Renal Denervation in Diabetic Nephropathy - Full Text View

Purpose

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.

Condition	Intervention	Phase
Diabetic Nephropathy Persistent Proteinuria With Type II Diabetes	Procedure: Percutaneous renal denervation and TMNS Drug: Standardized antiproteinuric medication regimen includes an angiotensin receptor blocker , a diuretic , 25OH vitamin D3 and a statin	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Renal Denervation in Patients With Diabetic Nephropathy and Persistent Proteinuria

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 2 Diabetic Kidney Problems Vitamin D

Drug Information available for: Cholecalciferol Vitamin D

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

proteinuria/creatininuria ratio [ Time Frame: from baseline to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of patients with a decrease of the PU/CrU >50% ratio [ Time Frame: from baseline to 1 year ] [ Designated as safety issue: No ]
Evaluation of the slope of decay of the PU/CrU [ Time Frame: from baseline to 1 year ] [ Designated as safety issue: No ]
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 [ Time Frame: from baseline to 1 year ] [ Designated as safety issue: Yes ]
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 [ Time Frame: from randomisation to 1 year ] [ Designated as safety issue: Yes ]
Only in the experimental arm
Decrease of the blood pressure assessed on ABPM [ Time Frame: From randomisation to 1 year ] [ Designated as safety issue: No ]
Anti-hypertensive regimen score [ Time Frame: from baseline to 1 year ] [ Designated as safety issue: No ]
Evaluation of the renal arterial anatomy [ Time Frame: from baseline to 1 year ] [ Designated as safety issue: Yes ]
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 <
Evaluation of safety and tolerance of renal denervation in diabetic patients with overt proteinuria [ Time Frame: from baseline to 1 year ] [ Designated as safety issue: Yes ]
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 [ Time Frame: from baseline to 1 year ] [ Designated as safety issue: No ]
eGFR (MDRD formula), proteinuria/creatininuria ratio
Evaluate the diabetic neuropathy/dysautonomy [ Time Frame: from randomisation to 1 year ] [ Designated as safety issue: No ]
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 [ Time Frame: from randomisation to 1 year ] [ Designated as safety issue: Yes ]
in the experimental group:urinary levels of KIM1 and NGAL before and 1 year after the denervation

Estimated Enrollment:	120
Study Start Date:	April 2012
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Denervation + TMNS Patients are treated with the renal denervation procedure after randomization and are maintained on standardized anti-proteinuric medications	Procedure: Percutaneous renal denervation and TMNS Patients are treated with the renal denervation procedure after randomization and are maintained on standardized anti-proteinuric medications
Active Comparator: TMNS Patients 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)

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01588795

Contacts

Contact: Guillaume Bobrie, MD	+33 1 56 09 37 71	guillaume.bobrie@egp.aphp.fr
Contact: Marc SAPOVAL, PD, PhD	00 33 (1) 56 09 37 40	marc.sapoval2@egp.aphp.fr

Locations

France
CIC Hopital europeen george pompidou	Recruiting
Paris, France, 75015
Contact: Guillaume Bobrie, MD 00 33 (1) 56 09 37 71 guillaume.bobrie@egp.aphp.fr
Contact: Marc SAPOVAL, PD, PhD 00 33 (1) 56 09 37 40 marc.sapoval2@egp.aphp.fr

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator:

Guillaume Bobrie, MD

HTA department

More Information

No publications provided

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT01588795 History of Changes
Other Study ID Numbers:	P110122
Study First Received:	April 18, 2012
Last Updated:	June 4, 2012
Health Authority:	France: Committee for the Protection of Personnes

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Diabetic nephropathy
renal denervation
nephroprotection

Renal failure
Renal injury
End stage renal disease

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2
Diabetic Nephropathies
Kidney Diseases
Proteinuria
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications
Urination Disorders
Urological Manifestations
Signs and Symptoms

Cholecalciferol
Vitamin D
Vitamins
Diuretics
Angiotensin Receptor Antagonists
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Natriuretic Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013

Renal Denervation in Diabetic Nephropathy (DERENEDIAB)