Impact of Metabolic Surgery on Pancreatic, Renal and Cardiovascular Health in Youth With Type 2 Diabetes (IMPROVE-T2D)
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|ClinicalTrials.gov Identifier: NCT03620773|
Recruitment Status : Recruiting
First Posted : August 8, 2018
Last Update Posted : August 2, 2019
Type 2 diabetes (T2D) in youth is increasing in prevalence in parallel with the obesity epidemic. In the US, almost half of patients with renal failure have DKD, and ≥80% have T2D. Compared to adult-onset T2D, youth with T2D have a more aggressive phenotype with greater insulin resistance (IR), more rapid β-cell decline and higher prevalence of diabetic kidney disease (DKD), arguing for separate and dedicated studies in youth-onset T2D. Early DKD is characterized by changes in intrarenal hemodynamic function, including increased renal plasma flow (RPF) and glomerular pressure with resultant hyperfiltration, is common in Y-T2D, and predicts progressive DKD.
Studies evaluating the two currently approved medications for treating T2D in youth (metformin and insulin) have shown these medications are not able to improve β-cell function over time in the youth. However, recent evidence suggests that bariatric surgery in adults is associated with improvements in diabetes outcomes, and even T2D remission in many patients. Limited data in youth also supports the benefits of bariatric surgery, regarding weight loss, glycemic control in T2D, and cardio-renal health. While weight loss is important, the acute effect of bariatric surgery on factors such as insulin resistance likely includes weight loss-independent mechanisms. A better understanding of the effects of bariatric surgery on pancreatic function, intrarenal hemodynamics, renal O2 and cardiovascular function is critical to help define mechanisms of surgical benefits, to help identify potential novel future non-surgical approaches to prevent pancreatic failure, DKD and cardiovascular disease.
The investigators' overarching hypotheses are that: 1) Y-T2D is associated with IR, pancreatic dysfunction, intrarenal hemodynamic dysfunction, elevated renal O2 consumption and cardiovascular dysfunction which improve with bariatric surgery, 2) The early effect of bariatric surgery on intrarenal hemodynamics is mediated by improvement in IR and weight loss. To address these hypotheses, the investigators will measure GFR, RPF, glomerular pressure and renal O2, in addition to aortic stiffness, β-cell function and insulin sensitivity in youth ages 12-21 with T2D (n=30) before and after vertical sleeve gastrectomy (VSG).
|Condition or disease||Intervention/treatment||Phase|
|Type 2 Diabetes Mellitus Obesity Bariatric Surgery Candidate Nephropathy Diabetic Kidney Disease Diabetes Mellitus, Type 2 Diabetes Mellitus Diabetes Complications Weight Loss Diabetic Nephropathies Adolescent Obesity Pediatric Obesity||Drug: Aminohippurate Sodium Inj 20% Drug: Iohexol Inj 300 mg/mL Procedure: Vertical Sleeve Gastrectomy||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||All participants in this study will receive the same intervention.|
|Masking:||None (Open Label)|
|Official Title:||IMPROVE-T2D Study: Impact of Metabolic Surgery on Pancreatic, Renal and Cardiovascular Health in Youth With Type 2 Diabetes|
|Actual Study Start Date :||October 1, 2018|
|Estimated Primary Completion Date :||August 2023|
|Estimated Study Completion Date :||August 2023|
Participants will include youth who are scheduled for, and will undergo, vertical sleeve gastrectomy (VSG) surgery at the Bariatric Surgery Clinic at Children's Hospital of Colorado.
To understand how bariatric surgery affects renal function, all participants will undergo assessment of Glomerular Filtration Rate, (Iohexol Inj 300 mg/mL) and Effective Renal Plasma Flow (Aminohippurate Sodium Inj 20%). In addition, participants will undergo imaging assessment that includes renal Blood Oxygen Level Dependent (BOLD) and Arterial Spin Labeling (ASL) MRI.
Drug: Aminohippurate Sodium Inj 20%
Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)
Drug: Iohexol Inj 300 mg/mL
Diagnostic aid/agent used to measure glomerular filtration rate (GFR)
Other Name: omnipaque 300
Procedure: Vertical Sleeve Gastrectomy
Participants will undergo vertical sleeve gastrectomy surgery, a laparoscopic bariatric surgery procedure designed for weight loss in obese patients
Other Name: Bariatric Surgery
- Pancreatic β-cell function [ Time Frame: 4 hours (MMTT) ]Measured by Mixed Meal Tolerance Test (MMTT)
- Pancreatic β-cell function [ Time Frame: 4 hours (hyperglycemic clamp) ]Measured by blood draws during/after hyperglycemic clamp
- Effective Renal Plasma Flow (ERPF) [ Time Frame: 4 hours ]Measured by PAH clearance
- Glomerular Filtration Rate (GFR) [ Time Frame: 4 hours ]Measured by iohexol clearance
- Renal Perfusion [ Time Frame: 10 min ]Measured by Arterial Spin Labeling (ASL) MRI
- Renal Oxygenation [ Time Frame: 60 min ]Measured by Blood Oxygen Level Dependent (BOLD) MRI
- Aortic Stiffness & Wall Shear Stress [ Time Frame: 30 min ]Measured by Aortic MRI
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03620773
|Contact: Susan Gross, MS, RDfirstname.lastname@example.org|
|Contact: Petter Bjornstad, MDemail@example.com|
|United States, Colorado|
|Children's Hospital Colorado||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Petter Bjornstad, MD 720-777-4659 firstname.lastname@example.org|
|Principal Investigator: Petter Bjornstad, M.D.|
|Sub-Investigator: Kristin Nadeau, M.D.|
|Principal Investigator:||Petter Bjornstad, MD||University of Colorado School of Medicine|