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Diabetic Kidney Alarm (DKA) Study (DKA)

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ClinicalTrials.gov Identifier: NCT03128229
Recruitment Status : Recruiting
First Posted : April 25, 2017
Last Update Posted : November 6, 2017
Sponsor:
Collaborator:
Thrasher Research Fund
Information provided by (Responsible Party):
Petter Bjornstad, University of Colorado Denver School of Medicine Barbara Davis Center

Brief Summary:
The overarching goals of this study are to determine whether tubular dysfunction (elevated urine sodium, bicarbonate and amino acids) and injury (elevated kidney injury molecule 1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL] and matrix metallopeptidase 9 [MMP9]) exist in new onset diabetic ketoacidosis (age 3-18), whether it is reversible and whether it is related to uricosuria and copeptin. The investigators propose to study a cohort of youth (ages 3-18, n=40) with new onset T1D who have serum and urine collection at DKA diagnosis and 3-month follow-up.

Condition or disease
Type 1 Diabetes Mellitus Diabetic Ketoacidosis

Detailed Description:
Every year over 86,000 children (0-14 years) worldwide are diagnosed with type 1 diabetes (T1D) translating to a lifetime of exposure and risk for early death from cardiovascular disease (CVD) and diabetic kidney disease (DKD). DKD, which manifests in children and adolescents, remains the leading cause of renal failure and dialysis in the Western world (4). While diabetic glomerulopathy has received significant attention from researchers, determinants of tubular injury in diabetes are less well examined. Compared to glomerular injury, tubular injury is known to associate better with renal function. The majority of youth diagnosed with T1D in the US present with diabetic ketoacidosis (DKA), a condition associated with risks factors for tubular injury including dehydration, metabolic acidosis and acute glycemia. It is unknown whether DKA is associated with tubular injury. The investigators published the first report showing that youth with established T1D have more acidic urine and higher fractional excretion of uric acid (FeUA) than their non-diabetic peers, which may predispose to UUA-mediated tubulopathy. Furthermore, T1D is associated with vasopressin overactivity, and the investigators reported strong relationships between serum copeptin, a reliable surrogate marker for vasopressin, and DKD in T1D. The overarching goals of this study are to determine whether tubular dysfunction (elevated urine sodium, bicarbonate and amino acids) and injury (elevated KIM-1, NGAL and MMP9) exist in new onset DKA, whether it is reversible and whether it is related to uricosuria and copeptin. The investigators propose to study a cohort of youth (ages 3-18, n=40) with new onset T1D who have serum and urine collection at DKA diagnosis and 3-month follow-up.

Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Diabetic Kidney Alarm (DKA) Study - Tubulopathy in New Onset Diabetic Ketoacidosis
Actual Study Start Date : June 1, 2017
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Proximal tubular dysfunction [ Time Frame: At DKA (0-8 and 12-24 hours after starting IV insulin) ]
    Change in urine Na, HCO3 and amino acids concentrations

  2. Proximal tubular injury [ Time Frame: At DKA (0-8 and 12-24 hours after starting IV insulin) ]
    Change in urine and serum NGAL, KIM-1 and MMP9 concentrations


Secondary Outcome Measures :
  1. Proposed mediators of tubular dysfunction and injury [ Time Frame: At DKA (0-8 and 12-24 hours after starting IV insulin) ]
    Change in urine uric acid and serum fructose.

  2. Proposed mediators of tubular dysfunction and injury [ Time Frame: At DKA (0-8 hours after starting IV insulin) ]
    Presence of urine uric acid crystals by polarized microscopy

  3. Proposed mediators of tubular dysfunction and injury [ Time Frame: At DKA (12-24 hours after starting IV insulin) ]
    Presence of urine uric acid crystals by polarized microscopy


Biospecimen Retention:   Samples Without DNA
Serum and urine collection at 0-8h and 12-24h after starting IV insulin, and at 3 month follow-up.


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Ages Eligible for Study:   3 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Participants (3-18 years) with new onset T1D presenting with DKA will be recruited from the Emergency Department (ED) at Children's Hospital Colorado.
Criteria

Inclusion Criteria:

  • New onset T1D
  • DKA (mild, moderate and severe DKA eligible)
  • 3-17 years of age
  • Toilet trained
  • Boys and girls
  • All ethnicities
  • Initial presentation to Children's Hospital Colorado (CHCO) Main ED

Exclusion Criteria:

  • Known T1D
  • Non-T1D etiology
  • History of chronic kidney disease (eGFR <60ml/min/1.73m2) or dialysis dependent
  • History of tubulopathy (e.g. Fanconi syndrome)
  • Currently menstruating
  • Patient visiting Colorado with plan to establish diabetes care outside of Colorado
  • On ACE-inhibitors or angiotensin II-receptor blockers (ARB)
  • On sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03128229


Contacts
Contact: Petter Bjornstad, M.D. 7207774659 petter.bjornstad@childrenscolorado.org

Locations
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80238
Contact: Petter Bjornstad, M.D.         
Principal Investigator: Petter Bjornstad, M.D.         
Sub-Investigator: Kristen Nadeau, M.D.         
Sponsors and Collaborators
University of Colorado Denver School of Medicine Barbara Davis Center
Thrasher Research Fund

Publications:

Responsible Party: Petter Bjornstad, Pediatric Endocrinology Fellow, University of Colorado Denver School of Medicine Barbara Davis Center
ClinicalTrials.gov Identifier: NCT03128229     History of Changes
Other Study ID Numbers: 16-1403
First Posted: April 25, 2017    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Diabetic Ketoacidosis
Diabetes Mellitus
Diabetes Mellitus, Type 1
Ketosis
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Acidosis
Acid-Base Imbalance
Diabetes Complications