental:blood pressure in orthostatism, pulse wave velocimetry, RR interval on the Holter ECG, cutaneous baroreflex
Evaluate the outcome of specific kidney injury markers	from randomisation to 1 year	in the experimental group:urinary levels of KIM1 and NGAL before and 1 year after the denervation

Trial Locations

Locations (1)

CIC Hopital europeen george pompidou; 🇫🇷 Paris, France