Kidney HypoxiaECSTASYNCT06284785
The Effects of Bariatric Surgery on Kidney Oxygenation in Obese Adults With Type 2 Diabetes and Hyperfiltration
An observational study of Kidney Hypoxia and Diabetes Mellitus, Type 2, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
In this study the investigators will examine the effects of VAT reduction by bariatric surgery on kidney hypoxia and compare kidney oxygenation before- and after surgery in both sexes using BOLD-MRI and measures of kidney hemodynamic function. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Kidney Hypoxia, Diabetes Mellitus, Type 2
- What is being tested?
- Bariatric surgery
- Type of treatment
- Surgery or procedure
- How many people
- 100 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Aug 2023to 1 Mar 2026
- 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 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Participants in our patient group will be selected from the Bariatric outpatient clinic. Participants in our control group will be selected from the student campus
Who may be able to join
- Caucasian; man or women aged ≥18 years and <55 years. Females must be pre-menopausal
- Type 2 diabetes mellitus or pre-diabetes with HbA1c ≥45mmol/mol and <10% (<94mmol/mol)
- BMI ≥35
- eGFR>90 ml/min calculated as by CKD-EPI
- Provision of signed and dated, written informed consent prior to any study specific procedures
- Hypertension should be controlled, i.e., ≤ 155/95 mmHg.
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- Scheduled for gastric bypass or gastric sleeve
- Caucasian; male of female aged ≥18 years and <40 years. Females must be pre-menopausal
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Normal glucose tolerance confirmed by HbA1c
- No hypertension
- BMI ≥18,5 and <25 kg/m²
Who cannot join
- Diagnosis of type 1 diabetes mellitus
- Post-menopausal females (defined as no menses >1 year and follicle stimulating hormone (FSH) >31 U/L)
- Cardiovascular disease event in the last 6 months prior to enrollment as assessed by the investigator, including: myocardial infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina, heart failure, transient ischemic attack (TIA) or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia.
- Chronic use of sodium-glucose transporter-2 inhibitors, oral glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs), diuretics, or monoamine oxidase inhibitors.
- Current urinary tract infection or active nephritis
- History of allergy/hypersensitivity to any of the test agents
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- Contra-indication for MRI
- Any other condition that prevents participation as judged by investigator.
- Group 2: Non-diabetic lean controls
- Macro-albuminuria (defined as UACR>30 mg/mmol)
- Post-menopausal females (defined as no menses >1 year and follicle stimulating hormone (FSH) >31 U/L)*.
- Cardiovascular disease event in the last 6 months prior to enrollment as assessed by the investigator, including: myocardial infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina, heart failure, transient ischemic attack (TIA) or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia.
- Chronic use of renin-angiotensin-system blockers, sodium-glucose transporter-2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, oral glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs), diuretics ormonoamine oxidase inhibitors.
- Current urinary tract infection or active nephritis
- History of allergy/hypersensitivity to any of the test agents
- Contra-indication for MRI
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
VU University Medical Center
Amsterdam, North Holland, 1081HV
Daniel H van Raalte, MD, +31 204442974, d.vanraalte@vumc.nl
Daniel H van Raalte, MD
About this study
In this study the investigators will examine the effects of VAT reduction by bariatric surgery on kidney hypoxia and compare kidney oxygenation before- and after surgery in both sexes using BOLD-MRI and measures of kidney hemodynamic function. Furthermore, the investigators will assess whether kidney oxygenation is reduced in obese T2D men and women versus various controls as described below. This will determine whether kidney hypoxia can be appointed as a modifiable pathogenic factor in early DKD and non-surgical interventions targeting kidney hypoxia can be designed to slow DKD progression.
Read the detailed description
DKD (diabetic kidney disease) is the leading cause of chronic kidney disease (CKD) and leading to significant morbidity and early mortality. Although multiple mechanisms underlying DKD have been proposed, the exact underlying mechanisms remain uncertain resulting in limited treatment options. Accumulating evidence, derived from animal and human studies has indicated that chronic kidney hypoxia is a key underlying determinant of DKD and recent studies in T2D patients have related truncal obesity to glomerular hyperfiltration and unfavorable kidney hemodynamic function that may drive kidney hypoxia. Hyperfiltration is defined as increased whole-kidney GFR or as single-nephron hyperfiltration in people with GFR in the normal range. Hyperfiltration is an early recognized key factor driving kidney disease progression in people with diabetes as it drives subsequent eGFR loss. Increased and dysfunctional (i.e., altered adipose tissue biology) visceral adipose tissue (VAT) present in central obesity is thought to disturb the balance between kidney oxygen- consumption and delivery through secretion of endocrine signals resulting in induction of insulin resistance, mitochondrial dysfunction and impaired substrate metabolism amongst others. In line with this theory, reduction of abdominal obesity following bariatric surgery has demonstrated to improve kidney outcomes in some but not in all individuals. In part this may be sex-specific. Since women have a lower risk for progression of DKD, the role of kidney hypoxia in DKD need to be studied in this regard individualized for sex. In this study, the investigators will address the effects of bariatric surgery on changes in kidney oxygenation using a sex-specific approach in people with hyperfiltration.
- Conditions
- Kidney Hypoxia, Diabetes Mellitus, Type 2
- Being tested
- Bariatric surgery
- Keywords
- Obesity, Bariatric surgery
- Medical subject headings
- Diabetes Mellitus, Type 2, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bariatric surgeryProcedure or surgery
Patients included in our obese patient group are all scheduled to undergo bariatric surgery
| Study group | Role | What they receive |
|---|---|---|
| Obese patients | Obese patients with T2D and hyperfiltration that will undergo bariatric surgery Receives: Procedure: Bariatric surgery | |
| Healthy controls | Healthy, lean controls with BMI 20-25 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in kidney oxygenation before and after bariatric surgery
BOLD-MRI
Measured: 1 year
Secondary outcomes (2)
Difference in kidney oxygenation between men and women
BOLD-MRI
Measured: baseline, 1 year
Difference in kidney oxygenation between obese, hyperfiltering men and women with T2D versus non-diabetic lean controls
BOLD-MRI
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2024
- Study start1 Aug 2023
- Primary completion1 Jan 2026 (estimated)
- Study completion1 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney HypoxiaStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Kidney Foundation, Dutch Diabetes Research Foundation
- Responsible party
- Principal investigator, Daniel van Raalte, Amsterdam UMC, location VUmc
- Investigators
- Daniel H van Raalte, MD, Principal investigator, AmsterdamUMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06284785
- Sponsor's protocol ID
- 2023.0121
- Acronym
- ECSTASY
- Status last verified
- Feb 2024
- First submitted
- 3 Aug 2023
- Last updated
- 29 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- 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 29 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Bariatric Surgery on Kidney Oxygenation in Obese Adults With Type 2 Diabetes and Hyperfiltration
- ClinicalTrials.gov ID
- NCT06284785
- Acronym / sponsor ID
- ECSTASY / 2023.0121
- Conditions
- Kidney Hypoxia, Diabetes Mellitus, Type 2
- Keywords
- Obesity, Bariatric surgery
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- Dutch Kidney Foundation, Dutch Diabetes Research Foundation
- Study start
- 1 Aug 2023 (actual)
- Primary completion
- 1 Jan 2026 (estimated)
- Study completion
- 1 Mar 2026 (estimated)
- First posted
- 29 Feb 2024 (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.
In this study the investigators will examine the effects of VAT reduction by bariatric surgery on kidney hypoxia and compare kidney oxygenation before- and after surgery in both sexes using BOLD-MRI and measures of kidney hemodynamic function. Furthermore, the investigators will assess whether kidney oxygenation is reduced in obese T2D men and women versus various controls as described below. This will determine whether kidney hypoxia can be appointed as a modifiable pathogenic factor in early DKD and non-surgical interventions targeting kidney hypoxia can be designed to slow DKD progression.
Detailed description
DKD (diabetic kidney disease) is the leading cause of chronic kidney disease (CKD) and leading to significant morbidity and early mortality. Although multiple mechanisms underlying DKD have been proposed, the exact underlying mechanisms remain uncertain resulting in limited treatment options. Accumulating evidence, derived from animal and human studies has indicated that chronic kidney hypoxia is a key underlying determinant of DKD and recent studies in T2D patients have related truncal obesity to glomerular hyperfiltration and unfavorable kidney hemodynamic function that may drive kidney hypoxia. Hyperfiltration is defined as increased whole-kidney GFR or as single-nephron hyperfiltration in people with GFR in the normal range. Hyperfiltration is an early recognized key factor driving kidney disease progression in people with diabetes as it drives subsequent eGFR loss. Increased and dysfunctional (i.e., altered adipose tissue biology) visceral adipose tissue (VAT) present in central obesity is thought to disturb the balance between kidney oxygen- consumption and delivery through secretion of endocrine signals resulting in induction of insulin resistance, mitochondrial dysfunction and impaired substrate metabolism amongst others. In line with this theory, reduction of abdominal obesity following bariatric surgery has demonstrated to improve kidney outcomes in some but not in all individuals. In part this may be sex-specific. Since women have a lower risk for progression of DKD, the role of kidney hypoxia in DKD need to be studied in this regard individualized for sex. In this study, the investigators will address the effects of bariatric surgery on changes in kidney oxygenation using a sex-specific approach in people with hyperfiltration.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Obese patients | – | Procedure: Bariatric surgeryObese patients with T2D and hyperfiltration that will undergo bariatric surgery |
| Healthy controls | – | –Healthy, lean controls with BMI 20-25 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Participants in our patient group will be selected from the Bariatric outpatient clinic. Participants in our control group will be selected from the student campus
Key inclusion criteria (12 listed)
- Caucasian; man or women aged ≥18 years and <55 years. Females must be pre-menopausal
- Type 2 diabetes mellitus or pre-diabetes with HbA1c ≥45mmol/mol and <10% (<94mmol/mol)
- BMI ≥35
- eGFR>90 ml/min calculated as by CKD-EPI
- Provision of signed and dated, written informed consent prior to any study specific procedures
Key exclusion criteria (16 listed)
- Diagnosis of type 1 diabetes mellitus
- Post-menopausal females (defined as no menses >1 year and follicle stimulating hormone (FSH) >31 U/L)
- Cardiovascular disease event in the last 6 months prior to enrollment as assessed by the investigator, including: myocardial infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina, heart failure, transient ischemic attack (TIA) or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia.
- Chronic use of sodium-glucose transporter-2 inhibitors, oral glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs), diuretics, or monoamine oxidase inhibitors.
- Current urinary tract infection or active nephritis
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 |
|---|---|---|
| Bariatric surgeryPatients included in our obese patient group are all scheduled to undergo bariatric surgery | Procedure or surgery | Obese patients |
Primary outcome
Difference in kidney oxygenation before and after bariatric surgery
Time frame: 1 year
BOLD-MRI
2 secondary outcomes
Difference in kidney oxygenation between men and women
Time frame: baseline, 1 year
Difference in kidney oxygenation between obese, hyperfiltering men and women with T2D versus non-diabetic lean controls
Time frame: Baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Feb 2024.
- 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.
Daniel H van Raalte, MD principal investigator
AmsterdamUMC
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 Kidney Hypoxia and Diabetes Mellitus, Type 2, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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 12 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 29 Feb 2024. 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 Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact D.H. van Raalte, MD (+31 204442974, d.vanraalte@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in kidney oxygenation before and after bariatric surgery (time frame: 1 year). 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 29 Feb 2024.