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Type 2 Diabetes MellitusPhase 1/2IMPROVE-T2DNCT03620773

Impact of Metabolic Surgery on Pancreatic, Renal and Cardiovascular Health in Youth With Type 2 Diabetes

A Phase 1/2 study testing Aminohippurate Sodium Inj 20%, Iohexol Inj 300 mg/mL and Vertical Sleeve Gastrectomy in people with Type 2 Diabetes Mellitus and Obesity, run by University of Colorado, Denver at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 to 21 years
What is being tested?
Aminohippurate Sodium Inj 20%, Iohexol Inj 300 mg/mL and Vertical Sleeve Gastrectomy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
1 Oct 2018to 25 Sep 2024
Phase
Phase 1/2
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 12 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Obese youth with and without T2D (≥50 kg) scheduled for VSG
  • Weight <550 lbs.
  • BMI ≥ 35 kg/m2
  • Age 12-21 years
  • HbA1c ≤ 12% for participants with T2D, HbA1c < 6.5% for participants with obesity

Who cannot join

  • Obesity or T2D onset (diagnosis) > 18 years of age
  • Prepubertal
  • Anemia
  • For participants undergoing the optional Parts 2-4 of visits 2 and 4, seafood or iodine allergy
  • Pregnancy or breastfeeding
  • Claustrophobia, implantable devices (MRI contraindications)
Show all 26Show fewer
  • Recent diabetic ketoacidosis or hyperosmolar hyperglycemia
  • Other causes of diabetes other than T2D
  • For participants undergoing the optional Parts 2-4 of visits 2 and 4, 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
  • Additional exclusion criteria for participants undergoing Visit 4 part 4, the optional kidney biopsy:
  • Evidence of bleeding disorder or complications from bleeding
  • Use of aspirin, NSAIDS or other blood thinner that cannot be safely stopped for a sufficient time period before and after the biopsy so as to add no additional risk of bleeding
  • Blood urea nitrogen (BUN) > 80 gm/dL
  • INR > 1.4
  • PTT > 35 seconds
  • Hemoglobin (Hgb) < 10 mg/dL
  • Platelet count < 100,000 / µL
  • Uncontrolled or difficult to control hypertension (> 150/90 mmHg at the day of biopsy)
  • eGFR < 40 mL/min/1.73m2
  • Single kidney (either by history, documented by prior imaging or ultrasound performed prior to the biopsy)
  • > 2 cm discrepancy between left and right kidney sizes based on largest longitudinal diameter determined by ultrasound performed prior to the biopsy.
  • Kidney size: One or both kidneys < 9 cm
  • Hydronephrosis or other important renal ultrasound findings such as significant stone disease
  • Any evidence of a current urinary tract infection as indicated on day of biopsy
  • Clinical evidence of non-diabetic renal disease
  • Positive urine pregnancy test or pregnancy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

Other trials in United States

About this study

Official title: IMPROVE-T2D Study: Impact of Metabolic Surgery on Pancreatic, Renal and Cardiovascular Health in Youth With Type 2 Diabetes

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 in youth with obesity with or without diabetes 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, 3) Some aspects of cardio-renal-metabolic complications of T2D are related to obesity and others to T2D independent of obesity. 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=40) and in (n=up to 10) youth with similar BMI but without diabetes, before and after vertical sleeve gastrectomy (VSG). To further investigate the mechanisms of renal damage in youth with T2D, two optional procedures are included in the study prior to vertical sleeve gastrectomy: 1) kidney biopsy procedure and 2) induction of induced pluripotent stem cells (iPSCs) to assess morphometrics and genetic expression of renal tissue.

Being tested
Aminohippurate Sodium Inj 20%, Iohexol Inj 300 mg/mL, Vertical Sleeve Gastrectomy, Renal Biopsy
Medical subject headings
Diabetes Mellitus, Type 2, Obesity, Kidney Diseases, Diabetic Nephropathies, Diabetes Mellitus, Diabetes Complications, Weight Loss, Pediatric Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aminohippurate Sodium Inj 20%Drug

    Also called Aminohippuric acid, Para-aminohippurate, Sodium 4-amino hippurate (PAH) inj 20% 2g/10 mL

    Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)

  • Iohexol Inj 300 mg/mLDrug

    Also called omnipaque 300

    Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

  • Vertical Sleeve GastrectomyProcedure or surgery

    Also called Bariatric Surgery

    Participants will undergo vertical sleeve gastrectomy surgery, a laparoscopic bariatric surgery procedure designed for weight loss in obese patients

  • Renal BiopsyProcedure or surgery

    Also called Kidney Biopsy

    Minimally invasive outpatient procedure in interventional radiology to obtain renal tissue cores.

Study groups in NCT03620773
Study groupRoleWhat they receive
Clinical InvestigationOtherParticipants 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.
Receives: Drug: Aminohippurate Sodium Inj 20%; Drug: Iohexol Inj 300 mg/mL; Procedure: Vertical Sleeve Gastrectomy; Procedure: Renal Biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pancreatic β-cell function

    Measured by Mixed Meal Tolerance Test (MMTT)

    Measured: 4 hours (MMTT)

  2. Pancreatic β-cell function

    Measured by blood draws during/after hyperglycemic clamp

    Measured: 4 hours (hyperglycemic clamp)

  3. Effective Renal Plasma Flow (ERPF)

    Measured by PAH clearance

    Measured: 4 hours

  4. Glomerular Filtration Rate (GFR)

    Measured by iohexol clearance

    Measured: 4 hours

Secondary outcomes (3)

  1. Renal Perfusion

    Measured by Arterial Spin Labeling (ASL) MRI

    Measured: 10 min

  2. Renal Oxygenation

    Measured by Blood Oxygen Level Dependent (BOLD) MRI

    Measured: 60 min

  3. Aortic Stiffness & Wall Shear Stress

    Measured by Aortic MRI

    Measured: 30 min

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Aug 2018
  2. Study start1 Oct 2018
  3. Primary completion25 Sep 2024
  4. Study completion25 Sep 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Model description
All participants in this study will receive the same intervention.
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03620773
Sponsor's protocol ID
18-0704
Acronym
IMPROVE-T2D
Status last verified
Jan 2026
First submitted
1 Aug 2018
Last updated
12 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Dobbs TJ, Pyle L, Moore JM, Garrish J, Behn CD, Weissenkampen D, Baumgartner AD, Gross S, Schutte G, Birznieks C, Melena I, Remmers L, Driscoll L, Cree MG, Kelsey MM, Shah AS, Inge TH, Bjornstad P, Nadeau KJ. Impact of Vertical Sleeve Gastrectomy in Youth-Onset Type 2 Diabetes: Changes in Glycemia, Insulin Sensitivity, and Secretion. Obesity (Silver Spring). 2026 Jun;34 Suppl 1:121-133. doi: 10.1002/oby.70140. Epub 2026 Feb 18.

    PubMed 41708511

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Aminohippurate Sodium Inj 20%, Iohexol Inj 300 mg/mL and Vertical Sleeve Gastrectomy in people with Type 2 Diabetes Mellitus and Obesity, run by University of Colorado, Denver at 1 site in United States.

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 5 inclusion and 26 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 12 Jan 2026. 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 United States. 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.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Pancreatic β-cell function (time frame: 4 hours (MMTT)). 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?

On the ClinicalTrials.gov record for NCT03620773, which also lists 1 linked publication.

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 12 Jan 2026.

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