Puberty, Diabetes, and the Kidneys, When Eustress Becomes Distress (PANTHER Study)

NCT05008276 | Recruiting FDA Drug

• 1 other identifier: 21-3019
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

Early diabetic kidney disease (DKD) occurs in 50-70% of youth with type 2 diabetes (T2D) and confers high lifetime risk of dialysis and premature death. Youth-onset T2D typically manifests during or shortly after puberty in adolescents with obesity. Epidemiological data implicate puberty as an accelerator of kidney disease in youth with obesity and diabetes and the investigators posit that the link between puberty and T2D-onset may explain the high burden of DKD in youth-onset T2D. A better understanding of the impact of puberty on kidney health is needed to promote preservation of native kidney function, especially in youth with T2D.

Conditions

Type 2 Diabetes Mellitus; Diabetic Kidney Disease; Adolescent Obesity; Pre Diabetes; Kidney Hypoxia; Puberty

Outcome Measures

Primary Outcomes (2)

• Effective renal plasma flow (ERPF)

  Measured by PAH Clearance

  3 Hours

• Glomerular Filtration Rate (GFR)

  Measured by iohexol clearance

  3 hours

Secondary Outcomes (3)

• Insulin Sensitivity

  3 hours

• Renal perfusion

  10 min

• Renal oxygenation

  60 min

Study Arms (2)

Youth with overweight/obesity and/or newly diagnosed T2D and elevated HbA1c

All participants will undergo GFR (Iohexol Inj 300 MG/ML), EPRF (Aminohippurate Sodium Inj 20%), Dextran sieving (Dextran 40 Sodium Inj 0.9%), IVGTT for insulin sensitivity, in addition to BOLD and ASL Kidney MRI

Drug: Aminohippurate Sodium Inj 20%; Drug: Iohexol Inj 300 MG/ML; Drug: Dextran 40

Healthy normal-weight controls

All participants will undergo GFR (Iohexol Inj 300 MG/ML), EPRF (Aminohippurate Sodium Inj 20%), Dextran sieving (Dextran 40 Sodium Inj 0.9%), IVGTT for insulin sensitivity, in addition to BOLD and ASL Kidney MRI

Drug: Aminohippurate Sodium Inj 20%; Drug: Iohexol Inj 300 MG/ML; Drug: Dextran 40

Interventions

Aminohippurate Sodium Inj 20% DRUG

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

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

Healthy normal-weight controls; Youth with overweight/obesity and/or newly diagnosed T2D and elevated HbA1c

Iohexol Inj 300 MG/ML DRUG

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

Also known as: omnipaque 300

Healthy normal-weight controls; Youth with overweight/obesity and/or newly diagnosed T2D and elevated HbA1c

Dextran 40 DRUG

Diagnostic aid/agent used to measure glomerular size and selectivity

Also known as: Dextran Sieving

Healthy normal-weight controls; Youth with overweight/obesity and/or newly diagnosed T2D and elevated HbA1c

Eligibility Criteria

• Age: 8 Years - 14 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

The investigators propose to address the specific aims of this study in an accelerated longitudinal project with 40 adolescents with normal HbA1c (≤5.6%) and 60 with overweight/obesity and/or newly diagnosed T2D (BMI≥85%ile) and elevated HbA1c (≥6.0%) or on anti-diabetic medications ranging from TS 1-4 (Ages 8-14 yr). They will be studied annually for 2 years.

You may qualify if:

• HbA1c ≥6.0% for untreated high-risk group
• BMI ≥ 85th %ile for high-risk group
• Normal HbA1c ≤5.6% for control group
• Type 1 diabetes (T1D) Antibody negative

You may not qualify if:

• History of Chronic kidney disease (CKD) or acute kidney injury (AKI)
• Metabolic disorder prohibiting safe fasting
• Iodine or penicillin allergy
• Pregnancy
• Thrombophilia
• MRI contraindications
• Hormone therapy

Sponsors & Collaborators

• Petter Bjornstad: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Seattle Children's Hospital: collaborator
• University of Colorado, Denver: collaborator

Study Sites (2)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98102, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

During the study, the investigators will collect blood and urine samples for assessment of kidney function and kidney injury markers.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetic Nephropathies; Pediatric Obesity; Glucose Intolerance

Interventions

p-Aminohippuric Acid; Iohexol; Dextrans

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperglycemia

Intervention Hierarchy (Ancestors)

Aminohippuric Acids; Hippurates; Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Keto Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triiodobenzoic Acids; Iodobenzoates; Glucans; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates

Study Officials

• Petter Bjornstad, MD

  University of Washington - Medicine Diabetes Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Petter Bjornstad, MD

CONTACT

(206) 616 3543; pettermb@uw.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 9, 2021
• First Posted: August 17, 2021
• Study Start: September 27, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 24, 2025

Record last verified: 2025-03

Locations

US (2)