Ciclosporin A Preconditioning for Renal Artery Stenosis

Renal Artery Stenosis Clinical Trial

— CicloSAAR  

Official title:

Impact of a Ciclosporin A Preconditioning for Prevention of Ischemia-reperfusion Injury After Renal Artery Stenosis Dilation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03382301
• Other study ID #: 69HCL16_0823
• Secondary ID: 2017-002937-48
• Status: Completed
• Phase: Phase 2
• Start date: August 28, 2018
• Est. completion date: June 18, 2020

Study information

• Verified date: May 2024
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: June 18, 2020
• Est. primary completion date: June 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Constriction, Pathologic
• Renal Artery Obstruction
• Renal Artery Stenosis
• Reperfusion Injury

Intervention

Drug:
• Ciclosporin A preconditioning before renal artery stenosis dilation
Ciclosporin A perfusion (2.5 mg/kg) for 1 hour before renal artery dilation
• NaCl preconditioning before renal artery stenosis dilation
NaCl perfusion (Saline perfusion) for 1 hour (2.5 mg/kg) before renal artery dilation

Locations

Country	Name	City	State
France	Service d'Exploration Fonctionnelle Rénale, Hôpital Edouard Herriot, Hospices Civils de Lyon	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in relative increase (baseline and 3 months after) of global renal perfusion between the two groups	Global renal perfusion is assessed by 15O labeled water PET (Positron Emission Tomography) imaging	3 months after renal artery stenosis dilation
Secondary	Difference in the relative increase (baseline and 3 months after) of global renal oxidative metabolism between the two groups	Global renal oxidative metabolism is assessed by 11C labeled acetate PET (Positron Emission Tomography) imaging	3 months after renal artery stenosis dilation
Secondary	Difference in the relative increase (baseline and 3 months after) of global renal oxygen content between the two groups	Global renal oxygen content is assessed by BOLD MRI (Blood-Oxygen-Level Dependent Magnetic Resonance Imaging)	3 months after renal artery stenosis dilation
Secondary	Difference in the relative increase (baseline and 3 months after) of global glomerular filtration rate between the two groups	Global glomerular filtration rate is assessed by Iohexol measured clearance	3 months after renal artery stenosis dilation
Secondary	Difference in the relative increase (baseline and 3 months after) of single-kidney perfusion (ischemic versus contralateral kidney) between the two groups	Kidney perfusion is assessed by 15O labeled water PET (Positron Emission Tomography) imaging	3 months after renal artery stenosis dilation