Ciclosporin A Preconditioning for Renal Artery Stenosis (CicloSAAR)

Civil Hospices of Lyon

Status and phase

Completed

Phase 2

Conditions

Renal Artery Stenosis

Treatments

Drug: NaCl preconditioning before renal artery stenosis dilation

Drug: Ciclosporin A preconditioning before renal artery stenosis dilation

Study type

Interventional

Funder types

Other

Identifiers

NCT03382301

69HCL16_0823

2017-002937-48 (EudraCT Number)

Details and patient eligibility

About

Renal artery stenosis is one the leading cause of secondary hypertension. Previous randomized controlled trials in humans have failed to demonstrate an improvement of renal function after stenosis dilation, probably because of a selection bias with more severe patients being excluded from randomization. Renal ischemia-reperfusion injuries have also not been taken into account. Indeed, reperfusion leads to a rapid renal blood flow recovery associated with renal ischemia-reperfusion injuries.

Mitochondrial permeability transition pore (mPTP) is a key player in the occurrence of ischemia reperfusion injuries because its opening leads to mitochondria leakage and cell death. However, preconditioning whether pharmacological or ischemic can prevent mPTP opening and protect cells. Ciclosporin A can prolong mPTP closing during reperfusion and reduce renal and cardiac tissular lesions. Another mPTP blocker (Bendavia) has been associated with an improvement of renal blood flow (RBF) and glomerular filtration rate (GFR) after renal artery stenosis dilation at 6 weeks in pigs. Based on a recent study, dilation overall benefit could be secondary to an improvement of the contralateral kidney GFR and tissue oxygen content, requiring a single kidney evaluation of those renal functional parameters. The investigators previously demonstrated that dose and timing of ciclosporin A preconditioning is key to protect kidneys from ischemia-reperfusion injuries. Previous controlled trials that failed to demonstrate a benefit of ciclosporin A conditioning have used post conditioning on necrotic cells. Considering kidney ischemia-reperfusion injuries, preconditioning have led to more encouraging results compared to ciclosporin A post conditioning in animals. Therefore the investigators aim to conduct the first clinical study of ciclosporin A preconditioning for prevention of kidney ischemia-reperfusion injuries after renal artery stenosis dilation.

Using renal functional imaging and the new PET-MRI (Positron Emission Tomography-Magnetic Resonance Imaging) combined device, the investigators will evaluate kidney perfusion, oxidative metabolism, glomerular filtration rate and oxygen content before and 3 months after renal artery stenosis dilation with or without a ciclosporin A preconditioning.

Enrollment

5 patients

Sex

All

Ages

50+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients over 50 years of age
For women : only menopausal women
Estimated Glomerular filtration rate ≥ 25 mL/min/1.73m2
Renal artery stenosis with ≥ 70 % caliber reduction (Doppler or scanner or MRI)
No controlateral stenosis
Kidney size ≥ 7 cm
Only atheromatous renal artery stenosis
Resistant hypertension and/or rapid loss of kidney function and/or flash pulmonary edema
Collective decision of dilation after a multidisciplinary meeting

Exclusion criteria

Inclusion in another study
Protected adults
Person without a social security coverage
Imprisoned person
Systolic blood pressure >180 mmHg and/or diastolic blood pressure > 110 mmHg
Non atheromatous renal artery stenosis
Single kidney
Multiple myeloma
Iodine contrast agents allergy
Ciclosporin A hypersensibility
Severe other medical conditions that could be exacerbated by Iodine injection (cancer, lymphoma, active Hepatitis B, active Hepatitis C, uncontrolled HIV)
Previous radiation exposure (above 20 mSv (millisievert) in the last 6 months before inclusion)
MRI contra indications (MRI incompatible pacemaker or insulin pomp, metal clip, MRI incompatible cardiac valve, dental brace, claustrophobia)