Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04089332
Other study ID # 2019-0361
Secondary ID 1R21HD097510-01A
Status Completed
Phase N/A
First received
Last updated
Start date October 4, 2019
Est. completion date July 31, 2022

Study information

Verified date August 2022
Source University of Wisconsin, Madison
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

One in five American adolescents is obese. Up to half of those are already exhibiting insulin resistance (IR), a hallmark of metabolic syndrome and diabetes linked to serious life-altering health disorders, including cardiovascular and cerebrovascular disease. In adults, IR negatively affects brain structure and function and is reflected in lower regional brain volumes, perfusion, increased white matter hyperintensities and abnormal neuropsychological status, especially affecting memory and attention-all changes associated with accelerated cognitive and brain aging and increased risk of dementia. In an analogous fashion, a limited set of literature suggests adolescents with IR exhibit similar brain changes during maturation. The investigators hypothesize that the brains of obese adolescents are more susceptible to insults of IR during rapid brain development, positioning them on an abnormal cognitive trajectory, and predisposing them to issues related to learning, behavioral stress responses, and depression. While the metabolic consequences of IR are well described in adolescence, the impact of IR on their neurocognitive status (intelligence, memory, attention, executive function, processing speed) and cerebrovascular function and their interactions remains largely unexplored. This is important since in addition to its classic role as a metabolic hormone, insulin acts as a vasodilator and supports neurotrophic signaling in healthy humans. Therefore, dysfunctional insulin signaling may hold tremendous influence over brain health in adolescents during this vital period of brain development. New insight is required to understand where, when, and how IR negatively transforms brain health, including whether a dose-response exists between IR severity and anomalies in brain and cognition. The long-term goal of this research program is to determine the influence of IR on brain development in adolescents through the relationships between neurocognition and cerebral blood supply. The primary goal of the current project is to quantify fundamental neurocognitive and cerebrovascular function in relation to the severity of IR. The central hypothesis is that as IR worsens: a) subtle but meaningful neurocognitive declines emerge; b) regional brain perfusion is reduced primarily in areas linked to learning and memory despite preserved resting global cerebral blood flow (CBF); c) acute insulin surges exacerbate regional hypoperfusion, and d) cognitive scores will be lower, mediated in part by insulin-stimulated hypoperfusion. Participants will be recruited primarily from pediatric and pediatric endocrinology clinics via our collaborator, Dr. Aaron Carrel, and his staff in UWHC Pediatric Endocrinology. Additionally, participants will be recruited from the greater Madison, WI community.


Recruitment information / eligibility

Status Completed
Enrollment 18
Est. completion date July 31, 2022
Est. primary completion date July 31, 2022
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 12 Years to 18 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Other:
Oral Glucose Tolerance Test
Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
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.
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:
Cognitive Tests
A battery of cognitive tests will be completed by the subject.

Locations

Country Name City State
United States University of Wisconsin-Madison Madison Wisconsin

Sponsors (2)

Lead Sponsor Collaborator
University of Wisconsin, Madison Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Cognitive Function as determined by WASI (Verbal IQ) 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.
up to 1 day
Primary Cognitive Function as determined by WASI (Performance IQ) 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.
up to 1 day
Primary Cognitive Function as determined by NIH Toolbox (List Learning) Test 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.
up to 1 day
Primary Cognitive Function as determined by NIH Toolbox (Oral Symbol Digit Test) 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.
up to 1 day
Primary Cognitive Function as determined by NIH Toolbox (Flanker Inhibitory Control and Attention) 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.
up to 1 day
Primary Cognitive Function as determined by NIH Toolbox (Pattern Completion) 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.
up to 1 day
Primary Cognitive Function as determined by NIH Toolbox (Picture Sequence) 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.
up to 1 day
Primary Cognitive Function as determined by WRAML (Picture Memory) 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.
up to 1 day
Primary Cognitive Function as determined by D-KEFS (Color-Word Interference) 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.
up to 1 day
Primary Cognitive Function as determined by D-KEFS (Trail Making Test) 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.
up to 1 day
Primary Cognitive Function as determined by PedsQL - (Child 8-12/Teen 13-18) 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.
up to 1 day
Primary Cerebral blood flow as determined by MRI CBF will be measured via MRI before OGTT (baseline) and after OGTT at 55 minutes. up to 1 day
Primary Mediation analysis between insulin resistance, cerebral blood flow, and cognitive function 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
through study completion (up to 2 years)
See also
  Status Clinical Trial Phase
Completed NCT03142633 - MicroRNA as Biomarkers for Development of Metabolic Syndrome in Women With Polycystic Ovary Syndrome
Recruiting NCT04984226 - Sodium Bicarbonate and Mitochondrial Energetics in Persons With CKD Phase 2
Recruiting NCT05354245 - Using a Complex Carbohydrate Mixture to Steer Fermentation and Improve Metabolism in Adults With Overweight and Prediabetes (DISTAL) N/A
Completed NCT03383822 - Regulation of Endogenous Glucose Production by Brain Insulin Action in Insulin Resistance Phase 1/Phase 2
Recruiting NCT06007404 - Understanding Metabolism and Inflammation Risks for Diabetes in Adolescents
Suspended NCT03652987 - Endocrine and Menstrual Disturbances in Women With Polycystic Ovary Syndrome (PCOS)
Completed NCT04203238 - Potato Research for Enhancing Metabolic Outcomes N/A
Recruiting NCT03658564 - Preoperative Oral Carbohydrate Treatment Minimizes Insulin Resistance N/A
Completed NCT04183257 - Effect of Escalating Oral Vitamin D Replacement on HOMA-IR in Vitamin D Deficient Type 2 Diabetics Phase 4
Completed NCT04117802 - Effects of Maple Syrup on Gut Microbiota Diversity and Metabolic Syndrome N/A
Completed NCT03627104 - Effect of Dietary Protein and Energy Restriction in the Improvement of Insulin Resistance in Subjects With Obesity N/A
Completed NCT05124847 - TREating Pediatric Obesity N/A
Active, not recruiting NCT03288025 - Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE) N/A
Completed NCT03809182 - Effect of Dexmedetomidine on Postoperative Glucose and Insulin Levels. Phase 4
Completed NCT01809288 - Identifying Risk for Diabetes and Heart Disease in Women
Completed NCT04642482 - Synbiotic Therapy on Intestinal Microbiota and Insulin Resistance in Obesity Phase 4
Terminated NCT03278236 - Does Time Restricted Feeding Improve Glycaemic Control in Overweight Men? N/A
Not yet recruiting NCT06159543 - The Effects of Fresh Mango Consumption on Cardiometabolic Outcomes in Free-living Individuals With Prediabetes N/A
Withdrawn NCT04741204 - Metformin Use to Reduce Disparities in Newly Diagnosed Breast Cancer Phase 4
Not yet recruiting NCT05540249 - Pre-operative Carbohydrates in Diabetic Patients Undergoing CABG N/A