Insulin ResistanceNCT04089332

Insulin Resistance in Adolescents

A study testing Oral Glucose Tolerance Test (OGTT), 3 Tesla MRI and Intravenous Catheter in people with Insulin Resistance, run by University of Wisconsin, Madison at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 12 to 18 yearsHealthy volunteers can take part
Conditions the study is for: Insulin Resistance
What is being tested?: Oral Glucose Tolerance Test (OGTT), 3 Tesla MRI and Intravenous Catheter
Type of treatment: Pill or oral medicine, Injection or infusion, Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 23 participants
Where: 1 siteUnited States
Study dates: 4 Oct 2019to 31 Jul 2022
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 to 18 years
All sexes
Healthy volunteers accepted
Child, Adult

Who may be able to join

Age 12-18 years inclusive
Typically developing and cognitively intact

Who cannot join

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)

Show all 11Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Wisconsin-Madison
Madison, Wisconsin, 53706

Other trials in United States

About this study

Official title: Insulin Resistance, Cognitive Health, and Perfusion of the Adolescent Brain

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.

Read the detailed 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.

Conditions: Insulin Resistance
Being tested: Oral Glucose Tolerance Test (OGTT), 3 Tesla MRI, Intravenous Catheter, Cognitive Tests
Medical subject headings: Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Oral Glucose Tolerance Test (OGTT)Other
Also called OGTT
Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
3 Tesla MRIDevice
Also called 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 CatheterDevice
Also called Cath
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.
Cognitive TestsOther
A battery of cognitive tests will be completed by the subject.

Study groups in NCT04089332
Study group	Role	What they receive
Enrolled, eligible	Experimental	Single arm for eligible subjects Receives: Other: Oral Glucose Tolerance Test (OGTT); Device: 3 Tesla MRI; Device: Intravenous Catheter; Other: Cognitive Tests

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: through study completion (up to 2 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Oct 201931 Jul 2022

First posted13 Sep 2019
Study start4 Oct 2019
Primary completion31 Jul 2022
Study completion31 Jul 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Insulin ResistanceStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04089332
Sponsor's protocol ID: 2019-0361
Other IDs: 1R21HD097510-01A1, A176000, EDUC/KINESIOLOGY/KINESIOLOG, 19PRE34450141, Protocol Version 9/24/2021
Status last verified: Aug 2024
First submitted: 3 Sep 2019
Last updated: 5 Sep 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Insulin Resistance trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Insulin Resistance, Cognitive Health, and Perfusion of the Adolescent Brain
ClinicalTrials.gov ID: NCT04089332
Acronym / sponsor ID: 2019-0361
Conditions: Insulin Resistance
Study type: Interventional
Recruitment status: Completed
Enrolment: 23 participants (actual)
Lead sponsor: University of Wisconsin, MadisonUniversity, hospital or other
Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study start: 4 Oct 2019 (actual)
Primary completion: 31 Jul 2022 (actual)
Study completion: 31 Jul 2022 (actual)
First posted: 13 Sep 2019 (actual)
Results: Posted 5 Sep 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Enrolled, eligible	Experimental	Other: Oral Glucose Tolerance Test (OGTT), Device: 3 Tesla MRI, Device: Intravenous Catheter, Other: Cognitive TestsSingle arm for eligible subjects

Who may qualify

Ages: 12 to 18 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (2 listed)

Age 12-18 years inclusive
Typically developing and cognitively intact

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Oral Glucose Tolerance Test (OGTT)Also: OGTTEligible subjects will undergo MRI scanning before and after oral glucose tolerance test.	Other	Enrolled, eligible
3 Tesla MRIAlso: MRIA 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.	Device	Enrolled, eligible
Intravenous CatheterAlso: CathA 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.	Device	Enrolled, eligible
Cognitive TestsA battery of cognitive tests will be completed by the subject.	Other	Enrolled, eligible

Primary outcome

Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
Time frame: 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)
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).
Change in Cerebral Blood Flow (CBF) as Determined by MRI (mL/100g/Min)
Time frame: 1 study visit, measured at baseline and peak insulin (45-60 minutes after baseline)
CBF will be measured via MRI before OGTT (baseline) and after OGTT at Peak insulin.
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
Time frame: 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
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).
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
Time frame: through study completion (up to 2 years)
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.

Results and safety

Results posted to the registry on 5 Sep 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Enrolled, Eligible	23	15

Primary outcome: Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)

Time frame: 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). Number. Unit: R-squared

Measure	Enrolled, Eligible n = 13
WASI II (Verbal IQ) Measure of intellectual ability, sub-tests Vocabulary and Similarities	0.205
WASI II (Performance IQ) Measure of intellectual ability, sub-tests Block Design, Matrix Reasoning	0.299
NIH Toolbox (List Learning) A cognitive measure of working memory	0.738
NIH Toolbox (Oral Symbol Digit Test) A cognitive measure of processing speed (numbers/symbols)	0.0264
NIH Toolbox (Flanker Inhibitory Control and Attention) Executive function measure	0.186
NIH Toolbox (Pattern Comparison) A cognitive measure of processing speed (stimuli)	0.04
NIH Toolbox (Picture Sequence) A cognitive measure of episodic memory	0.47
WRAML (Picture Memory) A general memory measure of picture recognition	0.0572

Enrolled, Eligible: Slope: -0.4465, p = 0.162, Regression, Linear
Enrolled, Eligible: Slope: 0.6704, p = 0.082, Regression, Linear
Enrolled, Eligible: Slope: -0.8486, p = 0.286, Regression, Linear

Population analysed: This includes all the participants that completed the cognitive visit of the study. Because data collected in each visit was not dependent on other visits in a temporal manner, study visits occurred in any order.

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

Time frame: 1 study visit, measured at baseline and peak insulin (45-60 minutes after baseline). Mean (Standard Deviation). Unit: mL/100g/min

Measure	Enrolled, Eligible n = 11
Perfusion of Gray Matter at Baseline	64.25666 (11.24309)
Perfusion of Gray Matter at Peak Insulin (Avg. 45 min)	66.96387836 (13.93884706)
Change in Perfusion of Gray Matter	2.707215114 (5.642163965)

Enrolled, Eligible: Slope: -1.1138, p = 0.558, Regression, Linear
Enrolled, Eligible: Slope: -5.8089, p = 0.057, Regression, Linear

Primary outcome: Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)

Time frame: 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. Number. Unit: R-squared

Measure	Enrolled, Eligible n = 13
WASI II (Verbal IQ) Measure of intellectual ability, sub-tests Vocabulary and Similarities.	0.132
WASI II (Performance IQ) Measure of intellectual ability, sub-tests Block Design, Matrix Reasoning	0.119
NIH Toolbox (List Learning) A cognitive measure of working memory	0.06
NIH Toolbox (Oral Symbol Digit Test) A cognitive measure of processing speed (numbers/symbols)	0.0593
NIH Toolbox (Flanker Inhibitory Control and Attention) Executive function measure	0.366
NIH Toolbox (Pattern Comparison) A cognitive measure of processing speed (stimuli)	0.000497
NIH Toolbox (Picture Sequence) A cognitive measure of episodic memory	0.0688
WRAML (Picture Memory) A general memory measure of picture recognition	0.185

Enrolled, Eligible: Slope: -0.4465, p = 0.377, Regression, Linear
Enrolled, Eligible: Slope: 0.6704, p = 0.402, Regression, Linear
Enrolled, Eligible: Slope: -0.8486, p = 0.203, Regression, Linear

Primary outcome: Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function

Time frame: through study completion (up to 2 years). Number. Unit: beta value

Measure	Enrolled, Eligible n = 13
HOMA-IR vs WASii- Verbal (Grey Matter Baseline)	1.6787
HOMA-IR vs WASii-Performance (grey Matter Baseline)	-3.3431
HOMA-IR vs WRAML (Grey Matter Baseline)	-0.8194
HOMA-IR vs DKEFS Trail Making (Grey Matter Baseline)	-0.1702
HOMA-IR vs DKEFS Inhibition Stroop (Grey Matter Baseline)	-0.2095
HOMA-IR vs PEDS QL Child Report (Grey Matter Baseline)	30.7925
HOMA-IR vs NIH Toolbox Verbal List Learning (Grey Matter Baseline)	0.5834
HOMA-IR vs NIH Toolbox Oral Digit Symbol (Grey Matter Baseline)	6.98

Population analysed: Mediation analysis was conducted on a limited data set due to the low number of participants.

Adverse events

Time frame: up to 1 year and 9 months (this was the longest any one participant was on study). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Enrolled, Eligible	0 of 23 (0%)	2 of 23 (8.7%)	0 of 23

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

William Schrage, PhD principal investigator

University of Wisconsin, Madison

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Oral Glucose Tolerance Test (OGTT), 3 Tesla MRI and Intravenous Catheter in people with Insulin Resistance, run by University of Wisconsin, Madison at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) (time frame: 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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04089332.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2024.