Clinical trial NCT02818192: 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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Type 2 Diabetes
Proteinuria
Stress
Nephropathy
Lead sponsor: University of Manitoba
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2016-06-29
Enrollment: 500
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Prevalent youth 10-18 years of age being treated for T2D at 7 pediatric endocrinology clinics across Canada (Stollery Hospital in Edmonton, Alberta Children's Hospital in Calgary, Children's Hospital of Saskatoon, Children's Hospital of Winnipeg, Children's Hospital of Eastern Ontario in Ottawa, SickKids Hospital in Toronto, and the IWK Health Centre in Halifax)

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.

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) 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

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

Primary outcomes:
measure: Persistent Albuminuria
timeFrame: 2 years
measure: Change in albumin excretion over time.
timeFrame: 2 years
Secondary outcomes:
measure: Change in estimated glomerular filtration rate (eGFR) over time.
timeFrame: 2 years
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: Children's Hospital Research Institute of Manitoba/University of Manitoba
state: Manitoba
Study officials:
affiliation: University of Manitoba, Children's Hospital Research Institute of Manitoba
name: Brandy A Wicklow, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.