Remote Ischemic Preconditioning to Prevent Contrast-Induced Kidney Injury in Diabetic Patients (PRINCES)

NCT ID: NCT07179874

Last Updated: 2025-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-25
• Study Completion Date: 2017-01-09

Brief Summary

This study investigates whether remote ischemic preconditioning (RIPC)-a non-invasive technique involving brief cycles of blood flow restriction to the arm-can prevent contrast-induced nephropathy (CIN) in diabetic patients undergoing coronary angiography. Diabetes mellitus increases the risk of CIN due to heightened oxidative stress and disrupted protective cellular signaling.

While previous research suggests that RIPC may activate renal protective mechanisms, its efficacy in diabetic individuals remains controversial, as metabolic and neurovascular alterations may compromise its effect. This randomized trial aims to determine whether RIPC reduces oxidative kidney damage and improves renal outcomes in this high-risk population. The study will also explore the biological basis for potential variability in response, focusing on oxidative stress biomarkers and early kidney injury indicators.

Detailed Description

This clinical trial explores a non-invasive method known as Remote Ischemic Preconditioning (RIPC) to prevent contrast-induced kidney damage in people with diabetes who are undergoing coronary catheterization. RIPC involves applying brief cycles of restricted blood flow to the arm using a pressure cuff before a medical procedure. Research suggests that RIPC may trigger protective biological responses in distant organs, such as the kidneys, by activating endogenous defense mechanisms including the antioxidant enzyme heme oxygenase-1 (HO-1), and modulation of inflammatory pathways.

The study focuses on a serious complication called Contrast-Induced Nephropathy (CIN)-an acute kidney injury that can occur in patients exposed to contrast dye during medical imaging. CIN is particularly common and severe among individuals with diabetes mellitus and impaired renal function. In this population, the incidence of CIN may reach up to 90%, leading to adverse clinical outcomes and increased healthcare costs.

One major mechanism implicated in CIN is oxidative stress, a state in which excess reactive oxygen species (ROS) overwhelm the body's antioxidant defenses. This imbalance is even more pronounced in diabetic kidneys, where chronic metabolic dysregulation and endothelial dysfunction contribute to heightened susceptibility.

Although early evidence pointed toward a protective role of RIPC against CIN, growing data suggest that its efficacy may be compromised in diabetic individuals. Diabetes-related impairments-including disrupted intracellular signaling, reduced humoral mediator release, autonomic dysfunction, and increased oxidative stress-could attenuate the protective cascade activated by RIPC. Furthermore, peripheral neuropathy, a common complication affecting up to 50% of diabetic patients, may interfere with the neural transmission necessary for systemic RIPC effects.

Nonetheless, clinical studies such as the RenPro Trial have reported preserved RIPC-mediated protection in diabetic populations undergoing contrast exposure. These divergent findings raise important questions about patient-specific factors-including glycemic control, pharmacotherapy, and comorbid conditions-that may modulate the efficacy of this intervention.

The present study was initially designed to evaluate the protective potential of RIPC in the diabetic population. However, from its inception, the trial also considered the hypothesis that protective mechanisms may be altered or suppressed in diabetes. As such, it aims not only to assess clinical outcomes, but also to explore biological indicators that might explain variability in response.

This randomized, parallel-group trial will be conducted in the intensive care unit (ICU) at Hospital General Universitario Santa Lucía. Participants will include adults with diabetes admitted for acute coronary syndrome and scheduled for coronary angiography. Subjects will be randomly assigned to:

• RIPC + hydration group
• Hydration-only control group All participants will receive standard intravenous fluid therapy before and after contrast administration. Those in the RIPC group will undergo four cycles of cuff-induced limb ischemia and reperfusion immediately prior to the procedure.

Biological samples (blood and urine) will be collected at baseline, 24h, 48h, and 72h after contrast exposure to evaluate:

• Traditional kidney function markers: serum creatinine
• Early kidney injury biomarkers: cystatin C.
• Oxidative stress markers: MDA, HO-1 (plasma, urine, and intracellular)

Secondary outcomes include:

• Duration of ICU and hospital stay
• In-hospital mortality
• Correlation between biomarker profiles and prognosis Laboratory analyses will include ELISA and Western blot techniques, while statistical modeling will assess predictive factors and treatment effects.

This study aims to clarify whether RIPC can offer a reproducible, low-cost strategy to prevent CIN in a high-risk diabetic population, and to deepen understanding of the cellular and systemic mechanisms underpinning renal protection under metabolic stress.

Conditions

Contrast-induced Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Remote ischemyc preconditioning.

Participants assigned to this arm received:

• Standard hydration therapy: intravenous infusion of 0.9% saline at 1 ml/kg/h for 12 hours before and after coronary catheterization
• Plus the RIPC procedure: four alternating cycles of upper-arm ischemia (inflating a blood pressure cuff 50 mmHg above systolic pressure for 5 minutes, followed by 5 minutes of reperfusion) performed approximately 45 minutes before catheterization This group was intended to assess the protective renal effects of RIPC in diabetic patients undergoing exposure to intravenous contrast media.

Group Type: EXPERIMENTAL

Remote Ischemic Preconditioning

Intervention Type: PROCEDURE

This intervention involves a non-invasive, mechanical stimulus applied to an upper limb with the goal of activating systemic protective pathways against contrast-induced nephropathy in diabetic patients. Unlike pharmacologic or device-based interventions, RIPC:

• Does not involve any drugs, biologics, or implants
• Is performed using a standard blood pressure cuff, inflated to 50 mmHg above systolic pressure, specifically designed to induce repetitive transient limb ischemia
• Consists of four alternating cycles of 5 minutes inflation followed by 5 minutes reperfusion
• Is applied 45 minutes before coronary catheterization, timed to optimize systemic renal protection prior to exposure to contrast media
• Targets activation of the heme oxygenase-1 (HO-1) enzymatic pathway, linking limb ischemia with antioxidant renal defense mechanisms Unlike interventions that rely solely on hydration or pharmacological antioxidants, this approach seeks to prime endogenous protective systems through is

Control Arm-NO RIPC

Participants in the control arm receive standard care without remote ischemic preconditioning (RIPC). All patients undergo intravenous hydration as part of standard preventive measures prior to coronary catheterization.

• Intervention: 0.9% saline solution administered intravenously at a rate of 1 ml/kg/hour
• Timing: Initiated 12 hours before the procedure and maintained for 12 hours afterward
• Additional Notes: No cuff inflation or ischemic maneuvers are performed. Patients do not receive sham stimulation or any form of simulated ischemia. This arm reflects usual clinical practice in patients undergoing catheterization who meet inclusion criteria.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Remote Ischemic Preconditioning

This intervention involves a non-invasive, mechanical stimulus applied to an upper limb with the goal of activating systemic protective pathways against contrast-induced nephropathy in diabetic patients. Unlike pharmacologic or device-based interventions, RIPC:

• Does not involve any drugs, biologics, or implants
• Is performed using a standard blood pressure cuff, inflated to 50 mmHg above systolic pressure, specifically designed to induce repetitive transient limb ischemia
• Consists of four alternating cycles of 5 minutes inflation followed by 5 minutes reperfusion
• Is applied 45 minutes before coronary catheterization, timed to optimize systemic renal protection prior to exposure to contrast media
• Targets activation of the heme oxygenase-1 (HO-1) enzymatic pathway, linking limb ischemia with antioxidant renal defense mechanisms Unlike interventions that rely solely on hydration or pharmacological antioxidants, this approach seeks to prime endogenous protective systems through is

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Patient diagnosed with diabetes mellitus.
• Age above 18 years.
• Admission to the ICU due to acute coronary syndrome.
• Indication for undergoing a coronary arteriography (either urgent or scheduled)
• Patients who received a coronary arteriography within the last 72 hours (if previously recruited, counted as new for randomization).
• Possibility to perform the RIPC maneuver without delaying the catheterization

Exclusion Criteria

• Absence of diabetes mellitus.
• Pregnant women.
• Renal transplant recipients.
• Patients who underwent urological procedures or received intravenous contrast within the last 72 hours.
• Diagnosis of end-stage renal disease requiring hemodialysis.
• Participation in another clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital General Universitario Santa Lucía

OTHER

Sponsor Role: collaborator

Universidad de Murcia

OTHER

Sponsor Role: lead

Responsible Party

Francisca Rodriguez Mulero

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

FRANCISCA RODRIGUEZ, Ph.D

Role: PRINCIPAL_INVESTIGATOR

University of Murcia-MURCIA

MARIA DOLORES RODRIGUEZ, M.D. Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Hospital Santa Lucía-CARTAGENA, MURCIA

MARIA GALINDO MARTINEZ, M.D. Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Hospital Santa Lucía-CARTAGENA, MURCIA

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Tl14-13 MGM

Identifier Type: -

Identifier Source: org_study_id