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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05008276
• Other study ID #: 21-3019
• Status: Recruiting
• Start date: September 27, 2021
• Est. completion date: December 1, 2027

Study information

• Verified date: April 2024
• Source: University of Colorado, Denver
• Contact: Petter Bjornstad, MD
• Phone: 720-777-4659
• Email: Petter.M.Bjornstad[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

Puberty is a complex process of physiological changes, including neuroreproductive and growth hormone activation and rapid organ growth, that may predispose organs to injury. The kidneys may be especially susceptible because they are highly metabolically active and second only to the heart with respect to oxygen consumption per tissue mass. During puberty, the kidneys almost double in size, likely increasing the kidneys' already high energy expenditure. In parallel, puberty is associated with physiologic insulin resistance (IR), which is accentuated in obesity. Our central hypothesis is that obese youth with prediabetes and T2D experience relative kidney hypoxia during puberty due to a metabolic mismatch between increased energy expenditure and impaired substrate metabolism. In turn, the kidney hypoxia results in loss of glomerular charge and size selectivity leading to increased transglomerular transport of protein and kidney dysfunction. Our preliminary data showed that pubertal adolescents with obesity and/or diabetes exhibit relative kidney hypoxia compared to normal weight controls using functional magnetic resonance imaging (MRI) and that relative kidney hypoxia is greater in late vs. early puberty. However, determining the pubertal mechanisms contributing to kidney injury in youth with obesity and T2D requires serial evaluations throughout puberty. To assess the impact of pubertal changes within a 5-year study period, the investigators propose an accelerated longitudinal study design in which the investigators will enroll adolescents (8-14 years, 50% girls) with obesity and/or elevated hemoglobin A1c (HbA1c ≥6%) [n=60], and healthy normoglycemic controls [n=40] at Tanner (pubertal) stages 1-4 and examine them at baseline, 1 and 2-years. The investigators will then compare data by Tanner stage to construct an integrated portrayal of the physiological changes that occur throughout puberty. Given the rarity of T2D prior to pubertal onset, the investigators chose to enroll a high high-risk group: youth with obesity and/or HbA1c ≥6.0% to represent youth ranging from those at magnified risk of developing T2D to those recently diagnosed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 1, 2027
• Est. primary completion date: December 1, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 14 Years

Eligibility

Inclusion Criteria:

• HbA1c =6.0% for untreated high-risk group

• BMI = 95th %ile for high-risk group

• Normal HbA1c =5.6% for control group

• Type 1 diabetes (T1D) Antibody negative

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Adolescent Obesity
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetic Kidney Disease
• Diabetic Nephropathies
• Hypoxia
• Kidney Diseases
• Pediatric Obesity
• Pre Diabetes
• Prediabetic State
• Puberty
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Aminohippurate Sodium Inj 20%
Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)
• Iohexol Inj 300 MG/ML
Diagnostic aid/agent used to measure glomerular filtration rate (GFR)
• Dextran 40
Diagnostic aid/agent used to measure glomerular size and selectivity

Locations

Country	Name	City	State
United States	Children's Hospital Colorado	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effective renal plasma flow (ERPF)	Measured by PAH Clearance	3 Hours
Primary	Glomerular Filtration Rate (GFR)	Measured by iohexol clearance	3 hours
Secondary	Insulin Sensitivity	Measured by IV glucose tolerance test (IVGTT)	3 hours
Secondary	Renal perfusion	Arterial spin labeling (ASL) MRI	10 min
Secondary	Renal oxygenation	Blood oxygen level dependent (BOLD) MRI	60 min