Insulin Resistance in Adolescents

NCT04089332 | Completed Results DMC

• 6 other identifiers: 2019-03611R21HD097510-01A1A176000EDUC/KINESIOLOGY/KINESIOLOG19PRE34450141Protocol Version 9/24/2021
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Insulin Resistance

Outcome Measures

Primary Outcomes (4)

• Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)

  HOMA-IR was measured from each participant at baseline (up to 1 hour visit) and a battery of cognitive instruments (listed here) were measured at a different study visit (2-3 hours of time). A relationship between individual HOMA-IR and Cognitive Function was hypothesized and a measured via Linear Regression (R-squared).

  data collected at baseline visit (HOMA-IR) and one other study visit (Cognitive Function Tests) (up to 4 hours total time of data collection over two visits - data collection not temporally dependent)

• Change in Cerebral Blood Flow (CBF) as Determined by MRI (mL/100g/Min)

  CBF will be measured via MRI before OGTT (baseline) and after OGTT at Peak insulin.

  1 study visit, measured at baseline and peak insulin (45-60 minutes after baseline)

• Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)

  Cerebral Blood Flow was measured from each participant at baseline (without OGTT MRI Visit) and a battery of cognitive instruments (those listed below) were measured at a different study visit. A relationship between individual Cerebral Blood Flow and Cognitive Function was hypothesized and a measured via Linear Regression (R-squared).

  data collected at baseline (CBF - up to 1 hour) and Cognitive Function data collected at another study visit (up to 3 hours), data collection over 2 study visits up to 4 hours total, data collection not temporally dependent

• Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function

  Mediation analysis is a statistical method used to explain the influence of an outside variable (mediator) that may modify the direct relationship between the Independent (X) and Dependent variable (Y). (X - Mediator - Y) Mediation analysis was used to explore the impact of cerebral blood flow on the relationship between HOMA-IR and cognitive function. This analysis was conducted on 11 separate cognitive function tests, looking at verbal skills, memory, executive function, and self-reported quality of life rating. In the first set of analyses, the mediator was "grey matter baseline", which is the cerebral blood flow in the resting state. The second set of analyses, the mediator was "grey matter change with OGTT", which is the cerebral blood flow changing from rest to response from Oral Glucose Tolerance Test (OGTT). Positive/negative effect numbers indicated that the total effect of the relationship was positive/negative.

  through study completion (up to 2 years)

Study Arms (1)

Enrolled, eligible

EXPERIMENTAL

Single arm for eligible subjects

Other: Oral Glucose Tolerance Test (OGTT); Device: 3 Tesla MRI; Device: Intravenous Catheter; Other: Cognitive Tests

Interventions

Oral Glucose Tolerance Test (OGTT) OTHER

Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.

Also known as: OGTT

Enrolled, eligible

3 Tesla MRI DEVICE

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.

Also known as: MRI

Enrolled, eligible

Intravenous Catheter DEVICE

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.

Also known as: Cath

Enrolled, eligible

Cognitive Tests OTHER

A battery of cognitive tests will be completed by the subject.

Enrolled, eligible

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Wisconsin-Madison

Madison, Wisconsin, 53706, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Glucose Tolerance Test; Vascular Access Devices; Neuropsychological Tests

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques; Catheters; Equipment and Supplies; Psychological Tests; Behavioral Disciplines and Activities

Limitations and Caveats

Study conduct was impacted by the COVID-19 pandemic. Safety issues with the target population during this time influenced whether participants completed any or all of the study visits. Due to the small sample size, the statistic tests are likely underpowered and should be interpreted with caution.

Results Point of Contact

• Title: Dr. William Schrage
• Organization: University of Wisconsin - Madison

william.schrage@wisc.edu

608-262-7715

Study Officials

• William Schrage, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2019
• First Posted: September 13, 2019
• Study Start: October 4, 2019
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2022
• Last Updated: September 5, 2024
• Results First Posted: September 5, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)