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

Recruiting

• Conditions: Proteinuria; Nephropathy; Type 2 Diabetes; Stress

• Registration Number: NCT02818192
• Lead Sponsor: University of Manitoba

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 500 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-06-27
• Study First Submitted QC: 2016-06-28
• Study First Posted: 2016-06-29
• Study Start: 2017-01
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-05
• Last Update Posted: 2024-06-07
• Primary Completion: 2026-03
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

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) or
   • Hemoglobin A1c value ≥ 6.5%

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Persistent Albuminuria	2 years	Persistent albuminuria; Definition: 1. Albumin:creatine (ACR) \> 3.0mg/mmol in at least two urine samples within 6 months at least 1 month apart.; 2. ACR \> 3.0mg/mmol with a timed overnight urine or first am urine collection.
Change in albumin excretion over time.	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.

Secondary Outcome Measures

Name	Time	Method
Change in estimated glomerular filtration rate (eGFR) over time.	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 iCARE equation. This equation was previously validated for use in the iCARE cohort.

Trial Locations

Locations (1)

Children's Hospital Research Institute of Manitoba/University of Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada