Type 2 Diabetes MellitusNCT05008276
Puberty, Diabetes, and the Kidneys, When Eustress Becomes Distress (PANTHER Study)
An observational study of Type 2 Diabetes Mellitus and Diabetic Kidney Disease, run by Petter Bjornstad at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 8 to 14 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus, Diabetic Kidney Disease, Adolescent Obesity
- What is being tested?
- Aminohippurate Sodium Inj 20%, Iohexol Inj 300 MG/ML and Dextran 40
- How many people
- 100 participants
- Where
- 2 sitesUnited States
- Study dates
- 27 Sep 2021to 1 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 8 to 14 years
- All sexes
- Healthy volunteers accepted
- Child
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Megan Kelsey, MD, MS, 720-777-0991, Megan.Kelsey@childrenscolorado.org
Megan Kelsey, MD, MS
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98102
Petter M Bjornstad, MD, (206) 616 3543, pettermb@uw.edu
Petter M Bjornstad, MD
About this study
Official title: PANTHER Study: Puberty, Diabetes, and the Kidneys, When Eustress Becomes Distress
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.
Read the detailed 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.
- Conditions
- Type 2 Diabetes Mellitus, Diabetic Kidney Disease, Adolescent Obesity, Pre Diabetes, Kidney Hypoxia, Puberty
- Being tested
- Aminohippurate Sodium Inj 20%, Iohexol Inj 300 MG/ML, Dextran 40
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetic Nephropathies, Pediatric Obesity, Glucose Intolerance
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 Sodium 4-amino hippurate (PAH) inj 20% 2g/10mL, Para-aminohippurate, Aminohippuric acid
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)
Dextran 40Drug
Also called Dextran Sieving
Diagnostic aid/agent used to measure glomerular size and selectivity
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Aminohippurate Sodium Inj 20%; Drug: Iohexol Inj 300 MG/ML; Drug: Dextran 40 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effective renal plasma flow (ERPF)
Measured by PAH Clearance
Measured: 3 Hours
Glomerular Filtration Rate (GFR)
Measured by iohexol clearance
Measured: 3 hours
Secondary outcomes (3)
Insulin Sensitivity
Measured by IV glucose tolerance test (IVGTT)
Measured: 3 hours
Renal perfusion
Arterial spin labeling (ASL) MRI
Measured: 10 min
Renal oxygenation
Blood oxygen level dependent (BOLD) MRI
Measured: 60 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2021
- Study start27 Sep 2021
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Petter Bjornstad
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Seattle Children's Hospital, University of Colorado, Denver
- Responsible party
- Sponsor-investigator, Petter Bjornstad, Seattle Children's Hospital
- Investigators
- Petter Bjornstad, MD, Principal investigator, University of Washington - Medicine Diabetes Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05008276
- Sponsor's protocol ID
- 21-3019
- Status last verified
- Mar 2025
- First submitted
- 9 Aug 2021
- Last updated
- 24 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PANTHER Study: Puberty, Diabetes, and the Kidneys, When Eustress Becomes Distress
- ClinicalTrials.gov ID
- NCT05008276
- Acronym / sponsor ID
- 21-3019
- Conditions
- Type 2 Diabetes Mellitus, Diabetic Kidney Disease, Adolescent Obesity, Pre Diabetes, Kidney Hypoxia, Puberty
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Petter BjornstadUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Seattle Children's Hospital, University of Colorado, Denver
- Study start
- 27 Sep 2021 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 17 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Youth with overweight/obesity and/or newly diagnosed T2D and elevated HbA1c | – | Drug: Aminohippurate Sodium Inj 20%, Drug: Iohexol Inj 300 MG/ML, Drug: Dextran 40All 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 |
| Healthy normal-weight controls | – | Drug: Aminohippurate Sodium Inj 20%, Drug: Iohexol Inj 300 MG/ML, Drug: Dextran 40All 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 |
Who may qualify
- Ages
- 8 to 14 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- 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.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- History of Chronic kidney disease (CKD) or acute kidney injury (AKI)
- Metabolic disorder prohibiting safe fasting
- Iodine or penicillin allergy
- Pregnancy
- Thrombophilia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aminohippurate Sodium Inj 20%Also: Sodium 4-amino hippurate (PAH) inj 20% 2g/10mL, Para-aminohippurate, Aminohippuric acidDiagnostic aid/agent used to measure effective renal plasma flow (ERPF) | Drug | Healthy normal-weight controls, Youth with overweight/obesity and/or newly diagnosed T2D and elevated HbA1c |
| Iohexol Inj 300 MG/MLAlso: omnipaque 300Diagnostic aid/agent used to measure glomerular filtration rate (GFR) | Drug | Healthy normal-weight controls, Youth with overweight/obesity and/or newly diagnosed T2D and elevated HbA1c |
| Dextran 40Also: Dextran SievingDiagnostic aid/agent used to measure glomerular size and selectivity | Drug | Healthy normal-weight controls, Youth with overweight/obesity and/or newly diagnosed T2D and elevated HbA1c |
Primary outcome
Effective renal plasma flow (ERPF)
Time frame: 3 Hours
Measured by PAH Clearance
Glomerular Filtration Rate (GFR)
Time frame: 3 hours
Measured by iohexol clearance
3 secondary outcomes
Insulin Sensitivity
Time frame: 3 hours
Renal perfusion
Time frame: 10 min
Renal oxygenation
Time frame: 60 min
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Petter Bjornstad, MD principal investigator
University of Washington - Medicine Diabetes Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 2 Diabetes Mellitus and Diabetic Kidney Disease, run by Petter Bjornstad at 2 sites 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 4 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Petter Bjornstad, MD ((206) 616 3543, pettermb@uw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effective renal plasma flow (ERPF) (time frame: 3 Hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Mar 2025; AzTrials last refreshed its copy on 7 Nov 2026.