Type 1 DiabetesPANDANCT05319990
Pathogenesis of Kidney Disease in Type 1 Diabetes: a Modern Kidney Biopsy Cohort (The PANDA Study)
An observational study of Type 1 Diabetes and Diabetic Kidney Disease, run by University of Colorado, Denver at 1 site in United States.
Trial summary
Diabetic kidney disease (DKD) occurs in up to 40% of people with type 1 diabetes (T1D), often leading to kidney failure and markedly magnifying risks of cardiovascular disease and premature death. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 1 Diabetes, Diabetic Kidney Disease, Diabetes Complications
- What is being tested?
- Aminohippurate Sodium Inj 20% Diagnostic aid/agent used to measure effective renal plasma flow (ERPF) and Iohexol Inj 300 MG/ML Diagnostic aid/agent used to measure glomerular filtration rate (GFR)
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Mar 2022to 31 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The investigators propose to address the specific aims of this study in a cross-sectional project with 70 newly enrolled adults with T1D and 30 former CROCODILE participants (COMIRB #19-1282).
Who may be able to join
- Age ≥ 18 years at enrollment (rationale: this study focuses on determinants of early DKD over the course of T1D in adults)
- T1D duration >5 years (rationale: DKD in T1D rarely manifests prior to 5 years of disease duration)
- HbA1c <11% (rationale: HbA1c ≥ 11% exceeds the average HbA1c at most academic center and would limiting the generalizability of our study findings)
Who cannot join
- T2D and monogenic diabetes (rationale: our study focuses on T1D)
- Recent diabetic ketoacidosis, i.e., <1 month (rationale: safety and insulin resistance and tubular dysfunction of DKA can confound study findings)
- eGFR < 30 ml/min/1.73m2 or dialysis treatment (rationale: to reduce the likelihood of identifying secondary pathways that are not specific to kidney injury from T1D)
- Kidney transplant recipients (rationale: molecular confounding from immunosuppression)
- Kidney biopsy contraindications (rationale: safety - kidney biopsy):
- Evidence of bleeding disorder or complications from bleeding
Show all 18Show fewer
- Use of aspirin, Nonsteroidal anti-inflammatory drugs (NSAIDS) or other blood thinner that cannot be safely stopped for a sufficient time before and after the biopsy to avoid additional risk of bleeding.
- INR > 1.4
- Hemoglobin (Hgb) < 10 mg/dL (Colorado) [altitude]
- Hemoglobin (Hgb) < 9 mg/dL (Washington)
- Platelet count < 100,000 / µL
- Uncontrolled or difficult to control hypertension (> 150/90 mmHg at the day of biopsy)
- Single kidney (either by history, documented by prior imaging or ultrasound performed prior to the biopsy)
- Kidney size: One or both kidneys < 8 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
About this study
Diabetic kidney disease (DKD) occurs in up to 40% of people with type 1 diabetes (T1D), often leading to kidney failure and markedly magnifying risks of cardiovascular disease and premature death. Landmark T1D kidney biopsy studies identified the classic pathological lesions of DKD, which have been attributed largely to hyperglycemia. Recent advances in continuous glucose monitoring (CGM) and automated insulin delivery have facilitated improved glycemic control, but the residual risk of DKD continues to be high. In addition, obesity and insulin resistance (IR) have accompanied intensive glycemic therapy and may promote mitochondrial dysfunction and inflammation. Deciphering the molecular underpinnings of DKD in modern-day T1D and identifying modifiable risk factors could lead to more effective and targeted therapies to prevent DKD.
Read the detailed description
The overall goal of this project is to characterize the molecular, morphometric, and metabolic features of DKD over the modern clinical course of T1D. The investigators hypothesize that perturbed kidney energetics and hypoxia are central metabolic pathways in the development of DKD. Kidney hypoxia stems from a mismatch between increased renal energy demand (e.g., increased glomerular filtration rate [GFR] and tubular reabsorption of sodium) and impaired substrate metabolism (e.g., IR and mitochondrial dysfunction) and results in activation of the hypoxia-inducible factor (HIF) system. Although upregulation of HIF1α confers favorable short-term effects, sustained activation promotes cellular injury. Supporting these hypotheses, data from our group and others have shown that obesity, IR, and The investigators also found that youth with T1D exhibit kidney hypoxia by MRI that strongly associates with IR and mitochondrial dysfunction. Moreover, our preliminary single-cell RNA sequencing (scRNA-seq) data from kidney biopsies demonstrate upregulated tubular expression of HIF1α in adults with T1D vs. healthy controls. The investigators propose to build a unique new longitudinal kidney biopsy cohort (N=100) spanning the critical duration of T1D over which DKD initiates and progresses (5-30 years). Participants will be enrolled from our existing CROCODILE study (adding longitudinal follow-up to completed kidney biopsies and baseline data and biosample acquisition) and from new enrollment at the University of Colorado and University of Washington. Normative kidney biopsy data will be provided from our existing cohort of healthy controls (N=20) and the Kidney Precision Medicine Project (KPMP). The investigators will implement state-of-the-art molecular (scRNA-seq) and morphometric interrogation of kidney tissue and rigorous metabolic phenotyping to include kidney magnetic resonance imaging (MRI), direct measurements of glycemia (continuous glucose monitoring), intraabdominal fat (dual-energy X-ray absorptiometry), estimation of insulin sensitivity by a T1D-validated equation, and (in a subset) GFR (iohexol clearance) and renal plasma flow (p-aminohippurate clearance). Participants will be followed longitudinally for DKD outcomes. A subset of 20 participants will undergo repeat kidney biopsies and associated procedures 3 years after baseline kidney biopsy.
- Conditions
- Type 1 Diabetes, Diabetic Kidney Disease, Diabetes Complications, Diabetic Nephropathies, Autoimmune Diabetes
- Being tested
- 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)
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetic Nephropathies, Diabetes Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aminohippurate Sodium Inj 20% Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)Drug
Also called Sodium 4-amino hippurate (PAH) inj 20% 2g/10mL, Para-aminohippurate
PAH (Basic Pharma, Geleen, Netherlands) has been used to measure ERPF in human research for 7 decades, and is very well tolerated and generally recognized as safe with low toxicity.
Iohexol Inj 300 MG/ML Diagnostic aid/agent used to measure glomerular filtration rate (GFR)Drug
Also called omnipaque 300
Iohexol (Omnipaque 300, GE Healthcare, Chicago, IL) is a nonionic, low osmolar contrast agent with a history of extensive use in Radiology practice (for contrast x-rays) that shares many qualities of an ideal GFR marker, like inulin, such as not being absorbed, metabolized, or secreted by the kidney.
| Study group | Role | What they receive |
|---|---|---|
| PANDA, T1D | New participants with T1D will be enrolled at the University of Colorado and University of Washington. | |
| PANDA Sub Study, Former CROCODILE Participants | Participants will be enrolled from the existing CROCODILE study (COMIRB # 19-1282), adding longitudinal follow-up to completed kidney biopsies and baseline data and biosample acquisition. Receives: Drug: Aminohippurate Sodium Inj 20% Diagnostic aid/agent used to measure effective renal plasma flow (ERPF); Drug: Iohexol Inj 300 MG/ML Diagnostic aid/agent used to measure glomerular filtration rate (GFR) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal Oxygenation
Blood oxygen level dependent (BOLD) MRI
Measured: 30 min
Renal Perfusion
Arterial Spin Labeling (ASL) MRI
Measured: 30 min
Insulin Sensitivity
Hyperinsulinemic-Euglycemic Clamp
Measured: 4.5 hours
Secondary outcomes (2)
Glomerular Filtration Rate (GFR)
Iohexol Clearance Study
Measured: 3 hours
Effective Renal Plasma Flow (ERPF)
PAH Clearance Study
Measured: 2.5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2022
- Study start9 Mar 2022
- Primary completion30 Jun 2027 (estimated)
- Study completion31 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 1 DiabetesStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05319990
- Sponsor's protocol ID
- 22-0250
- Acronym
- PANDA
- Status last verified
- May 2026
- First submitted
- 1 Apr 2022
- Last updated
- 22 May 2026
- 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 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pathogenesis of Kidney Disease in Type 1 Diabetes: a Modern Kidney Biopsy Cohort (The PANDA Study)
- ClinicalTrials.gov ID
- NCT05319990
- Acronym / sponsor ID
- PANDA / 22-0250
- Conditions
- Type 1 Diabetes, Diabetic Kidney Disease, Diabetes Complications, Diabetic Nephropathies, Autoimmune Diabetes
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 9 Mar 2022 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 11 Apr 2022 (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.
Diabetic kidney disease (DKD) occurs in up to 40% of people with type 1 diabetes (T1D), often leading to kidney failure and markedly magnifying risks of cardiovascular disease and premature death. Landmark T1D kidney biopsy studies identified the classic pathological lesions of DKD, which have been attributed largely to hyperglycemia. Recent advances in continuous glucose monitoring (CGM) and automated insulin delivery have facilitated improved glycemic control, but the residual risk of DKD continues to be high. In addition, obesity and insulin resistance (IR) have accompanied intensive glycemic therapy and may promote mitochondrial dysfunction and inflammation. Deciphering the molecular underpinnings of DKD in modern-day T1D and identifying modifiable risk factors could lead to more effective and targeted therapies to prevent DKD.
Detailed description
The overall goal of this project is to characterize the molecular, morphometric, and metabolic features of DKD over the modern clinical course of T1D. The investigators hypothesize that perturbed kidney energetics and hypoxia are central metabolic pathways in the development of DKD. Kidney hypoxia stems from a mismatch between increased renal energy demand (e.g., increased glomerular filtration rate [GFR] and tubular reabsorption of sodium) and impaired substrate metabolism (e.g., IR and mitochondrial dysfunction) and results in activation of the hypoxia-inducible factor (HIF) system. Although upregulation of HIF1α confers favorable short-term effects, sustained activation promotes cellular injury. Supporting these hypotheses, data from our group and others have shown that obesity, IR, and The investigators also found that youth with T1D exhibit kidney hypoxia by MRI that strongly associates with IR and mitochondrial dysfunction. Moreover, our preliminary single-cell RNA sequencing (scRNA-seq) data from kidney biopsies demonstrate upregulated tubular expression of HIF1α in adults with T1D vs. healthy controls. The investigators propose to build a unique new longitudinal kidney biopsy cohort (N=100) spanning the critical duration of T1D over which DKD initiates and progresses (5-30 years). Participants will be enrolled from our existing CROCODILE study (adding longitudinal follow-up to completed kidney biopsies and baseline data and biosample acquisition) and from new enrollment at the University of Colorado and University of Washington. Normative kidney biopsy data will be provided from our existing cohort of healthy controls (N=20) and the Kidney Precision Medicine Project (KPMP). The investigators will implement state-of-the-art molecular (scRNA-seq) and morphometric interrogation of kidney tissue and rigorous metabolic phenotyping to include kidney magnetic resonance imaging (MRI), direct measurements of glycemia (continuous glucose monitoring), intraabdominal fat (dual-energy X-ray absorptiometry), estimation of insulin sensitivity by a T1D-validated equation, and (in a subset) GFR (iohexol clearance) and renal plasma flow (p-aminohippurate clearance). Participants will be followed longitudinally for DKD outcomes. A subset of 20 participants will undergo repeat kidney biopsies and associated procedures 3 years after baseline kidney biopsy.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PANDA, T1D | – | –New participants with T1D will be enrolled at the University of Colorado and University of Washington. |
| PANDA Sub Study, Former CROCODILE Participants | – | Drug: Aminohippurate Sodium Inj 20% Diagnostic aid/agent used to measure effective renal plasma flow (ERPF), Drug: Iohexol Inj 300 MG/ML Diagnostic aid/agent used to measure glomerular filtration rate (GFR)Participants will be enrolled from the existing CROCODILE study (COMIRB # 19-1282), adding longitudinal follow-up to completed kidney biopsies and baseline data and biosample acquisition. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The investigators propose to address the specific aims of this study in a cross-sectional project with 70 newly enrolled adults with T1D and 30 former CROCODILE participants (COMIRB #19-1282).
Key inclusion criteria (3 listed)
- Age ≥ 18 years at enrollment (rationale: this study focuses on determinants of early DKD over the course of T1D in adults)
- T1D duration >5 years (rationale: DKD in T1D rarely manifests prior to 5 years of disease duration)
- HbA1c <11% (rationale: HbA1c ≥ 11% exceeds the average HbA1c at most academic center and would limiting the generalizability of our study findings)
Key exclusion criteria (18 listed)
- T2D and monogenic diabetes (rationale: our study focuses on T1D)
- Recent diabetic ketoacidosis, i.e., <1 month (rationale: safety and insulin resistance and tubular dysfunction of DKA can confound study findings)
- eGFR < 30 ml/min/1.73m2 or dialysis treatment (rationale: to reduce the likelihood of identifying secondary pathways that are not specific to kidney injury from T1D)
- Kidney transplant recipients (rationale: molecular confounding from immunosuppression)
- Kidney biopsy contraindications (rationale: safety - kidney biopsy):
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% Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)Also: Sodium 4-amino hippurate (PAH) inj 20% 2g/10mL, Para-aminohippuratePAH (Basic Pharma, Geleen, Netherlands) has been used to measure ERPF in human research for 7 decades, and is very well tolerated and generally recognized as safe with low toxicity. | Drug | PANDA Sub Study, Former CROCODILE Participants |
| Iohexol Inj 300 MG/ML Diagnostic aid/agent used to measure glomerular filtration rate (GFR)Also: omnipaque 300Iohexol (Omnipaque 300, GE Healthcare, Chicago, IL) is a nonionic, low osmolar contrast agent with a history of extensive use in Radiology practice (for contrast x-rays) that shares many qualities of an ideal GFR marker, like inulin, such as not being absorbed, metabolized, or secreted by the kidney. | Drug | PANDA Sub Study, Former CROCODILE Participants |
Primary outcome
Renal Oxygenation
Time frame: 30 min
Blood oxygen level dependent (BOLD) MRI
Renal Perfusion
Time frame: 30 min
Arterial Spin Labeling (ASL) MRI
Insulin Sensitivity
Time frame: 4.5 hours
Hyperinsulinemic-Euglycemic Clamp
2 secondary outcomes
Glomerular Filtration Rate (GFR)
Time frame: 3 hours
Effective Renal Plasma Flow (ERPF)
Time frame: 2.5 hours
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 22 May 2026.
- 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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 1 Diabetes and Diabetic Kidney Disease, 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 3 inclusion and 18 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: under way, not looking for participants, as of the sponsor's last update on 22 May 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.
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?
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?
Renal Oxygenation (time frame: 30 min). The study lists 3 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 22 May 2026.