Renal Denervation in Diabetic Nephropathy (DERENEDIAB)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01588795
First received: April 18, 2012
Last updated: June 5, 2013
Last verified: June 2013
  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:


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 2015
Estimated Primary Completion Date: April 2015 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 5, 2013
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:
Diabetic Nephropathies
Kidney Diseases
Diabetes Mellitus, Type 2
Proteinuria
Urologic Diseases
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Diabetes Complications
Urination Disorders
Urological Manifestations
Signs and Symptoms
Vitamins
Vitamin D
Cholecalciferol
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 October 01, 2014