Ciclosporin A Preconditioning for Renal Artery Stenosis

NCT03382301 | Completed Phase 2 DMC

• 2 other identifiers: 69HCL16_08232017-002937-48
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Renal Artery Stenosis

Keywords

Ischemia reperfusion injuries; Renal artery stenosis; Renal functional imaging

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Difference in the relative increase (baseline and 3 months after) of global renal oxidative metabolism between the two groups

  3 months after renal artery stenosis dilation

• Difference in the relative increase (baseline and 3 months after) of global renal oxygen content between the two groups

  3 months after renal artery stenosis dilation

• Difference in the relative increase (baseline and 3 months after) of global glomerular filtration rate between the two groups

  3 months after renal artery stenosis dilation

• Difference in the relative increase (baseline and 3 months after) of single-kidney perfusion (ischemic versus contralateral kidney) between the two groups

  3 months after renal artery stenosis dilation

Study Arms (2)

Ciclosporin A preconditioning

EXPERIMENTAL

Ciclosporin A preconditioning before renal artery stenosis dilation

Drug: Ciclosporin A preconditioning before renal artery stenosis dilation

NaCl preconditioning

PLACEBO COMPARATOR

Drug: NaCl preconditioning before renal artery stenosis dilation

Interventions

Ciclosporin A preconditioning before renal artery stenosis dilation DRUG

Ciclosporin A perfusion (2.5 mg/kg) for 1 hour before renal artery dilation

Ciclosporin A preconditioning

NaCl preconditioning before renal artery stenosis dilation DRUG

NaCl perfusion (Saline perfusion) for 1 hour (2.5 mg/kg) before renal artery dilation

NaCl preconditioning

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• MRI contra indications (MRI incompatible pacemaker or insulin pomp, metal clip, MRI incompatible cardiac valve, dental brace, claustrophobia)

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Service d'Exploration Fonctionnelle Rénale, Hôpital Edouard Herriot, Hospices Civils de Lyon

Lyon, 69437, France

Location

MeSH Terms

Conditions

Renal Artery Obstruction; Reperfusion Injury

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: December 22, 2017
• Study Start: August 28, 2018
• Primary Completion: June 18, 2020
• Study Completion: June 18, 2020
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

FR (1)