Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Novel Biomarker for Development of T2D

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02326129
Recruitment Status : Recruiting
First Posted : December 25, 2014
Last Update Posted : December 25, 2018
Sponsor:
Collaborators:
Children's Miracle Network
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date December 22, 2014
First Posted Date December 25, 2014
Last Update Posted Date December 25, 2018
Study Start Date February 2015
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 31, 2017)
  • Relationship between 11β-HSD1 and 5α-reductase activity, and measures of insulin resistance [ Time Frame: Two year ]
    To assess the relationship between 11β-HSD1 and 5α-reductase activity, and measures of insulin resistance in a cohort of obese children with varying degrees of insulin resistance and glucose intolerance
  • Gender and pubertal status [ Time Frame: Two year ]
    Investigate the role of gender and pubertal status on 11β-HSD1 and 5α-reductase activity
  • Compare 11β-HSD1 activity and 5α-reductase activity among obese adolescents with T2D, obese adolescents without T2D and normal weight controls [ Time Frame: Two year ]
    The investigators hypothesize that obese adolescents with T2D will have the highest levels of 11β-HSD1 activity followed by the obese adolescents with insulin resistance, followed by obese subjects with normal insulin sensitivity. Normal weight control group will have the lowest levels.
Original Primary Outcome Measures
 (submitted: December 22, 2014)
  • Relationship between 11β-HSD1 and 5α-reductase activity, and measures of insulin resistance [ Time Frame: One year ]
    To assess the relationship between 11β-HSD1 and 5α-reductase activity, and measures of insulin resistance in a cohort of obese children with varying degrees of insulin resistance and glucose intolerance
  • Gender and pubertal status [ Time Frame: One year ]
    We want to investigate the role of gender and pubertal status on 11β-HSD1 and 5α-reductase activity
  • Compare 11β-HSD1 activity and 5α-reductase activity among obese adolescents with T2D, obese adolescents without T2D and normal weight controls [ Time Frame: One year ]
    We hypothesize that obese adolescents with T2D will have the highest levels of 11β-HSD1 activity followed by the obese adolescents with insulin resistance, followed by obese subjects with normal insulin sensitivity. Normal weight control group will have the lowest levels.
Change History Complete list of historical versions of study NCT02326129 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: January 31, 2017)
  • Relationship between 11β-HSD1 and 5α-reductase activity, and key metabolic signatures associated with insulin resistance [ Time Frame: Two year ]
    The investigators hypothesize that 11β-HSD1 activity will be positively associated, and 5α-reductase activity negatively associated, with key metabolic signatures associated with insulin resistance.
  • Urine metabolic signatures associated with insulin resistance and type 2 diabetes [ Time Frame: Two year ]
    The investigators would like to validate if urine metabolomic profiling can be used for identifying key metabolomic signatures associated with insulin resistance
  • Spot urine for metabolic profiling [ Time Frame: Two year ]
    The investigators hypothesize that they will identify the same key metabolomic signatures associated with insulin resistance in obese adolescents with T2D compared to obese adolescents without T2D, and normal weight control group in spot fasting am urine samples.
Original Secondary Outcome Measures
 (submitted: December 22, 2014)
  • Relationship between 11β-HSD1 and 5α-reductase activity, and key metabolic signatures associated with insulin resistance [ Time Frame: One year ]
    We hypothesize that 11β-HSD1 activity will be positively associated, and 5α-reductase activity negatively associated, with key metabolic signatures associated with insulin resistance.
  • Urine metabolic signatures associated with insulin resistance and type 2 diabetes [ Time Frame: One year ]
    We would like to validate if urine metabolomic profiling can be used for identifying key metabolomic signatures associated with insulin resistance
  • Spot urine for metabolic profiling [ Time Frame: One year ]
    We hypothesize that we will identify the same key metabolomic signatures associated with insulin resistance in obese adolescents with T2D compared to obese adolescents without T2D, and normal weight control group in spot fasting am urine samples.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Novel Biomarker for Development of T2D
Official Title A Novel Biomarker for Development of Type 2 Diabetes: 11Beta-Hydroxy Steroid Dehydrogenase Type 1 Activity
Brief Summary The investigators wants to determine if 11β-HSD1 activity will be positively associated, and 5α-reductase activity negatively associated, with (a) degree of insulin resistance defined by the homeostatic model assessment of insulin resistance index (HOMA-IR) and (b) worsening glycemic control defined by higher HbA1c and impaired fasting glucose in a group of obese children and young adults with or without type 2 diabetes compared to lean children and young adults without diabetes. The investigators also want to identify key metabolic signatures associated with diabetes using metabolomic profiling.
Detailed Description

The overarching hypothesis is that increases in whole body 11β-HSD1 activity precede and presage the development of type 2 diabetes (T2D) in high-risk obese adolescents, serving as a critical determinant of insulin resistance and glucose intolerance. The increase in 11β-HSD1 activity, in combination with decreases in 5α-reductase activity, will increase tissue cortisol production, promoting the development of insulin resistance and the metabolic syndrome and predisposing to T2D. The investigators predict that increases in 11β-HSD1 activity will be detected in obese children prior to the development of insulin resistance and glucose intolerance and that the progressive increases in 11β-HSD1 will correlate with progressive decreases in insulin sensitivity and glucose tolerance. Given preliminary findings, the investigators also predict that increases in 11β-HSD1 will be greater and occur earlier in development in males than females. This could establish 11β-HSD1 activity as a novel, non-invasive biomarker for progression to, or for development of, glucose intolerance and T2D.

The identification of 11β-HSD1 as a biomarker that predicts T2D would have critical clinical import, allowing us to identify obese children and adults at highest risk of metabolic decompensation. Studies of 11β-HSD1 in obese subjects with varying degrees of IR and glucose intolerance will also narrow critical gaps in the understanding of the pathogenesis of T2D.

The investigators would like to also validate if urine metabolomic profiling can be used for identifying key metabolomic signatures associated with insulin resistance. To that end the investigators would like to examine detailed metabolomic profiles in 24 hour and spot urine samples.

The study population will include 50 obese adolescents with T2D, 50 obese adolescents without T2D and 50 age, gender, race and pubertal status-matched normal weight controls. The subjects will be recruited at the Healthy Lifestyle Program at Duke, Diabetes Clinics at Lenox Baker Children's Hospital and Roxboro Clinics.

Study activities include physical exam and medical history, vitals, laboratory tests (only for obese adolescents), urine testing for sugar (only for normal weight adolescents), 24 hour urine collection, spot urine collection, body fat content measurement, and food and activity questionnaire.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
24 hour urine samples.
Sampling Method Non-Probability Sample
Study Population The study population will include 50 obese adolescents with Type II Diabetes, 50 obese adolescents without Type II Diabetes, and age, gender, race and pubertal status-matched normal weight controls.
Condition Diabetes Type II
Intervention Not Provided
Study Groups/Cohorts
  • Obese with Type 2 Diabetes
    Obese adolescents with Type 2 Diabetes
  • Obese without Type 2 Diabetes
    Obese adolescents without Type 2 Diabetes
  • Normal weight
    Normal weight adolescents
Publications * Not Provided

*   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: January 31, 2017)
150
Original Estimated Enrollment
 (submitted: December 22, 2014)
75
Estimated Study Completion Date June 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  1. Obese/Overweight adolescents without T2D who are having their first visit to the Healthy Lifestyle Program at Duke
  2. Obese/Overweight adolescents with T2D followed at Diabetes Clinics at Lenox Baker Children's Hospital
  3. Age, gender, race and pubertal status matched normal weight adolescents presenting for "well child check" at Roxboro Clinics
  4. ≥12 to 18 (inclusive) years of age
  5. Both the subject and one parent/guardian present will need to be able to speak and read English

Exclusion Criteria:

  1. Currently or within the past month taken systemic corticosteroids, antipsychotics, medications for weight loss, topiramate, oral contraceptives or medroxy-progesterone acetate
  2. Children with genetic syndrome causing obesity
  3. Children with decompensated hypothyroidism
  4. Normal weight children with glucosuria as this might indicate undiagnosed diabetes
  5. Children that are pregnant
Sex/Gender
Sexes Eligible for Study: All
Ages 12 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Pinar Gumus Balikcioglu, M.D. 9196684002 pinar.gumus@duke.edu
Contact: Denise Simmons, BS 9193237601 denise.f.simmons@duke.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02326129
Other Study ID Numbers Pro00057460
K23DK117067 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Duke University
Study Sponsor Duke University
Collaborators
  • Children's Miracle Network
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Pinar Gumus Balikcioglu, M.D. Pediatric Endocrinology
PRS Account Duke University
Verification Date December 2018