Trial Outcomes & Findings for Insulin Resistance in Adolescents (NCT NCT04089332)
NCT ID: NCT04089332
Last Updated: 2024-09-05
Results Overview
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).
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
23 participants
Primary outcome timeframe
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)
Results posted on
2024-09-05
Participant Flow
Participants were enrolled from October 2019 to April 2022. Participants were 12-18 years old during Covid-19 pandemic, and thus had very delayed access to vaccines, limiting enrollment. Pandemic related safety issues effected study conduct. Not all enrolled participants completed all (up to 5, 3 for the primary aims) study visits as a result. Because the data collected in each visit was not dependent on the other visit in a temporal manner, the study visits could occur in any order.
34 participants were consented, but due to the Covid-19 pandemic, only 23 participants started the study (completed at least 1 study visit).
Participant milestones
| Measure |
Enrolled, Eligible
Oral Glucose Tolerance Test: Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
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.
Cognitive Tests: A battery of cognitive tests will be completed by the subject.
|
|---|---|
|
Overall Study
STARTED
|
23
|
|
Overall Study
Completed Cognitive Tests
|
13
|
|
Overall Study
Completed OGTT
|
17
|
|
Overall Study
Completed MRI Structural Visit
|
16
|
|
Overall Study
Completed With Data to Analyze
|
15
|
|
Overall Study
Participants With Data for Change in CBF
|
11
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
8
|
Reasons for withdrawal
| Measure |
Enrolled, Eligible
Oral Glucose Tolerance Test: Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
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.
Cognitive Tests: A battery of cognitive tests will be completed by the subject.
|
|---|---|
|
Overall Study
COVID-19 Pandemic safety issues
|
6
|
|
Overall Study
Moved in the MRI, no analysis possible
|
1
|
|
Overall Study
Completed only OGTT, no analysis possible
|
1
|
Baseline Characteristics
Insulin Resistance in Adolescents
Baseline characteristics by cohort
| Measure |
Enrolled, Eligible
n=15 Participants
Oral Glucose Tolerance Test: Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
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.
Cognitive Tests: A battery of cognitive tests will be completed by the subject.
|
|---|---|
|
Age, Continuous
|
14.53 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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)Population: 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.
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).
Outcome measures
| Measure |
Enrolled, Eligible
n=13 Participants
Oral Glucose Tolerance Test (OGTT): Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
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.
Cognitive Tests: A battery of cognitive tests will be completed by the subject.
|
|---|---|
|
Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
WASI II (Verbal IQ) Measure of intellectual ability, sub-tests Vocabulary and Similarities
|
0.205 R-squared
|
|
Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
WASI II (Performance IQ) Measure of intellectual ability, sub-tests Block Design, Matrix Reasoning
|
0.299 R-squared
|
|
Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
NIH Toolbox (List Learning) A cognitive measure of working memory
|
0.738 R-squared
|
|
Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
NIH Toolbox (Oral Symbol Digit Test) A cognitive measure of processing speed (numbers/symbols)
|
0.0264 R-squared
|
|
Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
NIH Toolbox (Flanker Inhibitory Control and Attention) Executive function measure
|
0.186 R-squared
|
|
Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
NIH Toolbox (Pattern Comparison) A cognitive measure of processing speed (stimuli)
|
0.04 R-squared
|
|
Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
NIH Toolbox (Picture Sequence) A cognitive measure of episodic memory
|
0.47 R-squared
|
|
Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
WRAML (Picture Memory) A general memory measure of picture recognition
|
0.0572 R-squared
|
|
Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
D-KEFS (Color Word Interference) A measure of cognitive flexibility through inhibition
|
0.000224 R-squared
|
|
Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
D-KEFS (Trail Making Test) A measure of mental flexibility (motor speed)
|
0.392 R-squared
|
|
Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
Peds QL (Child 8-12 / Teen 13-18) A measure of health-related quality of life (HRQOL) in children
|
0.481 R-squared
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Enrolled, Eligible
n=11 Participants
Oral Glucose Tolerance Test (OGTT): Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
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.
Cognitive Tests: A battery of cognitive tests will be completed by the subject.
|
|---|---|
|
Change in Cerebral Blood Flow (CBF) as Determined by MRI (mL/100g/Min)
Perfusion of Gray Matter at Baseline
|
64.25666 mL/100g/min
Standard Deviation 11.24309
|
|
Change in Cerebral Blood Flow (CBF) as Determined by MRI (mL/100g/Min)
Perfusion of Gray Matter at Peak Insulin (Avg. 45 min)
|
66.96387836 mL/100g/min
Standard Deviation 13.93884706
|
|
Change in Cerebral Blood Flow (CBF) as Determined by MRI (mL/100g/Min)
Change in Perfusion of Gray Matter
|
2.707215114 mL/100g/min
Standard Deviation 5.642163965
|
PRIMARY outcome
Timeframe: 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 dependentPopulation: 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.
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).
Outcome measures
| Measure |
Enrolled, Eligible
n=13 Participants
Oral Glucose Tolerance Test (OGTT): Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
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.
Cognitive Tests: A battery of cognitive tests will be completed by the subject.
|
|---|---|
|
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
WASI II (Verbal IQ) Measure of intellectual ability, sub-tests Vocabulary and Similarities.
|
0.132 R-squared
|
|
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
WASI II (Performance IQ) Measure of intellectual ability, sub-tests Block Design, Matrix Reasoning
|
0.119 R-squared
|
|
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
NIH Toolbox (List Learning) A cognitive measure of working memory
|
0.06 R-squared
|
|
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
NIH Toolbox (Oral Symbol Digit Test) A cognitive measure of processing speed (numbers/symbols)
|
0.0593 R-squared
|
|
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
NIH Toolbox (Flanker Inhibitory Control and Attention) Executive function measure
|
0.366 R-squared
|
|
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
NIH Toolbox (Pattern Comparison) A cognitive measure of processing speed (stimuli)
|
0.000497 R-squared
|
|
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
NIH Toolbox (Picture Sequence) A cognitive measure of episodic memory
|
0.0688 R-squared
|
|
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
WRAML (Picture Memory) A general memory measure of picture recognition
|
0.185 R-squared
|
|
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
D-KEFS (Color-Word Interference) A measure of cognitive flexibility through inhibition
|
0.234 R-squared
|
|
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
D-KEFS (Trail Making Test) A measure of mental flexibility (motor speed)
|
0.00466 R-squared
|
|
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
PedsQL (Child 8-12 / Teen 13-18) A measure of health-related quality of life (HRQOL) in children
|
0.0344 R-squared
|
PRIMARY outcome
Timeframe: through study completion (up to 2 years)Population: Mediation analysis was conducted on a limited data set due to the low number of participants.
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.
Outcome measures
| Measure |
Enrolled, Eligible
n=13 Participants
Oral Glucose Tolerance Test (OGTT): Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
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.
Cognitive Tests: A battery of cognitive tests will be completed by the subject.
|
|---|---|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs WASii- Verbal (Grey Matter Baseline)
|
1.6787 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs WASii-Performance (grey Matter Baseline)
|
-3.3431 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs WRAML (Grey Matter Baseline)
|
-0.8194 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs DKEFS Trail Making (Grey Matter Baseline)
|
-0.1702 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs DKEFS Inhibition Stroop (Grey Matter Baseline)
|
-0.2095 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs PEDS QL Child Report (Grey Matter Baseline)
|
30.7925 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs NIH Toolbox Verbal List Learning (Grey Matter Baseline)
|
0.5834 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs NIH Toolbox Oral Digit Symbol (Grey Matter Baseline)
|
6.98 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs NIH Toolbox Flanker (Grey Matter Baseline)
|
1.0747 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs NIH Toolbox Pattern Comparison (Grey Matter Baseline)
|
2.3718 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs NIH Toolbox Picture Memory (Grey Matter Baseline)
|
-0.9954 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs WASii- Verbal (Grey Matter Change with OGTT)
|
-0.9125 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs WASii-Performance (grey Matter Change with OGTT)
|
-2.8222 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs WRAML (Grey Matter Change with OGTT)
|
-0.0008 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs DKEFS Trail Making (Grey Matter Change with OGTT)
|
0.1719 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs DKEFS Inhibition Stroop (Grey Matter Change with OGTT)
|
-0.3754 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs PEDS QL Child Report (Grey Matter Change with OGTT)
|
-7.4081 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs NIH Toolbox Verbal List Learning (Grey Matter Change with OGTT)
|
0.2067 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs NIH Toolbox Oral Digit Symbol (Grey Matter Change with OGTT)
|
-2.1898 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs NIH Toolbox Flanker (Grey Matter Change with OGTT)
|
-2.8883 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs NIH Toolbox Pattern Comparison (Grey Matter Change with OGTT)
|
0.5842 beta value
|
|
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
HOMA-IR vs NIH Toolbox Picture Memory (Grey Matter Change with OGTT)
|
-1.5724 beta value
|
Adverse Events
Enrolled, Eligible
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Enrolled, Eligible
n=23 participants at risk
Single arm for eligible subjects
Oral Glucose Tolerance Test: Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
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.
Cognitive Tests: A battery of cognitive tests will be completed by the subject.
|
|---|---|
|
General disorders
Unrelated Broken Bone
|
4.3%
1/23 • Number of events 1 • up to 1 year and 9 months (this was the longest any one participant was on study)
|
|
General disorders
Unrelated Hip Injury
|
4.3%
1/23 • Number of events 1 • up to 1 year and 9 months (this was the longest any one participant was on study)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place