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Renal Denervation in Diabetic Nephropathy (DERENEDIAB)

Primary Purpose

Diabetic Nephropathy, Persistent Proteinuria With Type II Diabetes

Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Percutaneous renal denervation and TMNS
Standardized antiproteinuric medication regimen includes an angiotensin receptor blocker , a diuretic , 25OH vitamin D3 and a statin
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Nephropathy focused on measuring Diabetic nephropathy, renal denervation, nephroprotection, Renal failure, Renal injury, End stage renal disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CIC Hopital europeen george pompidou

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Denervation + TMNS

TMNS

Arm Description

Patients are treated with the renal denervation procedure after randomization and are maintained on standardized anti-proteinuric medications

Patients are maintained on standardized anti-proteinuric medications

Outcomes

Primary Outcome Measures

proteinuria/creatininuria ratio

Secondary Outcome Measures

Number of patients with a decrease of the PU/CrU >50% ratio
Evaluation of the slope of decay of the PU/CrU
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
Outcome of the GFR assessed by 51Cr-EDTA clearance
Only in the experimental arm
Decrease of the blood pressure assessed on ABPM
Anti-hypertensive regimen score
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 <
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
Evaluate the outcome of biological parameters
eGFR (MDRD formula), proteinuria/creatininuria ratio
Evaluate the diabetic neuropathy/dysautonomy
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
in the experimental group:urinary levels of KIM1 and NGAL before and 1 year after the denervation

Full Information

First Posted
April 18, 2012
Last Updated
May 30, 2016
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT01588795
Brief Title
Renal Denervation in Diabetic Nephropathy
Acronym
DERENEDIAB
Official Title
Renal Denervation in Patients With Diabetic Nephropathy and Persistent Proteinuria
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Nephropathy, Persistent Proteinuria With Type II Diabetes
Keywords
Diabetic nephropathy, renal denervation, nephroprotection, Renal failure, Renal injury, End stage renal disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Denervation + TMNS
Arm Type
Experimental
Arm Description
Patients are treated with the renal denervation procedure after randomization and are maintained on standardized anti-proteinuric medications
Arm Title
TMNS
Arm Type
Active Comparator
Arm Description
Patients are maintained on standardized anti-proteinuric medications
Intervention Type
Procedure
Intervention Name(s)
Percutaneous renal denervation and TMNS
Intervention Description
Patients are treated with the renal denervation procedure after randomization and are maintained on standardized anti-proteinuric medications
Intervention Type
Drug
Intervention Name(s)
Standardized antiproteinuric medication regimen includes an angiotensin receptor blocker , a diuretic , 25OH vitamin D3 and a statin
Intervention Description
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)
Primary Outcome Measure Information:
Title
proteinuria/creatininuria ratio
Time Frame
from baseline to 1 year
Secondary Outcome Measure Information:
Title
Number of patients with a decrease of the PU/CrU >50% ratio
Time Frame
from baseline to 1 year
Title
Evaluation of the slope of decay of the PU/CrU
Time Frame
from baseline to 1 year
Title
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
Description
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
Title
Outcome of the GFR assessed by 51Cr-EDTA clearance
Description
Only in the experimental arm
Time Frame
from randomisation to 1 year
Title
Decrease of the blood pressure assessed on ABPM
Time Frame
From randomisation to 1 year
Title
Anti-hypertensive regimen score
Time Frame
from baseline to 1 year
Title
Evaluation of the renal arterial anatomy
Description
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 <
Time Frame
from baseline to 1 year
Title
Evaluation of safety and tolerance of renal denervation in diabetic patients with overt proteinuria
Description
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
Time Frame
from baseline to 1 year
Title
Evaluate the outcome of biological parameters
Description
eGFR (MDRD formula), proteinuria/creatininuria ratio
Time Frame
from baseline to 1 year
Title
Evaluate the diabetic neuropathy/dysautonomy
Description
in the experimental:blood pressure in orthostatism, pulse wave velocimetry, RR interval on the Holter ECG, cutaneous baroreflex
Time Frame
from randomisation to 1 year
Title
Evaluate the outcome of specific kidney injury markers
Description
in the experimental group:urinary levels of KIM1 and NGAL before and 1 year after the denervation
Time Frame
from randomisation to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guillaume Bobrie, MD
Organizational Affiliation
HTA department
Official's Role
Principal Investigator
Facility Information:
Facility Name
CIC Hopital europeen george pompidou
City
Paris
ZIP/Postal Code
75015
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
25186534
Citation
Persu A, Sapoval M, Azizi M, Monge M, Danse E, Hammer F, Renkin J. Renal artery stenosis following renal denervation: a matter of concern. J Hypertens. 2014 Oct;32(10):2101-5. doi: 10.1097/HJH.0000000000000323. No abstract available.
Results Reference
derived

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Renal Denervation in Diabetic Nephropathy

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