Type 2 Diabetes MellitusNCT03461510
Type 2 Diabetes and the Brain in Adolescents
A study testing Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp in people with Type 2 Diabetes Mellitus and Obesity, run by Nemours Children's Clinic at 1 site in United States.
Trial summary
This study evaluates differences in brain function and cognitive performance in adolescents with type 2 diabetes (T2D) compared to non diabetic controls (both obese and lean) and correlates these changes with obesity, insulin resistance, and glycemic control in youth with T2D. Read more about this study
- Who is it for?
- Ages 12 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus, Obesity, Pediatric Obesity
- What is being tested?
- Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Dec 2017to 30 Jan 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Type 2 Diabetes:
- BMI ≥85th percentile
- A1c ≥ 8%
- Pubertal
- Healthy Controls:
- BMI ≥85th percentile for Obese Controls
Show all 9Show fewer
- BMI < 85th percentile for Lean Controls
- Pubertal
- Normal A1c \& Fasting glucose
Who cannot join
- Significant developmental delay or learning disability
- Significant visual or auditory deficits
- Born <34 weeks gestation
- Neurologic disease
- Psychiatric disease requiring inpatient treatment
- Significant head trauma
Show all 10Show fewer
- Malignancy
- Pregnancy
- Weight > 350lb (MRI weight limit)
- Metal in the body (including dental braces)
Trial locations and contacts
1 site in 1 country.
United States1 site
Nemours Children's Health System
Jacksonville, Florida, 32207
About this study
Official title: Dysglycemia & Obesity: Impact on the Brain in Adolescents With Type 2 Diabetes
This study evaluates differences in brain function and cognitive performance in adolescents with type 2 diabetes (T2D) compared to non diabetic controls (both obese and lean) and correlates these changes with obesity, insulin resistance, and glycemic control in youth with T2D.
Read the detailed description
This is a cross-sectional study examining neurocognitive function and brain activity in resting state and during working memory and executive function tasks using blood oxygen level dependent (BOLD) functional MRI (fMRI) during hyperinsulinemic euglycemic and hyperglycemic clamps in obese adolescents with T2D compared to non-diabetic obese and lean controls. The investigators will measure glycemic control (acute hyperglycemia during clamps and glycemic variability) and insulin resistance to examine their association with neurocognitive metrics and brain functional activity.
There will be one screening visit and three study visits for subjects with T2D. One visit will consist of neurocognitive testing and dual energy X-ray absorptiometry (DEXA) of the whole body to assess body composition including fat mass. In the other two visits, subjects with T2D will undergo normal and high glucose clamps during fMRI.
Obese and lean control subjects will have one screening visit and two study visits, one for neurocognitive testing and DEXA and another for fMRI without glucose clamps. All subjects will have a blood sample obtained at the screening visit.
Only adolescents with type 2 diabetes will wear a continuous glucose monitor (CGM) for 6 days prior to neuroimaging to determine glycemic variability. A1C will be assessed at baseline.
Parents of subjects will also have abbreviated IQ testing.
- Conditions
- Type 2 Diabetes Mellitus, Obesity, Pediatric Obesity, Insulin Resistance, Dysglycemia, Hyperglycemia
- Being tested
- Hyperglycemic clamp, Hyperinsulinemic Euglycemic clamp
- Keywords
- Cognition, MRI, Functional MRI, Pediatric Obesity, Type 2 Diabetes Mellitus, Adolescents, Continuous Glucose Monitoring, Insulin Clamp
- Medical subject headings
- Diabetes Mellitus, Type 2, Obesity, Pediatric Obesity, Insulin Resistance, Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperglycemic clampProcedure or surgery
Subjects with T2D will receive IV Dextrose infusion to maintain plasma glucose at ~250 mg/dL during fMRI.
Hyperinsulinemic Euglycemic clampProcedure or surgery
Subjects with T2D will receive IV Dextrose and Insulin infusion to maintain plasma glucose at approximately 90 mg/dL during fMRI.
| Study group | Role | What they receive |
|---|---|---|
| Type 2 Diabetes | Experimental | Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp Receives: Procedure: Hyperglycemic clamp; Procedure: Hyperinsulinemic Euglycemic clamp |
| Lean Control | No intervention | Controls do not undergo Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp |
| Obese Control | No intervention | Controls do not undergo Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain Activity using functional MRI (fMRI)
The investigators will examine functional connectivity of brain networks during cross sectional resting-state and task-related (working memory and response inhibition) BOLD-fMRI activation. fMRI activation in adolescents with T2D will be compared to age- and sex- matched, non-diabetic, healthy lean and obese controls.
Measured: Baseline
Neurocognitive battery metrics including IQ as well as executive function and visual-spatial memory
The investigators will evaluate cognitive performance by examining test scores from neurocognitive metrics which reflect global IQ, spatial recognition, episodic memory, executive function (includes response inhibition, working memory), academic achievement, and processing speed. Adolescents with T2D will be compared to controls to determine whether these differences are associated with glycemic control, obesity, and insulin resistance.
Measured: Baseline
fMRI performance in relation to dysglycemia
In adolescents with T2D, the investigators will examine BOLD-fMRI brain activation in relation to acute hyperglycemia during glucose clamping, chronic hyperglycemia, glycemic variability, and insulin resistance.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2018
- Study start5 Dec 2017
- Primary completion30 Jan 2019
- Study completion30 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nemours Children's Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lydia Snyder, Nemours Children's Clinic
- Investigators
- Lydia Snyder, MD, Principal investigator, Nemours Children's Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03461510
- Sponsor's protocol ID
- 17-35
- Status last verified
- Sep 2019
- First submitted
- 4 Jan 2018
- Last updated
- 9 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Mazaika PK, Weinzimer SA, Mauras N, Buckingham B, White NH, Tsalikian E, Hershey T, Cato A, Aye T, Fox L, Wilson DM, Tansey MJ, Tamborlane W, Peng D, Raman M, Marzelli M, Reiss AL; Diabetes Research in Children Network (DirecNet). Variations in Brain Volume and Growth in Young Children With Type 1 Diabetes. Diabetes. 2016 Feb;65(2):476-85. doi: 10.2337/db15-1242. Epub 2015 Oct 28.
PubMed 26512024Mauras N, Mazaika P, Buckingham B, Weinzimer S, White NH, Tsalikian E, Hershey T, Cato A, Cheng P, Kollman C, Beck RW, Ruedy K, Aye T, Fox L, Arbelaez AM, Wilson D, Tansey M, Tamborlane W, Peng D, Marzelli M, Winer KK, Reiss AL; Diabetes Research in Children Network (DirecNet). Longitudinal assessment of neuroanatomical and cognitive differences in young children with type 1 diabetes: association with hyperglycemia. Diabetes. 2015 May;64(5):1770-9. doi: 10.2337/db14-1445. Epub 2014 Dec 8.
PubMed 25488901Marzelli MJ, Mazaika PK, Barnea-Goraly N, Hershey T, Tsalikian E, Tamborlane W, Mauras N, White NH, Buckingham B, Beck RW, Ruedy KJ, Kollman C, Cheng P, Reiss AL; Diabetes Research in Children Network (DirecNet). Neuroanatomical correlates of dysglycemia in young children with type 1 diabetes. Diabetes. 2014 Jan;63(1):343-53. doi: 10.2337/db13-0179. Epub 2013 Oct 29.
PubMed 24170697Bruehl H, Sweat V, Tirsi A, Shah B, Convit A. Obese Adolescents with Type 2 Diabetes Mellitus Have Hippocampal and Frontal Lobe Volume Reductions. Neurosci Med. 2011 Mar 1;2(1):34-42. doi: 10.4236/nm.2011.21005.
PubMed 21691448Yau PL, Javier DC, Ryan CM, Tsui WH, Ardekani BA, Ten S, Convit A. Preliminary evidence for brain complications in obese adolescents with type 2 diabetes mellitus. Diabetologia. 2010 Nov;53(11):2298-306. doi: 10.1007/s00125-010-1857-y. Epub 2010 Jul 30.
PubMed 20668831Yau PL, Kang EH, Javier DC, Convit A. Preliminary evidence of cognitive and brain abnormalities in uncomplicated adolescent obesity. Obesity (Silver Spring). 2014 Aug;22(8):1865-71. doi: 10.1002/oby.20801. Epub 2014 May 28.
PubMed 24891029Cui Y, Jiao Y, Chen YC, Wang K, Gao B, Wen S, Ju S, Teng GJ. Altered spontaneous brain activity in type 2 diabetes: a resting-state functional MRI study. Diabetes. 2014 Feb;63(2):749-60. doi: 10.2337/db13-0519. Epub 2013 Dec 18.
PubMed 24353185Marder TJ, Flores VL, Bolo NR, Hoogenboom WS, Simonson DC, Jacobson AM, Foote SE, Shenton ME, Sperling RA, Musen G. Task-induced brain activity patterns in type 2 diabetes: a potential biomarker for cognitive decline. Diabetes. 2014 Sep;63(9):3112-9. doi: 10.2337/db13-1783. Epub 2014 Apr 4.
PubMed 24705405
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dysglycemia & Obesity: Impact on the Brain in Adolescents With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT03461510
- Acronym / sponsor ID
- 17-35
- Conditions
- Type 2 Diabetes Mellitus, Obesity, Pediatric Obesity, Insulin Resistance, Dysglycemia, Hyperglycemia
- Keywords
- Cognition, MRI, Functional MRI, Pediatric Obesity, Type 2 Diabetes Mellitus, Adolescents, Continuous Glucose Monitoring, Insulin Clamp
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Nemours Children's ClinicUniversity, hospital or other
- Study start
- 5 Dec 2017 (actual)
- Primary completion
- 30 Jan 2019 (actual)
- Study completion
- 30 Jan 2019 (actual)
- First posted
- 12 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates differences in brain function and cognitive performance in adolescents with type 2 diabetes (T2D) compared to non diabetic controls (both obese and lean) and correlates these changes with obesity, insulin resistance, and glycemic control in youth with T2D.
Detailed description
This is a cross-sectional study examining neurocognitive function and brain activity in resting state and during working memory and executive function tasks using blood oxygen level dependent (BOLD) functional MRI (fMRI) during hyperinsulinemic euglycemic and hyperglycemic clamps in obese adolescents with T2D compared to non-diabetic obese and lean controls. The investigators will measure glycemic control (acute hyperglycemia during clamps and glycemic variability) and insulin resistance to examine their association with neurocognitive metrics and brain functional activity.
There will be one screening visit and three study visits for subjects with T2D. One visit will consist of neurocognitive testing and dual energy X-ray absorptiometry (DEXA) of the whole body to assess body composition including fat mass. In the other two visits, subjects with T2D will undergo normal and high glucose clamps during fMRI.
Obese and lean control subjects will have one screening visit and two study visits, one for neurocognitive testing and DEXA and another for fMRI without glucose clamps. All subjects will have a blood sample obtained at the screening visit.
Only adolescents with type 2 diabetes will wear a continuous glucose monitor (CGM) for 6 days prior to neuroimaging to determine glycemic variability. A1C will be assessed at baseline.
Parents of subjects will also have abbreviated IQ testing.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Type 2 Diabetes | Experimental | Procedure: Hyperglycemic clamp, Procedure: Hyperinsulinemic Euglycemic clampHyperglycemic clamp and Hyperinsulinemic Euglycemic clamp |
| Lean Control | No intervention | –Controls do not undergo Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp |
| Obese Control | No intervention | –Controls do not undergo Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp |
Who may qualify
- Ages
- 12 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- BMI ≥85th percentile
- A1c ≥ 8%
- Pubertal
- BMI ≥85th percentile for Obese Controls
- BMI < 85th percentile for Lean Controls
Key exclusion criteria (10 listed)
- Significant developmental delay or learning disability
- Significant visual or auditory deficits
- Born <34 weeks gestation
- Neurologic disease
- Psychiatric disease requiring inpatient treatment
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 |
|---|---|---|
| Hyperglycemic clampSubjects with T2D will receive IV Dextrose infusion to maintain plasma glucose at ~250 mg/dL during fMRI. | Procedure or surgery | Type 2 Diabetes |
| Hyperinsulinemic Euglycemic clampSubjects with T2D will receive IV Dextrose and Insulin infusion to maintain plasma glucose at approximately 90 mg/dL during fMRI. | Procedure or surgery | Type 2 Diabetes |
Primary outcome
Brain Activity using functional MRI (fMRI)
Time frame: Baseline
The investigators will examine functional connectivity of brain networks during cross sectional resting-state and task-related (working memory and response inhibition) BOLD-fMRI activation. fMRI activation in adolescents with T2D will be compared to age- and sex- matched, non-diabetic, healthy lean and obese controls.
Neurocognitive battery metrics including IQ as well as executive function and visual-spatial memory
Time frame: Baseline
The investigators will evaluate cognitive performance by examining test scores from neurocognitive metrics which reflect global IQ, spatial recognition, episodic memory, executive function (includes response inhibition, working memory), academic achievement, and processing speed. Adolescents with T2D will be compared to controls to determine whether these differences are associated with glycemic control, obesity, and insulin resistance.
fMRI performance in relation to dysglycemia
Time frame: Baseline
In adolescents with T2D, the investigators will examine BOLD-fMRI brain activation in relation to acute hyperglycemia during glucose clamping, chronic hyperglycemia, glycemic variability, and insulin resistance.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2019.
- Background: PubMed 26512024Mazaika PK, Weinzimer SA, Mauras N, Buckingham B, White NH, Tsalikian E, Hershey T, Cato A, Aye T, Fox L, Wilson DM, Tansey MJ, Tamborlane W, Peng D, Raman M, Marzelli M, Reiss AL; Diabetes Research in Children Network (DirecNet). Variations in Brain Volume and Growth in Young Children With Type 1 Diabetes. Diabetes. 2016 Feb;65(2):476-85. doi: 10.2337/db15-1242. Epub 2015 Oct 28.
- Background: PubMed 25488901Mauras N, Mazaika P, Buckingham B, Weinzimer S, White NH, Tsalikian E, Hershey T, Cato A, Cheng P, Kollman C, Beck RW, Ruedy K, Aye T, Fox L, Arbelaez AM, Wilson D, Tansey M, Tamborlane W, Peng D, Marzelli M, Winer KK, Reiss AL; Diabetes Research in Children Network (DirecNet). Longitudinal assessment of neuroanatomical and cognitive differences in young children with type 1 diabetes: association with hyperglycemia. Diabetes. 2015 May;64(5):1770-9. doi: 10.2337/db14-1445. Epub 2014 Dec 8.
- Background: PubMed 24170697Marzelli MJ, Mazaika PK, Barnea-Goraly N, Hershey T, Tsalikian E, Tamborlane W, Mauras N, White NH, Buckingham B, Beck RW, Ruedy KJ, Kollman C, Cheng P, Reiss AL; Diabetes Research in Children Network (DirecNet). Neuroanatomical correlates of dysglycemia in young children with type 1 diabetes. Diabetes. 2014 Jan;63(1):343-53. doi: 10.2337/db13-0179. Epub 2013 Oct 29.
- Background: PubMed 21691448Bruehl H, Sweat V, Tirsi A, Shah B, Convit A. Obese Adolescents with Type 2 Diabetes Mellitus Have Hippocampal and Frontal Lobe Volume Reductions. Neurosci Med. 2011 Mar 1;2(1):34-42. doi: 10.4236/nm.2011.21005.
- Background: PubMed 20668831Yau PL, Javier DC, Ryan CM, Tsui WH, Ardekani BA, Ten S, Convit A. Preliminary evidence for brain complications in obese adolescents with type 2 diabetes mellitus. Diabetologia. 2010 Nov;53(11):2298-306. doi: 10.1007/s00125-010-1857-y. Epub 2010 Jul 30.
- Background: PubMed 24891029Yau PL, Kang EH, Javier DC, Convit A. Preliminary evidence of cognitive and brain abnormalities in uncomplicated adolescent obesity. Obesity (Silver Spring). 2014 Aug;22(8):1865-71. doi: 10.1002/oby.20801. Epub 2014 May 28.
- Background: PubMed 24353185Cui Y, Jiao Y, Chen YC, Wang K, Gao B, Wen S, Ju S, Teng GJ. Altered spontaneous brain activity in type 2 diabetes: a resting-state functional MRI study. Diabetes. 2014 Feb;63(2):749-60. doi: 10.2337/db13-0519. Epub 2013 Dec 18.
- Background: PubMed 24705405Marder TJ, Flores VL, Bolo NR, Hoogenboom WS, Simonson DC, Jacobson AM, Foote SE, Shenton ME, Sperling RA, Musen G. Task-induced brain activity patterns in type 2 diabetes: a potential biomarker for cognitive decline. Diabetes. 2014 Sep;63(9):3112-9. doi: 10.2337/db13-1783. Epub 2014 Apr 4.
- Individual participant dataSharing planned: Undecided
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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.
Lydia Snyder, MD principal investigator
Nemours Children's Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hyperglycemic clamp and Hyperinsulinemic Euglycemic clamp in people with Type 2 Diabetes Mellitus and Obesity, run by Nemours Children's Clinic 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 9 inclusion and 10 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 9 Sep 2019. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Brain Activity using functional MRI (fMRI) (time frame: Baseline). The study lists 3 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 NCT03461510, which also lists 8 linked publications.
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 9 Sep 2019.