The Effects of Bariatric Surgery on Kidney Oxygenation in Obese Adults With Type 2 Diabetes and Hyperfiltration (ECSTASY)

February 28, 2024 updated by: Daniel van Raalte, Amsterdam UMC, location VUmc
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Netherlands
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1081HV
        • Recruiting
        • VU University Medical Center
        • Contact:
        • Principal Investigator:
          • Daniel H van Raalte, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

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

Description

Group 1: T2DM patients with obesity and hyperfiltration

Inclusion criteria:

  • 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.
  • Scheduled for gastric bypass or gastric sleeve

Exclusion criteria:

  • 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
  • Contra-indication for MRI
  • Any other condition that prevents participation as judged by investigator.

Group 2: Non-diabetic lean controls

Inclusion criteria:

  • 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

Exclusion criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Obese patients
Obese patients with T2D and hyperfiltration that will undergo bariatric surgery
Procedure: Bariatric surgery
Patients included in our obese patient group are all scheduled to undergo bariatric surgery
Healthy controls
Healthy, lean controls with BMI 20-25

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in kidney oxygenation before and after bariatric surgery
Time Frame: 1 year
BOLD-MRI
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in kidney oxygenation between men and women
Time Frame: baseline, 1 year
BOLD-MRI
baseline, 1 year
Difference in kidney oxygenation between obese, hyperfiltering men and women with T2D versus non-diabetic lean controls
Time Frame: Baseline
BOLD-MRI
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amsterdam UMC, location VUmc

Collaborators

Dutch Kidney Foundation
Dutch Diabetes Research Foundation

Investigators

  • Principal Investigator: Daniel H van Raalte, MD, AmsterdamUMC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2023

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

March 1, 2026

Study Registration Dates

First Submitted

August 3, 2023

First Submitted That Met QC Criteria

February 28, 2024

First Posted (Actual)

February 29, 2024

Study Record Updates

Last Update Posted (Actual)

February 29, 2024

Last Update Submitted That Met QC Criteria

February 28, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023.0121

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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