Chronic Renal FailureGenderBOLDNCT04085094
Gender Differences in Renal Functioning and Disease
An observational study of Chronic Renal Failure and Healthy Controls, run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic Renal Failure, Healthy Controls
- What is being tested?
- high-salt diet (V1) and low salt diet (V2), Contrast-enhanced ultrasound (CEUS) and functional MRI
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 98 participants
- Where
- 1 siteSwitzerland
- Study dates
- 30 May 2017to 2 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy volunteers will be recruited by way of advertisement at CHUV. Patients with CKD will be recruited via the ambulatory nephrology consultation.
Who may be able to join
- 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.
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- 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.
- 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.
- 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.
Who cannot join
- Contra-indication for Magnetic Resonance Imaging (Pacemaker, implanted metallic device, claustrophobia,..)
- Known allergy to one of the study compounds (furosemide, Sonovue).
- Autosomal dominant polycystic kidney disease.
- Ingestion of corticosteroids or other immunosuppressants.
- Volume overload or heart failure.
- eGFR < 15ml/min/1.73m2 or dialysis.
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Gender Differences in Renal Disease Progression: an Analysis of Potential Mechanisms Using Modern Radiological Techniques
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.
Read the detailed 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.
- Conditions
- Chronic Renal Failure, Healthy Controls
- Being tested
- high-salt diet (V1) and low salt diet (V2), Contrast-enhanced ultrasound (CEUS), functional MRI, Pilocarpine test
- Keywords
- BOLD-MRI, Contrast-enhanced ultrasound (CEUS), Salt storage, Perfusion index, Resistance index, Renal functional reserve, Renal oxygenation
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
high-salt diet (V1) and low salt diet (V2)Dietary supplement
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.
Contrast-enhanced ultrasound (CEUS)Diagnostic test
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 MRIDiagnostic test
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.
Pilocarpine testOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 1. Healthy and pre-menopausal women without CKD | A total of 45 healthy and pre-menopausal women (<50 years old) will be recruited. Thirty of them are not on oral anticonception; 15 will be examined at each visit during their follicular phase, 15 during their luteal phase. Fifteen are on oral contraception.
Three visits will take place:
* V1: after 5 days of a high salt diet (adding 6g of salt/day on top of regular diet), patients will undergo renal ultrasound (Doppler and CEUS), renal functional MRI (BOLD and phase contrast) and Na23 muscle and skin MRI.
* V2: after 5 days of low salt diet (dietary instructions), the same exams mentioned above will be repeated
* V3: renal CEUS will be performed before and after an oral protein load (1g/kg) or after SL nitroglycerin (0.2mg).
The day before each visit, a 24h urine collection will be performed in order to measure renal salt excretion. Receives: Dietary Supplement: high-salt diet (V1) and low salt diet (V2); Diagnostic Test: Contrast-enhanced ultrasound (CEUS); Diagnostic Test: functional MRI; Other: Pilocarpine test | |
| 2. Pre-menopausal women with CKD | A total of 30 women with CKD will be recruited and undergo the same visits as outlined above Receives: Dietary Supplement: high-salt diet (V1) and low salt diet (V2); Diagnostic Test: Contrast-enhanced ultrasound (CEUS); Diagnostic Test: functional MRI | |
| 3. Post-menopausal women without CKD | Fifteen post-menopausal women will undergo the same exams as outlined above Receives: Dietary Supplement: high-salt diet (V1) and low salt diet (V2); Diagnostic Test: Contrast-enhanced ultrasound (CEUS); Diagnostic Test: functional MRI | |
| 4. Healthy men | A total of thirty age-and sex-matched men (15 below and 15 above 50 years old) will undergo the same exams as above. Receives: Dietary Supplement: high-salt diet (V1) and low salt diet (V2); Diagnostic Test: Contrast-enhanced ultrasound (CEUS); Diagnostic Test: functional MRI; Other: Pilocarpine test | |
| 5.Men with CKD | Fifteen men with CKD will undergo the same exams as outlined above Receives: Diagnostic Test: Contrast-enhanced ultrasound (CEUS); Diagnostic Test: functional MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in renal microperfusion according to dietary salt intake in healthy and CKD
Renal perfusion is measured with the contrast-enhanced ultrasound (CEUS)
Measured: 1 month (5 days high salt- two weeks wash out- 5 days low salt)
Change in renal oxygenation after salty/unsalted diets in women compared to men
Renal oxygenation is measured by Blood Oxygen Level Dependent (BOLD-IRM)
Measured: 1 month
Change in skin and muscle storage of sodium according to salt intake
Changes in cutaneous and muscle sodium storage measured by 23Na-MRI
Measured: 1 month
Change in renal perfusion measured with CEUS after SL nitroglycerine
Renal perfusion is measured with the contrast-enhanced ultrasound (CEUS)
Measured: before-5 minutes after NTG
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2019
- Study start30 May 2017
- Primary completion2 Dec 2019
- Study completion2 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Renal FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Vaudois
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Geneva
- Responsible party
- Principal investigator, Gregoire Wuerzner; MD, Centre Hospitalier Universitaire Vaudois
- Investigators
- Menno Pruijm, PD MD, Principal investigator, CHUV
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04085094
- Sponsor's protocol ID
- 2016-01971
- Other IDs
- 2016
- Acronym
- GenderBOLD
- Status last verified
- Sep 2023
- First submitted
- 9 Sep 2019
- Last updated
- 13 Sep 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gender Differences in Renal Disease Progression: an Analysis of Potential Mechanisms Using Modern Radiological Techniques
- ClinicalTrials.gov ID
- NCT04085094
- Acronym / sponsor ID
- GenderBOLD / 2016-01971
- Conditions
- Chronic Renal Failure, Healthy Controls
- Keywords
- BOLD-MRI, Contrast-enhanced ultrasound (CEUS), Salt storage, Perfusion index, Resistance index, Renal functional reserve, Renal oxygenation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire VaudoisUniversity, hospital or other
- Collaborators
- University Hospital, Geneva
- Study start
- 30 May 2017 (actual)
- Primary completion
- 2 Dec 2019 (actual)
- Study completion
- 2 Dec 2019 (actual)
- First posted
- 11 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1. Healthy and pre-menopausal women without CKD | – | Dietary Supplement: high-salt diet (V1) and low salt diet (V2), Diagnostic Test: Contrast-enhanced ultrasound (CEUS), Diagnostic Test: functional MRI, Other: Pilocarpine testA total of 45 healthy and pre-menopausal women (<50 years old) will be recruited. Thirty of them are not on oral anticonception; 15 will be examined at each visit during their follicular phase, 15 during their luteal phase. Fifteen are on oral contraception. Three visits will take place: * V1: after 5 days of a high salt diet (adding 6g of salt/day on top of regular diet), patients will undergo renal ultrasound (Doppler and CEUS), renal functional MRI (BOLD and phase contrast) and Na23 muscle and skin MRI. * V2: after 5 days of low salt diet (dietary instructions), the same exams mentioned above will be repeated * V3: renal CEUS will be performed before and after an oral protein load (1g/kg) or after SL nitroglycerin (0.2mg). The day before each visit, a 24h urine collection will be performed in order to measure renal salt excretion. |
| 2. Pre-menopausal women with CKD | – | Dietary Supplement: high-salt diet (V1) and low salt diet (V2), Diagnostic Test: Contrast-enhanced ultrasound (CEUS), Diagnostic Test: functional MRIA total of 30 women with CKD will be recruited and undergo the same visits as outlined above |
| 3. Post-menopausal women without CKD | – | Dietary Supplement: high-salt diet (V1) and low salt diet (V2), Diagnostic Test: Contrast-enhanced ultrasound (CEUS), Diagnostic Test: functional MRIFifteen post-menopausal women will undergo the same exams as outlined above |
| 4. Healthy men | – | Dietary Supplement: high-salt diet (V1) and low salt diet (V2), Diagnostic Test: Contrast-enhanced ultrasound (CEUS), Diagnostic Test: functional MRI, Other: Pilocarpine testA total of thirty age-and sex-matched men (15 below and 15 above 50 years old) will undergo the same exams as above. |
| 5.Men with CKD | – | Diagnostic Test: Contrast-enhanced ultrasound (CEUS), Diagnostic Test: functional MRIFifteen men with CKD will undergo the same exams as outlined above |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy volunteers will be recruited by way of advertisement at CHUV. Patients with CKD will be recruited via the ambulatory nephrology consultation.
Key inclusion criteria (25 listed)
- 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.
Key exclusion criteria (10 listed)
- Contra-indication for Magnetic Resonance Imaging (Pacemaker, implanted metallic device, claustrophobia,..)
- Known allergy to one of the study compounds (furosemide, Sonovue).
- Autosomal dominant polycystic kidney disease.
- Ingestion of corticosteroids or other immunosuppressants.
- Volume overload or heart failure.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Dietary supplement | 1. Healthy and pre-menopausal women without CKD, 2. Pre-menopausal women with CKD, 3. Post-menopausal women without CKD, 4. Healthy men |
| 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. | Diagnostic test | 1. Healthy and pre-menopausal women without CKD, 2. Pre-menopausal women with CKD, 3. Post-menopausal women without CKD, 4. Healthy men, 5.Men with CKD |
| functional MRIMeasurement 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. | Diagnostic test | 1. Healthy and pre-menopausal women without CKD, 2. Pre-menopausal women with CKD, 3. Post-menopausal women without CKD, 4. Healthy men, 5.Men with CKD |
| Pilocarpine testAssessment 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. | Other | 1. Healthy and pre-menopausal women without CKD, 4. Healthy men |
Primary outcome
Change in renal microperfusion according to dietary salt intake in healthy and CKD
Time frame: 1 month (5 days high salt- two weeks wash out- 5 days low salt)
Renal perfusion is measured with the contrast-enhanced ultrasound (CEUS)
Change in renal oxygenation after salty/unsalted diets in women compared to men
Time frame: 1 month
Renal oxygenation is measured by Blood Oxygen Level Dependent (BOLD-IRM)
Change in skin and muscle storage of sodium according to salt intake
Time frame: 1 month
Changes in cutaneous and muscle sodium storage measured by 23Na-MRI
Change in renal perfusion measured with CEUS after SL nitroglycerine
Time frame: before-5 minutes after NTG
Renal perfusion is measured with the contrast-enhanced ultrasound (CEUS)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Menno Pruijm, PD MD principal investigator
CHUV
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Renal Failure and Healthy Controls, run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in renal microperfusion according to dietary salt intake in healthy and CKD (time frame: 1 month (5 days high salt- two weeks wash out- 5 days low salt)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.