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Improving Renal Complications in Adolescents With Type 2 Diabetes Through REsearch Cohort Study (National iCARE Study) (iCARE)

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ClinicalTrials.gov Identifier: NCT02818192
Recruitment Status : Recruiting
First Posted : June 29, 2016
Last Update Posted : November 4, 2020
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Dr. Brandy Wicklow, University of Manitoba

Tracking Information
First Submitted Date June 27, 2016
First Posted Date June 29, 2016
Last Update Posted Date November 4, 2020
Actual Study Start Date January 2017
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 29, 2016)
  • Persistent Albuminuria [ Time Frame: 2 years ]
    Persistent albuminuria Definition:
    1. Albumin:creatine (ACR) > 2.0mg/mmol in at least two urine samples within 6 months at least 1 month apart.
    2. ACR > 2.0mg/mmol with a timed overnight urine or first am urine collection.
  • Change in albumin excretion over time. [ Time Frame: 2 years ]
    Change in albumin excretion over 2 years. The change in albumin:creatinine ratio, treated as a continuous outcome measure was selected as a valid evaluation of progression of renal injury over time.
Original Primary Outcome Measures
 (submitted: June 28, 2016)
  • Persistent Albuminuria [ Time Frame: 2 years ]
    Persistent albuminuria Definition:
    1. Albumin:creatine (ACR) > 2.0mg/mmol in at least two urine samples within 6 months at least 1 month apart 72. (generally done as part of standard clinical care prior to enrollment)
    2. ACR > 2.0mg/mmol with a timed overnight urine or first am urine collection. This urine will be done in coordination of baseline visit. The ACR from this collection will be utilized in the analysis.
  • Change in albumin excretion over time. [ Time Frame: 2 years ]
    Change in albumin excretion over 2 years. The change in albumin:creatinine ratio, treated as a continuous outcome measure was selected as a valid evaluation of progression of renal injury over time.
Change History
Current Secondary Outcome Measures
 (submitted: June 29, 2016)
Change in estimated glomerular filtration rate (eGFR) over time. [ Time Frame: 2 years ]
This outcome will be exploratory as significant changes are not expected during a 2-year follow-up period. However, as GFR reflects actual kidney function, this outcome will become increasingly important as chronic kidney disease (CKD) progresses in the cohort over time. GFR will be determined with serum creatinine measurements, utilizing a new eGFR formula for overweight youth, which have been validated utilizing iohexol GFR data from the initial cohort. eGFR will be calculated with the pediatric Schwartz formula and iCARE equation. This equation was previously validated for use in the iCARE cohort.
Original Secondary Outcome Measures
 (submitted: June 28, 2016)
Change in estimated glomerular filtration rate (eGFR) over time. [ Time Frame: 2 years ]
This will be exploratory as we do not expect significant changes during a 2-year follow-up period. However, as GFR reflects actual kidney function, this outcome will become increasingly important as chronic kidney disease (CKD) progresses in the cohort over time. GFR will be determined with serum creatinine measurements, utilizing a new eGFR formula for overweight youth, which we have validated utilizing iohexol GFR data from the initial cohort. eGFR will be calculated with the pediatric Schwartz formula and iCARE equation. This equation was previously validated for use in the iCARE cohort.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Improving Renal Complications in Adolescents With Type 2 Diabetes Through REsearch Cohort Study (National iCARE Study)
Official Title Improving Renal Complications in Adolescents With Type 2 Diabetes Through REsearch Cohort Study (National iCARE Study)
Brief Summary

The overall aim of the project is to elucidate the primary bio-psycho-social (BPS) risk factors for albuminuria in youth with type 2 diabetes (T2D) and the mechanisms by which they cause renal injury. The Study Aims include:

  1. Characterize the primary BPS risk factors associated with prevalent and progressive albuminuria in youth with T2D.
  2. Determine individual, family and community level factors that influence biological and psychological risk factors and behaviors (adherence) that could be modified to protect against prevalent and progressive albuminuria.
  3. Determine if systemic and renal inflammation is the common pathway through which BPS risk factors lead to albuminuria in youth with T2D.

Study Hypotheses include:

  1. Biological factors (poor glycemic control and systolic ambulatory hypertension), and psychological and social adversity (stress, mental distress and poverty) are significant predictors of prevalent and progressive albuminuria in youth with T2D.
  2. Community and family support will be negatively associated with stress, and a lower risk of both prevalent and progressive albuminuria.
  3. Systemic and renal inflammation is the common pathway through which BPS risk factors lead to albuminuria in youth with T2D.
Detailed Description The investigators will conduct a case-control study within a two-year, prospective observational cohort study of 400 prevalent cases of T2D diagnosed <18 years of age. The investigators will evaluate the primary BPS risk factors associated with prevalent albuminuria using a principal component analysis (PCA) of associations between primary exposure variables at enrollment. After confirming the relevant BPS factors in the PCA analysis, the investigators will utilize a structural equation modeling approach to confirm the developed model.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Serum, plasma, random urine and buffy coat for DNA extraction will be collected at the baseline visit on all recruited patients that consent to biobanking such that future ancillary studies can be performed. Samples will be processed and frozen at -80 °C, and will be stored for up to 25 years with participant consent. Tests that may be run on stored samples include metabolomics, peptidomics, proteomics, and podocyte microparticle analyses should additional funding be obtained. Samples will be collected at each site and frozen. Periodically samples will be sent to the Canadian Biosample Repository at the University of Alberta for long term storage.
Sampling Method Non-Probability Sample
Study Population Prevalent youth 10-18 years of age being treated for T2D at 9 pediatric endocrinology clinics across Canada (B.C. Children's in Vancouver, Stollery Hospital in Edmonton, Alberta Children's Hospital in Calgary, Children's Hospital of Winnipeg, McMaster Children's Hospital in Hamilton, Children's Hospital of Eastern Ontario in Ottawa, SickKids Hospital in Toronto, McGill University Health Centre in Montreal and the IWK Health Centre in Halifax)
Condition
  • Type 2 Diabetes
  • Proteinuria
  • Stress
  • Nephropathy
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Dart AB, Wicklow BA, Sellers EA, Dean HJ, Malik S, Walker J, Chateau D, Blydt-Hansen TD, McGavock JM; iCARE investigators. The Improving Renal Complications in Adolescents With Type 2 Diabetes Through the REsearch (iCARE) Cohort Study: rationale and Protocol. Can J Diabetes. 2014 Oct;38(5):349-55. doi: 10.1016/j.jcjd.2014.07.224. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: June 28, 2016)
400
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • All youth with T2D that do not meet exclusion criteria are eligible for the study.

Criteria for Diagnosis of T2D:

  1. Diagnosis of diabetes will be made according to the Canadian Diabetes Association criteria. There must be 2 abnormal blood glucose tests on different days OR 1 abnormal blood glucose test + symptoms of diabetes:

    • Fasting plasma glucose of > 7.0 mmol/L or
    • Random glucose > 11.1mmol/L or
    • 2 hour glucose > 11.1 mmol/L after a standard oral glucose tolerance test (75g).
  2. Distinguishing T2D from type 1 diabetes (T1D) will be based on clinical risk factors including:

    • Presence of overweight/obesity,
    • Other evidence of insulin resistance (acanthosis nigricans)
    • Family history of type 2 diabetes (1st degree relative)
    • Intrauterine exposure to hyperglycemia,
    • Family heritage from a high-risk ethnic group (Indigenous, Hispanic, South Asian, Asian or African descent)
    • Absence of diabetes associated auto-antibodies
    • HNF-1 alpha heterozygote or homozygote

Exclusion Criteria:

  1. Diabetes secondary to medication use or surgery
  2. Antibodies suggestive of type 1 diabetes
  3. Current treatment with oral steroids or immunosuppressive agents as they may interfere with cortisol assessment and inflammatory markers
  4. Ever cancer
  5. Other chronic illness associated with systemic inflammation (ex. Juvenile rheumatoid arthritis, Crohns disease)
  6. Patient and or caregiver unable or unwilling to provide voluntary informed assent/consent
Sex/Gender
Sexes Eligible for Study: All
Ages 10 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Brandy A Wicklow, MD, MSc 2047871222 bwicklow@hsc.mb.ca
Contact: Melissa Gabbs, MSc 2047893827 MGabbs@chrim.ca
Listed Location Countries Canada
Removed Location Countries  
 
Administrative Information
NCT Number NCT02818192
Other Study ID Numbers B2011:024
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Undecided
Plan Description: This is a multi-site trial where the use and compilation of individual level data is being discussed amongst the various ethics boards across Canada.
Responsible Party Dr. Brandy Wicklow, University of Manitoba
Study Sponsor University of Manitoba
Collaborators Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Brandy A Wicklow, MD, MSc University of Manitoba, Children's Hospital Research Institute of Manitoba
PRS Account University of Manitoba
Verification Date November 2020