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Insulin Resistance in Adolescents

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ClinicalTrials.gov Identifier: NCT04089332
Recruitment Status : Recruiting
First Posted : September 13, 2019
Last Update Posted : November 11, 2019
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Tracking Information
First Submitted Date  ICMJE September 3, 2019
First Posted Date  ICMJE September 13, 2019
Last Update Posted Date November 11, 2019
Actual Study Start Date  ICMJE October 4, 2019
Estimated Primary Completion Date July 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 12, 2019)
  • Cognitive Function as determined by WASI (Verbal IQ) [ Time Frame: up to 1 day ]
    Participants will undergo a series of cognitive tests to evaluate intelligence, memory, speed function, executive function, and psychiatric quality of life. The results of these test will be scored and reported individually. The Wechsler Abbreviated Scale of Intelligence (WASI) for Verbal IQ is composed of 2 of the 4 WASI subtests: 31-item Vocabulary and 24-item Similarities. The total range of possible scores is 40-160; the higher the score, the higher the Verbal IQ.
  • Cognitive Function as determined by WASI (Performance IQ) [ Time Frame: up to 1 day ]
    Participants will undergo a series of cognitive tests to evaluate intelligence, memory, speed function, executive function, and psychiatric quality of life. The results of these test will be scored and reported individually. The Wechsler Abbreviated Scale of Intelligence (WASI) for Performance IQ is composed of 2 of the 4 WASI subtests: 13-item Block Design and 30-item Matrix Reasoning. The total range of possible scores is 40-160, the higher the score, the higher the Performance IQ.
  • Cognitive Function as determined by NIH Toolbox (List Learning) Test [ Time Frame: up to 1 day ]
    Participants will undergo a series of cognitive tests to evaluate intelligence, memory, speed function, executive function, and psychiatric quality of life. The results of these test will be scored and reported individually. The NIH Toolbox (List Learning) Test assesses working memory by having participants sort images by size order. The total range of possible score is 0-28, with higher scores indicating more improved working memory.
  • Cognitive Function as determined by NIH Toolbox (Oral Symbol Digit Test) [ Time Frame: up to 1 day ]
    Participants will undergo a series of cognitive tests to evaluate intelligence, memory, speed function, executive function, and psychiatric quality of life. The results of these test will be scored and reported individually. The NIH Toolbox (Oral Symbol Digit Test) assesses processing speed. The total range of possible scores is 0-144, the higher the score, the faster the processing speed.
  • Cognitive Function as determined by NIH Toolbox (Flanker Inhibitory Control and Attention) [ Time Frame: up to 1 day ]
    Participants will undergo a series of cognitive tests to evaluate intelligence, memory, speed function, executive function, and psychiatric quality of life. The results of these test will be scored and reported individually. The NIH Toolbox (Flanker Inhibitory Control and Attention) assess executive attention. It is a visual display using a central arrow flanked by arrows either pointing in the same direction or different that the central arrow. The participant is to indicate the direction of the central arrow when they are all pointing in the same direction. Scoring is algorithm derived and based on accuracy and reaction time, with a total range of possible scores 0-10 with higher scores indicating increased executive attention.
  • Cognitive Function as determined by NIH Toolbox (Pattern Completion) [ Time Frame: up to 1 day ]
    Participants will undergo a series of cognitive tests to evaluate intelligence, memory, speed function, executive function, and psychiatric quality of life. The results of these test will be scored and reported individually. The NIH Toolbox (Pattern Completion) assesses processing speed by asking participants to indicate if visual stimuli are the same or not the same. This test is scored by the total number of correct responses in 90 seconds (maximum score is 130). The higher the score, the better the processing speed.
  • Cognitive Function as determined by NIH Toolbox (Picture Sequence) [ Time Frame: up to 1 day ]
    Participants will undergo a series of cognitive tests to evaluate intelligence, memory, speed function, executive function, and psychiatric quality of life. The results of these test will be scored and reported individually. The NIH Toolbox (Picture Sequence) assesses episodic memory. Participants are shown a series of pictures one at a time, related to a single theme. After the last picture is shown, the participants is asked to place the pictures in the demonstrated sequence. The total number of correct placements across 3 trials provides the score, up to a maximum of 48. The higher the score, the better the episodic memory.
  • Cognitive Function as determined by WRAML (Picture Memory) [ Time Frame: up to 1 day ]
    Participants will undergo a series of cognitive tests to evaluate intelligence, memory, speed function, executive function, and psychiatric quality of life. The results of these test will be scored and reported individually. The Wide Range Assessment of Memory and Learning (WRAML) (Picture Memory Recognition) assesses visual memory function by asking participants to recall altered information from 4 pictures. Scoring is based on the number of correct items, up to a maximum of 51. The higher the score, the better the visual memory.
  • Cognitive Function as determined by D-KEFS (Color-Word Interference) [ Time Frame: up to 1 day ]
    Participants will undergo a series of cognitive tests to evaluate intelligence, memory, speed function, executive function, and psychiatric quality of life. The results of these test will be scored and reported individually. The Delis-Kaplan Executive Function System (D-KEFS) (Color-Word Interference) test assesses executive function and consists of 4 parts: color naming, word reading, inhibition, and inhibition/switching. Test performance is measured by completion time and errors on each part. Raw scores are converted to norm-referenced scaled scores adjusted for age and education. These scores are aligned with a population mean of 10, and standard deviation of 3. Higher scores indicate better executive function.
  • Cognitive Function as determined by D-KEFS (Trail Making Test) [ Time Frame: up to 1 day ]
    Participants will undergo a series of cognitive tests to evaluate intelligence, memory, speed function, executive function, and psychiatric quality of life. The results of these test will be scored and reported individually. The Delis-Kaplan Executive Function System (D-KEFS) (Trail Making Test) assesses executive function using visual scanning, number sequencing, letter sequencing, number-letter switching, and motor speed. Performance time is measured, with lower times indicative of higher executive function.
  • Cognitive Function as determined by PedsQL - (Child 8-12/Teen 13-18) [ Time Frame: up to 1 day ]
    Participants will undergo a series of cognitive tests to evaluate intelligence, memory, speed function, executive function, and psychiatric quality of life. The results of these test will be scored and reported individually. The Pediatric Quality of Life Inventory (PedsQL) is a 23-item survey assessing 4 functional dimensions: Physical, Emotional, Social, and School. Each item is scored on a 5-point Likert scale where 0 is 'not at all' and 4 is 'almost always'. Items are reversed scored (0=100, 1=75, 2=50, 3=25, 4=0) and linearly transformed to a 1-100 scale, where the higher the score, the better the Quality of Life.
  • Cerebral blood flow as determined by MRI [ Time Frame: up to 1 day ]
    CBF will be measured via MRI before OGTT (baseline) and after OGTT at 55 minutes.
  • Mediation analysis between insulin resistance, cerebral blood flow, and cognitive function [ Time Frame: through study completion (up to 2 years) ]
    Following relationships will be tested via linear regression:
    • insulin resistance and cerebral blood flow;
    • cerebral blood flow and cognitive tests; and
    • insulin resistance and cognitive tests with cerebral blood flow as the mediator
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04089332 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Insulin Resistance in Adolescents
Official Title  ICMJE Insulin Resistance, Cognitive Health, and Perfusion of the Adolescent Brain
Brief Summary The growing population of adolescents with insulin resistance (IR) is predicted to create a large public health burden in the next few decades. This study examines the function of brain blood vessels and cognitive function, to test if increasing severity of IR in adolescents is related to reduced cognitive function and reduced brain blood vessel function. Findings from this study may help create treatments to delay or prevent some of the negative effects of IR on cognitive and vascular health.
Detailed Description One in five American adolescents are obese, and many of these patients exhibit some level of insulin resistance (IR). IR is associated with cerebrovascular disease, reduced memory, attention, and cognition, but how IR contributes to these in the course of adolescent brain development is unclear. The goal of this proposal is to investigate the extent and by which IR drives reductions in neurocognitive function and cerebral blood flow (CBF) in adolescents at elevated risk for poor brain and cerebrovascular health. The overall goal of this research program is to investigate IR-related changes in neurocognitive and vascular function. The investigators propose to study adolescents across a spectrum of IR, from healthy to pre-diabetic, without confounding effects of age or diabetes— before the negative effects of IR can exert their full negative impact. The general hypothesis is that cognitive and vascular function is impaired via shift away from insulin-mediated vasodilation in brain blood vessels.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Insulin Resistance
Intervention  ICMJE
  • Other: Oral Glucose Tolerance Test
    Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
    Other Name: OGTT
  • Device: 3 Tesla MRI
    A 3 Tesla MRI will be used to assess brain structure, quantify cerebral blood flow and capture cerebral vessel structure at designated time points throughout the study visits.
    Other Name: MRI
  • Device: Intravenous Catheter
    A blood sampling IV catheter will be used to draw blood samples at specific time points throughout each study visit to measure concentrations of glucose and insulin.
    Other Name: Cath
  • Other: Cognitive Tests
    A battery of cognitive tests will be completed by the subject.
Study Arms  ICMJE Experimental: Enrolled, eligible
Single arm for eligible subjects
Interventions:
  • Other: Oral Glucose Tolerance Test
  • Device: 3 Tesla MRI
  • Device: Intravenous Catheter
  • Other: Cognitive Tests
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  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 12, 2019)
55
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 31, 2021
Estimated Primary Completion Date July 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 12-18 years inclusive
  • Typically developing and cognitively intact

Exclusion Criteria:

  • Diabetes (≥126 mg dL-1 fasting glucose)
  • Insulin treatment or sensitizing drugs
  • Diagnosis of kidney, pulmonary, or heart disease
  • Current smoking (defined as use of nicotine >5 times in the past month)
  • Pregnancy
  • Neurological or developmental disorders (e.g., intellectual disability, autism)
  • Significant head injury or medical conditions (e.g., concussion, encephalopathy, seizure disorder)
  • Inability to undergo the MRI procedure
  • Weight less than 94.5 lbs (42.9 kg) to adhere to safety guidelines regarding blood sampling and OGTT administration
  • Tanner Stage <3
  • Any other circumstance deemed by the PI not addressed above
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: William Schrage, PhD 6082627715 william.schrage@wisc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04089332
Other Study ID Numbers  ICMJE 2019-0361
1R21HD097510-01A1 ( U.S. NIH Grant/Contract )
A176000 ( Other Identifier: UW Madison )
EDUC/KINESIOLOGY/KINESIOLOG ( Other Identifier: UW Madison )
19PRE34450141 ( Other Grant/Funding Number: American Heart Association )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Wisconsin, Madison
Study Sponsor  ICMJE University of Wisconsin, Madison
Collaborators  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Principal Investigator: William Schrage, PhD University of Wisconsin, Madison
PRS Account University of Wisconsin, Madison
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP