Renal Denervation in Diabetic Nephropathy

Diabetic Nephropathy Clinical Trial

— DERENEDIAB  

Official title:

Renal Denervation in Patients With Diabetic Nephropathy and Persistent Proteinuria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01588795
• Other study ID #: P110122
• Status: Completed
• Phase: Phase 4
• First received: April 18, 2012
• Last updated: May 30, 2016
• Start date: April 2012
• Est. completion date: January 2016

Study information

• Verified date: May 2016
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Committee for the Protection of Personnes
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases
• Persistent Proteinuria With Type II Diabetes
• Proteinuria

Intervention

Procedure:
• Percutaneous renal denervation and TMNS
Patients are treated with the renal denervation procedure after randomization and are maintained on standardized anti-proteinuric medications

Drug:
• Standardized antiproteinuric medication regimen includes an angiotensin receptor blocker , a diuretic , 25OH vitamin D3 and a statin
Patients are maintained on Standardized antiproteinuric medication regimen includes an angiotensin receptor blocker (irbesartan 300mg), a diuretic (furosemide 40mg or indapamide LP 1.5mg according to the eGFR), 25OH vitamin D3 and a statin (atorvastatin 20mg)

Locations

Country	Name	City	State
France	CIC Hopital europeen george pompidou	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	proteinuria/creatininuria ratio		from baseline to 1 year	No
Secondary	Number of patients with a decrease of the PU/CrU >50% ratio		from baseline to 1 year	No
Secondary	Evaluation of the slope of decay of the PU/CrU		from baseline to 1 year	No
Secondary	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	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	Yes
Secondary	Outcome of the GFR assessed by 51Cr-EDTA clearance	Only in the experimental arm	from randomisation to 1 year	Yes
Secondary	Decrease of the blood pressure assessed on ABPM		From randomisation to 1 year	No
Secondary	Anti-hypertensive regimen score		from baseline to 1 year	No
Secondary	Evaluation of the renal arterial anatomy	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 <	from baseline to 1 year	Yes
Secondary	Evaluation of safety and tolerance of renal denervation in diabetic patients with overt proteinuria	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	from baseline to 1 year	Yes
Secondary	Evaluate the outcome of biological parameters	eGFR (MDRD formula), proteinuria/creatininuria ratio	from baseline to 1 year	No
Secondary	Evaluate the diabetic neuropathy/dysautonomy	in the experimental:blood pressure in orthostatism, pulse wave velocimetry, RR interval on the Holter ECG, cutaneous baroreflex	from randomisation to 1 year	No
Secondary	Evaluate the outcome of specific kidney injury markers	in the experimental group:urinary levels of KIM1 and NGAL before and 1 year after the denervation	from randomisation to 1 year	Yes