Clinical trial NCT01588795: Renal Denervation in Diabetic Nephropathy
Official title: Renal Denervation in Patients With Diabetic Nephropathy and Persistent Proteinuria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Nephropathy
Persistent Proteinuria With Type II Diabetes
Keywords: Diabetic nephropathy
renal denervation
nephroprotection
Renal failure
Renal injury
End stage renal disease
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2012-05-01
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: proteinuria/creatininuria ratio
timeFrame: from baseline to 1 year
Secondary outcomes:
measure: Number of patients with a decrease of the PU/CrU >50% ratio
timeFrame: from baseline to 1 year
measure: Evaluation of the slope of decay of the PU/CrU
timeFrame: from baseline to 1 year
measure: 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
timeFrame: from baseline to 1 year
measure: Outcome of the GFR assessed by 51Cr-EDTA clearance
timeFrame: from randomisation to 1 year
measure: Decrease of the blood pressure assessed on ABPM
timeFrame: From randomisation to 1 year
measure: Anti-hypertensive regimen score
timeFrame: from baseline to 1 year
measure: Evaluation of the renal arterial anatomy
timeFrame: from baseline to 1 year
measure: Evaluation of safety and tolerance of renal denervation in diabetic patients with overt proteinuria
timeFrame: from baseline to 1 year
measure: Evaluate the outcome of biological parameters
timeFrame: from baseline to 1 year
measure: Evaluate the diabetic neuropathy/dysautonomy
timeFrame: from randomisation to 1 year
measure: Evaluate the outcome of specific kidney injury markers
timeFrame: from randomisation to 1 year
Other outcomes:
Locations:
city: Paris
country: France
facility: CIC Hopital europeen george pompidou
Study officials:
affiliation: HTA department
name: Guillaume Bobrie, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.