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Ciclosporin A Preconditioning for Renal Artery Stenosis (CicloSAAR)

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ClinicalTrials.gov Identifier: NCT03382301
Recruitment Status : Recruiting
First Posted : December 22, 2017
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

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.


Condition or disease Intervention/treatment Phase
Renal Artery Stenosis Drug: Ciclosporin A preconditioning before renal artery stenosis dilation Drug: NaCl preconditioning before renal artery stenosis dilation Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Impact of a Ciclosporin A Preconditioning for Prevention of Ischemia-reperfusion Injury After Renal Artery Stenosis Dilation
Actual Study Start Date : August 28, 2018
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ciclosporin A preconditioning
Ciclosporin A preconditioning before renal artery stenosis dilation
Drug: Ciclosporin A preconditioning before renal artery stenosis dilation
Ciclosporin A perfusion (2.5 mg/kg) for 1 hour before renal artery dilation

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




Primary Outcome Measures :
  1. Difference in relative increase (baseline and 3 months after) of global renal perfusion between the two groups [ Time Frame: 3 months after renal artery stenosis dilation ]
    Global renal perfusion is assessed by 15O labeled water PET (Positron Emission Tomography) imaging


Secondary Outcome Measures :
  1. Difference in the relative increase (baseline and 3 months after) of global renal oxidative metabolism between the two groups [ Time Frame: 3 months after renal artery stenosis dilation ]
    Global renal oxidative metabolism is assessed by 11C labeled acetate PET (Positron Emission Tomography) imaging

  2. Difference in the relative increase (baseline and 3 months after) of global renal oxygen content between the two groups [ Time Frame: 3 months after renal artery stenosis dilation ]
    Global renal oxygen content is assessed by BOLD MRI (Blood-Oxygen-Level Dependent Magnetic Resonance Imaging)

  3. Difference in the relative increase (baseline and 3 months after) of global glomerular filtration rate between the two groups [ Time Frame: 3 months after renal artery stenosis dilation ]
    Global glomerular filtration rate is assessed by Iohexol measured clearance

  4. Difference in the relative increase (baseline and 3 months after) of single-kidney perfusion (ischemic versus contralateral kidney) between the two groups [ Time Frame: 3 months after renal artery stenosis dilation ]
    Kidney perfusion is assessed by 15O labeled water PET (Positron Emission Tomography) imaging



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 1 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03382301


Contacts
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Contact: Sandrine LEMOINE, MD 472 110 263 ext +33 Sandrine.lemoine01@chu-lyon.fr
Contact: Gabrielle Laetitia NORMAND, MD 472 110 263 ext +33 laetitia.normand@chu-lyon.fr

Locations
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France
Service d'Exploration Fonctionnelle Rénale, Hôpital Edouard Herriot, Hospices Civils de Lyon Recruiting
Lyon, France, 69437
Contact: Sandrine LEMOINE, MD    472 110 263 ext +33    Sandrine.lemoine01@chu-lyon.fr   
Contact: Gabrielle Laetitia NORMAND, MD    472 110 263 ext +33    laetitia.normand@chu-lyon.fr   
Principal Investigator: Sandrine LEMOINE, MD         
Sponsors and Collaborators
Hospices Civils de Lyon

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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT03382301     History of Changes
Other Study ID Numbers: 69HCL16_0823
First Posted: December 22, 2017    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospices Civils de Lyon:
Ischemia reperfusion injuries
Renal artery stenosis
Renal functional imaging
Additional relevant MeSH terms:
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Renal Artery Obstruction
Kidney Diseases
Reperfusion Injury
Constriction, Pathologic
Pathological Conditions, Anatomical
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Pathologic Processes
Urologic Diseases
Arterial Occlusive Diseases
Cyclosporine
Cyclosporins
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors