Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04085094
Other study ID # 2016-01971
Secondary ID
Status Completed
Phase
First received
Last updated
Start date May 30, 2017
Est. completion date December 2, 2019

Study information

Verified date September 2023
Source Centre Hospitalier Universitaire Vaudois
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

The purpose of the GenderBOLD study is to shed light on the mechanisms responsible for women's lower susceptibility to developing and progressing chronic renal disease, using modern imaging techniques, and applying different diets. The investigators postulate that oxygenation and renal perfusion are better conserved and change less in women than in men in different dietary situations (high salt-low salt), possibly because they are able to store excess salt in their skin and muscles. The investigators postulate that these differences are independent of their menstrual cycle. Finally, the investigators will analyze the renal functional reserve and changes in renal perfusion through an oral protein load and after sublingual nitroglycerin to assess whether potential différences exist between genders.


Description:

Chronic kidney disease (CKD) affects about 10% of the adult population in Switzerland. Despite decades of research, the mechanisms involved in the development and progression of CKD remain unclear, and there is a lack of preventative therapies. Women are relatively protected against CKD, but this topic has been little studied. The kidney is very sensitive to hypoxia and its chronic oxygen depravation is the final step in the pathogenesis of CKD. A special MRI application, called BOLD-MRI, has the ability to measure renal tissue oxygenation in humans. In a recent BOLD-MRI study, the investigators demonstrated that cortical oxygenation is significantly higher in women than in men, which may explain women's lower susceptibility to declining renal function. However, whether this is true under different dietary conditions (high salt-low salt), and whether renal oxygenation changes throughout the menstrual cycle is unknown and will be assessed in this study. Renal oxygenation depends on its perfusion. Renal micro-perfusion can be measured with contrast-enhanced ultrasound (CEUS) and is expressed as PI (perfusion index). CEUS is a recent imaging technique that combines conventional ultrasound with the administration of a microbubble contrast agent (a lipid or albumin-enveloped gas compound). The microbubbles are inert and eliminated by pulmonary and hepatic systems within one hour of administration. They are not nephrotoxic and have no major side effects. Whether there are differences in renal perfusion as measured with CEUS between men and women with and without CKD will be also assessed in this study. Oxygenation of the kidneys does not only depend on their perfusion, but also on their consumption, mainly related to tubular active sodium transport. Thus, their oxygenation is lower in the case of a high salt diet compared to a low salt diet. This has been proven in men, but not in women. Recently, another MRI technique called 23Na MRI was used to measure the amount of salt stored in the skin and muscles. It is possible that the cutaneous and muscular capacity of storing salt according to dietary salt intake is lower in men, but this has not, at present, been examined.


Recruitment information / eligibility

Status Completed
Enrollment 98
Est. completion date December 2, 2019
Est. primary completion date December 2, 2019
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years and older
Eligibility Inclusion/exclusion Criteria: Inclusion criteria for healthy pre-menopausal women: - Age = 18 years old and <50 years old. - No drugs (psychoactive substances used for non-medical purposes) /medicine. - Blood pressure <135/85mmHg. - Renal function (eGFR >90ml/min/1.73m2) and absence of albuminuria. - Regular menstrual cycle. - No pregnancy. - Understanding and signature of the informed consent. Inclusion criteria for pre-menopausal women with a chronic renal failure: - Age = 18 years old and <50 years old. - Possibility to stop the treatment during the day of the study. - Reduced renal function (eGFR 15-60 ml/min/1.73m2) or eGFR 60-90 ml/min/1.73m2 with the presence of albuminuria >300 mg/j. - Understanding and signature of the informed consent. Inclusion criteria for post-menopausal women: - Age = 50 years old. - Absence of menstruation. - No drugs consumption. - No medicine, or possibility to stop it two days before the study. - Blood pressure <135/85mmHg. - Renal function (eGFR >90ml/min/1.73m2) and absence of albuminuria. - Understanding and signature of the informed consent. Inclusion criteria for men: - Age = 18 years old, but matched with the age of pre- aor post-menopausal women - No drugs consumption. - No medicine, or possibility to stop it two days before the study. - Blood pressure <135/85mmHg. - Renal function (eGFR >90ml/min/1.73m2) and absence of albuminuria. - Understanding and signature of the informed consent. Exclusion criteria for all: - Contra-indication for Magnetic Resonance Imaging (Pacemaker, implanted metallic device, claustrophobia,..) - Known allergy to one of the study compounds (furosemide, Sonovue). Exclusion criteria for persons with chronic renal failure: - Autosomal dominant polycystic kidney disease. - Ingestion of corticosteroids or other immunosuppressants. - Volume overload or heart failure. - eGFR < 15ml/min/1.73m2 or dialysis. Exclusion criteria for men and women receiving sublingual nitroglycerin: - Hypersensitivity to nitrous derivatives or to one of the excipients present in the composition. - History of heart disease (ischemic heart disease, valve and/or rhythmic). - Low blood pressure (systolic blood pressure <100mmHg)

Study Design


Intervention

Dietary Supplement:
high-salt diet (V1) and low salt diet (V2)
Before the first visit, the participant will follow a five-day high salt diet (addition of 6g/day of salt to their regular diet followed at home). Before the second visit (V2), the participant will follow for five days a low-salt diet, according to dietary instructions followed provided during the screening visit.
Diagnostic Test:
Contrast-enhanced ultrasound (CEUS)
Renal ultrasound with use of a contrast product (SonoVue®), perfusion rate 0.015ml/kg/min. Four destruction-reperfusion sequences are performed in order to measure the Perfusion Index (PI) of the renal cortex.
functional MRI
Measurement of renal oxygenation with the Blood Oxygenation Level Dependant-MRI technique (BOLD-MRI) on Siemens Prisma 3T scanner before and 15minutes after 0.03mg/kg of IV furosemide. Assessment of the amount of salt stored in the skin and muscles with the 23Na MRI technique.
Other:
Pilocarpine test
Assessment of sweat salt and potassium concentrations in healthy volunteers according to slat intake. Two electrodes are placed on the forearm. The electric current between the two electrodes will induce perspiration which will be collected with the Macroduct system.

Locations

Country Name City State
Switzerland CHUV, nephrology service Lausanne Vaud

Sponsors (2)

Lead Sponsor Collaborator
Centre Hospitalier Universitaire Vaudois University Hospital, Geneva

Country where clinical trial is conducted

Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change in renal microperfusion according to dietary salt intake in healthy and CKD Renal perfusion is measured with the contrast-enhanced ultrasound (CEUS) 1 month (5 days high salt- two weeks wash out- 5 days low salt)
Primary Change in renal oxygenation after salty/unsalted diets in women compared to men Renal oxygenation is measured by Blood Oxygen Level Dependent (BOLD-IRM) 1 month
Primary Change in skin and muscle storage of sodium according to salt intake Changes in cutaneous and muscle sodium storage measured by 23Na-MRI 1 month
Primary Change in renal perfusion measured with CEUS after SL nitroglycerine Renal perfusion is measured with the contrast-enhanced ultrasound (CEUS) before-5 minutes after NTG
See also
  Status Clinical Trial Phase
Recruiting NCT02565459 - MSC and Kidney Transplant Tolerance (Phase A) Phase 1
Recruiting NCT02356419 - rESP Medication With a Single Intravenous Administration and Dose Escalation to Explore the Tolerability ,Safety and Pharmacokinetic Characteristics Phase 1
Recruiting NCT01876017 - Safety and Efficacy of BMMNC in Patients With Chronic Renal Failure Phase 1/Phase 2
Withdrawn NCT03019159 - Assessment of a Follow-up With Tele-consulting for Patients With Renal Failure Under Peritoneal Dialysis N/A
Completed NCT02047006 - Dose-finding of Rivaroxaban in Hemodialysis Phase 4
Completed NCT01617824 - Rapid Effects Linagliptin on Monocyte Polarization and Endothelial Progenitor Cells in Type 2 Diabetes Phase 4
Completed NCT00828776 - Pharmacodynamics and Non-Clinical Inferiority of Heparin Sodium (Cristália) Compared With the Product Liquemine (Roche) in Chronic Renal Failure Phase 2/Phase 3
Completed NCT00597753 - Safety & Efficacy of Peginesatide for Maintenance Treatment of Anemia in Participants With Chronic Kidney Disease on Hemodialysis Phase 3
Completed NCT00379899 - ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis Phase 4
Terminated NCT00372489 - Extension Study to Evaluate Safety and Tolerability of Peginesatide for Long-Term Treatment of Anemia in Participants With CKD Phase 2
Completed NCT00228436 - Safety, PD & PK of Multiple Doses of Peginesatide for Anemia in Chronic Kidney Disease Patients Phase 2
Completed NCT03772171 - Estimate for Dietary Intakes and Hemodialysis Patients
Recruiting NCT02586402 - Safety & Efficacy of Pegolsihematide for Treatment of Anemia in Participants on Dialysis Phase 2
Completed NCT01879618 - Use Of Fragmin In Hemodialysis Phase 3
Not yet recruiting NCT01346215 - Study of Clinical Non-inferiority of Actparin® (Laboratorio Bergamo) Compared to Heparin Sodium (APP Pharmaceuticals), in Patients With Chronic Renal Failure Phase 3
Completed NCT01220843 - FGF23 Reduction : Efficacy of a New Phosphate Binder in CHronic Kidney Disease Phase 3
Completed NCT01111630 - Study of Erythropoietin (EPO) Administration Schedule Phase 4
Completed NCT00742716 - Safety Study of CTA018 Injection to Treat Stage 5 Chronic Kidney Disease Phase 2
Completed NCT00598273 - Safety & Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis Phase 3
Completed NCT00597584 - Safety & Efficacy of Peginesatide for Maintenance Treatment of Anemia in Participants With Chronic Kidney Disease on Hemodialysis Phase 3