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Impact of Metabolic Surgery on Pancreatic, Renal and Cardiovascular Health in Youth With Type 2 Diabetes (IMPROVE-T2D)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03620773
Recruitment Status : Recruiting
First Posted : August 8, 2018
Last Update Posted : August 2, 2019
Information provided by (Responsible Party):
Petter Bjornstad, University of Colorado, Denver

Brief Summary:

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

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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)
Primary Purpose: Diagnostic
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

Resource links provided by the National Library of Medicine

Drug Information available for: Iohexol

Arm Intervention/treatment
Clinical Investigation

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)
Other Names:
  • Aminohippuric acid
  • Para-aminohippurate
  • Sodium 4-amino hippurate (PAH) inj 20% 2g/10 mL

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

Primary Outcome Measures :
  1. Pancreatic β-cell function [ Time Frame: 4 hours (MMTT) ]
    Measured by Mixed Meal Tolerance Test (MMTT)

  2. Pancreatic β-cell function [ Time Frame: 4 hours (hyperglycemic clamp) ]
    Measured by blood draws during/after hyperglycemic clamp

  3. Effective Renal Plasma Flow (ERPF) [ Time Frame: 4 hours ]
    Measured by PAH clearance

  4. Glomerular Filtration Rate (GFR) [ Time Frame: 4 hours ]
    Measured by iohexol clearance

Secondary Outcome Measures :
  1. Renal Perfusion [ Time Frame: 10 min ]
    Measured by Arterial Spin Labeling (ASL) MRI

  2. Renal Oxygenation [ Time Frame: 60 min ]
    Measured by Blood Oxygen Level Dependent (BOLD) MRI

  3. Aortic Stiffness & Wall Shear Stress [ Time Frame: 30 min ]
    Measured by Aortic MRI

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   12 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Obese youth with T2D (≥50 kg) scheduled for VSG
  • Weight <550 lbs.
  • BMI ≥ 35 kg/m2
  • Age 12-21 years
  • HbA1c ≤ 12%

Exclusion Criteria:

  • T2D onset (diagnosis) > 18 years of age
  • Prepubertal
  • Anemia
  • Seafood or iodine allergy
  • Pregnancy or breastfeeding
  • Claustrophobia, implantable devices (MRI contraindications)
  • Recent diabetic ketoacidosis or hyperosmolar hyperglycemia
  • Other causes of diabetes other than T2D
  • Diuretics, sodium-glucose co-transport (SGLT) 2 or 1 blockers, daily NSAIDs or aspirin, sulfonamides, procaine, thiazolsulfone or probenecid, atypical antipsychotics or regular use of oral steroids

Information from the National Library of Medicine

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 identifier (NCT number): NCT03620773

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Contact: Susan Gross, MS, RD 720-777-6143
Contact: Petter Bjornstad, MD 720-777-4659

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United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Petter Bjornstad, MD    720-777-4659   
Principal Investigator: Petter Bjornstad, M.D.         
Sub-Investigator: Kristin Nadeau, M.D.         
Sponsors and Collaborators
University of Colorado Denver School of Medicine Barbara Davis Center
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Principal Investigator: Petter Bjornstad, MD University of Colorado School of Medicine

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Responsible Party: Petter Bjornstad, Assistant Professor, University of Colorado, Denver Identifier: NCT03620773    
Other Study ID Numbers: 18-0704
First Posted: August 8, 2018    Key Record Dates
Last Update Posted: August 2, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Diseases
Diabetic Nephropathies
Diabetes Mellitus
Diabetes Mellitus, Type 2
Pediatric Obesity
Diabetes Complications
Weight Loss
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Nutrition Disorders
Body Weight
Signs and Symptoms
Urologic Diseases
Body Weight Changes