Diabetic NephropathiesNCT04029402
Molecular Analysis of Diabetic Kidney Disease Biopsies
An observational study of Diabetic Nephropathies and Kidney Disease, Chronic, run by Unity Health Toronto at 4 sites in Canada.
Trial summary
Despite decades of research, the pathogenesis of human diabetic kidney disease remains largely unclear. Our goal is to use archived human kidney biopsy tissue from patients with and with diabetic nephropathy to identify new molecules that drive and/or protect against disease progression. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Nephropathies, Kidney Disease, Chronic
- What is being tested?
- RNA sequencing
- How many people
- 500 participants
- Where
- 4 sitesCanada
- Study dates
- 1 Jul 2019to Dec 2025
- Phase
- Observational
- 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 18 years and older
- All sexes
- Adult, Older adult
Study population: 1. Cases: A group of patients with diabetic kidney disease 2. Controls: A group of healthy control patients
Who may be able to join
- history of type 1 or type 2 diabetes
- at least 1 archived native kidney biopsy that demonstrates either pure diabetic kidney disease or features of non-specific vascular disease, including glomerulosclerosis, non-inflammatory vascular disease,
- sufficient remaining archived kidney biopsy tissue for RNA sequencing (100 um thick tissue section) and histologic analysis (PAS and Masson Trichrome staining)
- at least 1 native kidney disease biopsy with no diagnostic abnormality
Who cannot join
- less than 3 eGFR values post-biopsy
- latest recorded eGFR values less than 6 months post-biopsy
Trial locations and contacts
4 sites in 1 country.
Canada4 sites, 4 recruiting
- Not yet recruiting
University of Ottawa
Ottawa, Ontario
Kevin Burns, MD
- Recruiting
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
Michelle Nash, 416-864-6060 ext. 3692, nashm@smh.ca
- Not yet recruiting
University of British Columbia
Vancouver, British Columbia
Sean Barbour, MD
- Not yet recruiting
University of Manitoba
Winnipeg, Manitoba
Claudio Rigatto, MD
About this study
Despite decades of research, the pathogenesis of human diabetic kidney disease remains largely unclear. Our goal is to use archived human kidney biopsy tissue from patients with and with diabetic nephropathy to identify new molecules that drive and/or protect against disease progression. We will use RNA sequencing to identify transcriptomic changes that associate with histologic and functional outcomes.
Read the detailed description
RESEARCH OBJECTIVES A. To identify differences in transcription profiles obtained from residual kidney tissue which was obtained for clinical purposes.
- To identify differences in transcription profile between patients whose loss of kidney function progresses rapidly (eGFR decline ≥4ml/min/year) and in whom it progresses more slowly (eGFR decline <4ml/min/year).
- To identify differences in transcription profile between predominantly glomerular and predominantly tubulointerstitial histopathological types .
- To identify new pathogenetic pathways that may become targets for therapeutic intervention
METHODS The planned study centres on the use of archival biopsy material that is superfluous to what is or would be needed for clinical care (01/01/1995 to 31/05/2018 , n= approximately 400-500). Archived samples will be collected from St. Michael's Hospital and a number of collaborating centres, including but not limited to University of British Columbia, the University of Manitoba, and the University of Ottawa.
RNA will be extracted from the biopsy material using either the core that has been used for immunofluorescence microscopy and is stored at -80˚C, and/or the core that is formalin-fixed, embedded in paraffin wax and stored at room temperature. The RNA thereby extracted will be subjected to detailed interrogation by RNASeq to quantify the expression level of mRNAs (transcriptome) and compare differences, as indicated in the research objectives detailed above. The transcriptome will then be related to the clinical course (eGFR decline) and histopathological changes, in addition to examining potentially pathogenetically important and that are amenable to therapeutic intervention.
Histopathology will also be performed and classified according to established systems.
Clinical information that would be retrieved from patients' medical records are listed below.
Clinical data
- Age
- Gender
- Ethnicity
- Diabetes history
- Diabetes type: 1, 2
- Retinopathy history
- Smoking history
- Medications
- Comorbidities
- Past medical history
- Primary nephrologist Laboratory data (prior to biopsy, at biopsy and post-biopsy)
- Renal function measures and calculations. For example:
- Serum creatinine, eGFR ii. Change in creatinine and eGFR iii. Urinary albumin:creatinine values and ratio (ACR) iv. Urine protein:creatinine values and ratio (PCR) v. Urinary protein excretion rate (UPEx) vi. Changes in ACR, PCR, UPEx
- Diabetes measures and calculations. Biopsy data
- Biopsy related data
Each site will locally maintain a confidential Master Linking Log.
De-identified data will be entered into a secure REDCap database that is hosted by St. Michael's Hospital.
- Conditions
- Diabetic Nephropathies, Kidney Disease, Chronic
- Being tested
- RNA sequencing
- Medical subject headings
- Diabetic Nephropathies, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RNA sequencingOther
Also called Histology, Slope of eGFR decline
Transcriptomic analysis of kidney biopsy tissue, and linking with slope of eGFR decline
| Study group | Role | What they receive |
|---|---|---|
| Diabetic kidney disease | Patients with archived biopsies with a pathologic diagnosis of diabetic kidney disease, interstitial fibrosis/tubular atrophy, or nephrosclerosis. Receives: Other: RNA sequencing | |
| Healthy controls | Potential living donors with archived biopsies performed as part of their donor workup and with no diagnostic abnormalities Receives: Other: RNA sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Interstitial fibrosis
Extent of interstitial fibrosis in kidney biopsy assessed using a semi-quantitative scale on light microscopy of biopsy sections
Measured: Baseline biopsy
Glomerulosclerosis
Extent of glomerulosclerosis in kidney biopsy assessed using a semi-quantitative scale on light microscopy of biopsy sections
Measured: Baseline biopsy
Renal function change
Slope of eGFR decline
Measured: Baseline biopsy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2019
- Study start1 Jul 2019
- Primary completionDec 2022 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic NephropathiesStudies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe 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
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- University of Ottawa, University of British Columbia, University of Manitoba
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04029402
- Sponsor's protocol ID
- 16-118
- Status last verified
- Apr 2021
- First submitted
- 21 Jul 2019
- Last updated
- 30 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Analysis of Diabetic Kidney Disease Biopsies
- ClinicalTrials.gov ID
- NCT04029402
- Acronym / sponsor ID
- 16-118
- Conditions
- Diabetic Nephropathies, Kidney Disease, Chronic
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Collaborators
- University of Ottawa, University of British Columbia, University of Manitoba
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 23 Jul 2019 (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.
Despite decades of research, the pathogenesis of human diabetic kidney disease remains largely unclear. Our goal is to use archived human kidney biopsy tissue from patients with and with diabetic nephropathy to identify new molecules that drive and/or protect against disease progression. We will use RNA sequencing to identify transcriptomic changes that associate with histologic and functional outcomes.
Detailed description
RESEARCH OBJECTIVES A. To identify differences in transcription profiles obtained from residual kidney tissue which was obtained for clinical purposes.
- To identify differences in transcription profile between patients whose loss of kidney function progresses rapidly (eGFR decline ≥4ml/min/year) and in whom it progresses more slowly (eGFR decline <4ml/min/year).
- To identify differences in transcription profile between predominantly glomerular and predominantly tubulointerstitial histopathological types .
- To identify new pathogenetic pathways that may become targets for therapeutic intervention
METHODS The planned study centres on the use of archival biopsy material that is superfluous to what is or would be needed for clinical care (01/01/1995 to 31/05/2018 , n= approximately 400-500). Archived samples will be collected from St. Michael's Hospital and a number of collaborating centres, including but not limited to University of British Columbia, the University of Manitoba, and the University of Ottawa.
RNA will be extracted from the biopsy material using either the core that has been used for immunofluorescence microscopy and is stored at -80˚C, and/or the core that is formalin-fixed, embedded in paraffin wax and stored at room temperature. The RNA thereby extracted will be subjected to detailed interrogation by RNASeq to quantify the expression level of mRNAs (transcriptome) and compare differences, as indicated in the research objectives detailed above. The transcriptome will then be related to the clinical course (eGFR decline) and histopathological changes, in addition to examining potentially pathogenetically important and that are amenable to therapeutic intervention.
Histopathology will also be performed and classified according to established systems.
Clinical information that would be retrieved from patients' medical records are listed below.
Clinical data
- Age
- Gender
- Ethnicity
- Diabetes history
- Diabetes type: 1, 2
- Retinopathy history
- Smoking history
- Medications
- Comorbidities
- Past medical history
- Primary nephrologist Laboratory data (prior to biopsy, at biopsy and post-biopsy)
- Renal function measures and calculations. For example:
- Serum creatinine, eGFR ii. Change in creatinine and eGFR iii. Urinary albumin:creatinine values and ratio (ACR) iv. Urine protein:creatinine values and ratio (PCR) v. Urinary protein excretion rate (UPEx) vi. Changes in ACR, PCR, UPEx
- Diabetes measures and calculations. Biopsy data
- Biopsy related data
Each site will locally maintain a confidential Master Linking Log.
De-identified data will be entered into a secure REDCap database that is hosted by St. Michael's Hospital.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diabetic kidney disease | – | Other: RNA sequencingPatients with archived biopsies with a pathologic diagnosis of diabetic kidney disease, interstitial fibrosis/tubular atrophy, or nephrosclerosis. |
| Healthy controls | – | Other: RNA sequencingPotential living donors with archived biopsies performed as part of their donor workup and with no diagnostic abnormalities |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- 1. Cases: A group of patients with diabetic kidney disease 2. Controls: A group of healthy control patients
Key inclusion criteria (4 listed)
- history of type 1 or type 2 diabetes
- at least 1 archived native kidney biopsy that demonstrates either pure diabetic kidney disease or features of non-specific vascular disease, including glomerulosclerosis, non-inflammatory vascular disease,
- sufficient remaining archived kidney biopsy tissue for RNA sequencing (100 um thick tissue section) and histologic analysis (PAS and Masson Trichrome staining)
- at least 1 native kidney disease biopsy with no diagnostic abnormality
Key exclusion criteria (2 listed)
- less than 3 eGFR values post-biopsy
- latest recorded eGFR values less than 6 months post-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 |
|---|---|---|
| RNA sequencingAlso: Histology, Slope of eGFR declineTranscriptomic analysis of kidney biopsy tissue, and linking with slope of eGFR decline | Other | Diabetic kidney disease, Healthy controls |
Primary outcome
Interstitial fibrosis
Time frame: Baseline biopsy
Extent of interstitial fibrosis in kidney biopsy assessed using a semi-quantitative scale on light microscopy of biopsy sections
Glomerulosclerosis
Time frame: Baseline biopsy
Extent of glomerulosclerosis in kidney biopsy assessed using a semi-quantitative scale on light microscopy of biopsy sections
Renal function change
Time frame: Baseline biopsy
Slope of eGFR decline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2021.
- Individual participant dataSharing planned: No
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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.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetic Nephropathies and Kidney Disease, Chronic, run by Unity Health Toronto at 4 sites in Canada.
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 2 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: status not confirmed, as of the sponsor's last update on 30 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Richard Gilbert, MD PhD (416-864-3747, richard.gilbert@utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Interstitial fibrosis (time frame: Baseline biopsy). 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 30 Apr 2021.