IGT - Impaired Glucose ToleranceNCT03195400
Pathogenesis of Youth Onset Type 2 Diabetes and Prediabetes
An observational study of IGT - Impaired Glucose Tolerance and T2D, run by Yale University at 1 site in United States.
Trial summary
Type 2 Diabetes (T2D) in obese youth is often preceded by a prediabetic state called: Impaired Glucose Tolerance (IGT), which is associated with a pre-existing defect in insulin secretion. Read more about this study
- Who is it for?
- Ages 12 to 18 years
- Conditions the study is for
- IGT - Impaired Glucose Tolerance, T2D
- What is being tested?
- Oral Glucose Tolerance Test, Hyperglycemic Clamp and Isoglycemic Intravenous Glucose Test
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2017to 12 Aug 2022
- Phase
- Observational
- 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
- No healthy volunteers
- Child, Adult
Study population: Subjects will be selected from the Yale Pediatric Obesity Clinic or from the existing cohort of subjects who have had Oral Glucose Tolerance Tests and genotyping. Subjects will be Pre IGT and IGT adolescents 12-18 years old with either the CC or TT genotype. 50 CC pre IGT/IGT obese patients and 50 TT pre IGT/IGT obese patients will be rectruited.
Who may be able to join
- Good general health, taking no medication on a chronic basis;
- Age 12 to 18 yrs, in puberty (girls and boys: Tanner stage II - IV),
- BMI (BMI >85th%) indicating obesity,
- Girls who are menstruating must have a negative pregnancy test during the study and, when possible, be in the follicular phase during infusion study visits (The follicular phase will be identified according to the last menstrual period record and/or according to the oral contraceptive assumption schedule. The investigators will not perform ovulation testing or hormonal assays);
- Subject must have normal liver and kidney function, amylase and lipase levels.
- Pre-IGT or IGT
- TT or CC genotype.
Who cannot join
- Baseline creatinine >1.0 mg;
- Pregnancy;
- Presence of endocrinopathies (e.g. Cushing syndrome);
- Cardiac, renal or pulmonary or other chronic illness;
- Adolescents with psychiatric disorder or with substance abuse history and taking the drugs that affect glucose metabolism, such as any form of steroids, antipsychotics, progesterone preparations, and others.
Trial locations and contacts
1 site in 1 country.
About this study
Type 2 Diabetes (T2D) in obese youth is often preceded by a prediabetic state called: Impaired Glucose Tolerance (IGT), which is associated with a pre-existing defect in insulin secretion. This study intends to determine if genetic factors are associated with defects in insulin secretion, the incretin system and hepatic insulin resistance in obese adolescents. The long-term goal of this study is to generate information on both the genetics as well as the pathophysiology of Type 2 Diabetes in Youth, which ultimately might guide the investigators towards better preventive and treatment avenues.
Read the detailed description
The Specific Aims of this study are:
Aim 1a. To delineate the effects of TCF7L2 rs7903146 on functional Beta-Cell Capacity in obese adolescents with Impaired Glucose Tolerance (IGT) and pre-IGT.
Aim 1b. To determine if the risk genotype in TCF7L2 is associated with worsening in beta cell function longitudinally, thereby affecting changes in glucose tolerance.
Aim 2. To examine the functional effect of the rs7903146 variant in the TCF7L2 gene on a) incretin effect in obese adolescents with IGT and pre-IGT.
Aim 3. To determine the functional effects of TCF7L2 rs7903146 SNP on hepatic glucose fluxes in obese adolescents with IGT and pre-IGT.
- Conditions
- IGT - Impaired Glucose Tolerance, T2D
- Being tested
- Oral Glucose Tolerance Test, Hyperglycemic Clamp, Isoglycemic Intravenous Glucose Test, Hyperinsulinemic Euglycemic Clamp and 2H20
- Medical subject headings
- Glucose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Glucose Tolerance TestDiagnostic test
Also called OGTT
The oral glucose tolerance test (OGTT) measures the body's ability to use a type of sugar, called glucose, that is the body's main source of energy. An OGTT can be used to diagnose prediabetes and diabetes.
Hyperglycemic ClampDiagnostic test
Also called Infusion Study
Test of beta-cell function and insulin secretion. Involves increasing and maintaining blood glucose concentration with IV variable infusion of dextrose.
Isoglycemic Intravenous Glucose TestDiagnostic test
Also called IsoG IVGT
Test which exposes pancreas to blood glucose levels matched to the ones obtained at the OGTT.
Hyperinsulinemic Euglycemic Clamp and 2H20Diagnostic test
Also called E Clamp with labeled water
Test is used to assess insulin effects on hepatic glucose production.
| Study group | Role | What they receive |
|---|---|---|
| CC Genotype | Subjects who have not already been tested previously will be tested for the TCF7L2 genotype to determine if they are TT or CC. An anticipated 50 obese CC adolescents with IGT or pre-IGT with similar age, pubertal stage, ethnicity and Body Mass Index (BMI) will enrolled. Subjects will undergo Oral Glucose Tolerance Test, Hyperglycemic Clamp, Isoglycemic Intravenous Glucose Test IsoG IVGT and Hyperinsulinemic Euglycemic Clamp and 2H20. Receives: Diagnostic Test: Oral Glucose Tolerance Test; Diagnostic Test: Hyperglycemic Clamp; Diagnostic Test: Isoglycemic Intravenous Glucose Test; Diagnostic Test: Hyperinsulinemic Euglycemic Clamp and 2H20 | |
| TT Genotype | Subjects who have not already been tested previously will be tested for the TCF7L2 genotype to determine if they are TT or CC. An anticipated 50 TT subjects will be enrolled in this group. An anticipated 50 obese TT adolescents with IGT or pre-IGT with similar age, pubertal stage, ethnicity and Body Mass Index (BMI) will be enrolled. Subjects will undergo Oral Glucose Tolerance Test, Hyperglycemic Clamp, Isoglycemic Intravenous Glucose Test IsoG IVGT and Hyperinsulinemic Euglycemic Clamp and 2H20 Receives: Diagnostic Test: Oral Glucose Tolerance Test; Diagnostic Test: Hyperglycemic Clamp; Diagnostic Test: Isoglycemic Intravenous Glucose Test; Diagnostic Test: Hyperinsulinemic Euglycemic Clamp and 2H20 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucose tolerance status
An oral glucose tolerance test will be performed to assess glucose tolerance status to determine if subjects are pre-IGT or IGT
Measured: Baseline
Genotype
DNA screening to measure whether subject is CC or TT genotype
Measured: Baseline
Beta cell capacity
AIRmax stimulation test during the hyperglycemic clamp to ascertain the maximal acute insulin response (AIR) to arginine, which is a measure of functional beta cell capacity.
Measured: Baseline
Incretin effect
Subjects will undergo the IsoIVGT test with GLP-1 measurements to measure the incretin effect
Measured: 3weeks to 1 month post Baseline testing
Beta cell function (longitudinally)
The AIRmax stimulation test during the hyperglycemic clamp will be repeated at 2 years to determine if genotype TCF7L2 contributes to worsening in beta cell function longitudinally
Measured: 2 years post Baseline
Hepatic glucose fluxes
Measurements from the Hyperinsulinemic Euglycemic Clamp/ 2H20 Study will be used to assess insulin effects on hepatic glucose production and glycerol kinetics isotopes and the deuterium enrichment at carbons 2 and 5 (C2 and C5) of plasma glucose providing information on glucose fluxes
Measured: 2 months post baseline testing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2017
- Study start1 Mar 2017
- Primary completion31 Aug 2021
- Study completion12 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for IGT - Impaired Glucose ToleranceStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sonia Caprio, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03195400
- Sponsor's protocol ID
- 2000020183
- Other IDs
- 1R01DK111038-01A1
- Status last verified
- Feb 2023
- First submitted
- 22 Mar 2017
- Last updated
- 23 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pathogenesis of Youth Onset Type 2 Diabetes and Prediabetes
- ClinicalTrials.gov ID
- NCT03195400
- Acronym / sponsor ID
- 2000020183
- Conditions
- IGT - Impaired Glucose Tolerance, T2D
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 31 Aug 2021 (actual)
- Study completion
- 12 Aug 2022 (actual)
- First posted
- 22 Jun 2017 (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.
Type 2 Diabetes (T2D) in obese youth is often preceded by a prediabetic state called: Impaired Glucose Tolerance (IGT), which is associated with a pre-existing defect in insulin secretion. This study intends to determine if genetic factors are associated with defects in insulin secretion, the incretin system and hepatic insulin resistance in obese adolescents. The long-term goal of this study is to generate information on both the genetics as well as the pathophysiology of Type 2 Diabetes in Youth, which ultimately might guide the investigators towards better preventive and treatment avenues.
Detailed description
The Specific Aims of this study are:
Aim 1a. To delineate the effects of TCF7L2 rs7903146 on functional Beta-Cell Capacity in obese adolescents with Impaired Glucose Tolerance (IGT) and pre-IGT.
Aim 1b. To determine if the risk genotype in TCF7L2 is associated with worsening in beta cell function longitudinally, thereby affecting changes in glucose tolerance.
Aim 2. To examine the functional effect of the rs7903146 variant in the TCF7L2 gene on a) incretin effect in obese adolescents with IGT and pre-IGT.
Aim 3. To determine the functional effects of TCF7L2 rs7903146 SNP on hepatic glucose fluxes in obese adolescents with IGT and pre-IGT.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CC Genotype | – | Diagnostic Test: Oral Glucose Tolerance Test, Diagnostic Test: Hyperglycemic Clamp, Diagnostic Test: Isoglycemic Intravenous Glucose Test, Diagnostic Test: Hyperinsulinemic Euglycemic Clamp and 2H20Subjects who have not already been tested previously will be tested for the TCF7L2 genotype to determine if they are TT or CC. An anticipated 50 obese CC adolescents with IGT or pre-IGT with similar age, pubertal stage, ethnicity and Body Mass Index (BMI) will enrolled. Subjects will undergo Oral Glucose Tolerance Test, Hyperglycemic Clamp, Isoglycemic Intravenous Glucose Test IsoG IVGT and Hyperinsulinemic Euglycemic Clamp and 2H20. |
| TT Genotype | – | Diagnostic Test: Oral Glucose Tolerance Test, Diagnostic Test: Hyperglycemic Clamp, Diagnostic Test: Isoglycemic Intravenous Glucose Test, Diagnostic Test: Hyperinsulinemic Euglycemic Clamp and 2H20Subjects who have not already been tested previously will be tested for the TCF7L2 genotype to determine if they are TT or CC. An anticipated 50 TT subjects will be enrolled in this group. An anticipated 50 obese TT adolescents with IGT or pre-IGT with similar age, pubertal stage, ethnicity and Body Mass Index (BMI) will be enrolled. Subjects will undergo Oral Glucose Tolerance Test, Hyperglycemic Clamp, Isoglycemic Intravenous Glucose Test IsoG IVGT and Hyperinsulinemic Euglycemic Clamp and 2H20 |
Who may qualify
- Ages
- 12 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Subjects will be selected from the Yale Pediatric Obesity Clinic or from the existing cohort of subjects who have had Oral Glucose Tolerance Tests and genotyping. Subjects will be Pre IGT and IGT adolescents 12-18 years old with either the CC or TT genotype. 50 CC pre IGT/IGT obese patients and 50 TT pre IGT/IGT obese patients will be rectruited.
Key inclusion criteria (7 listed)
- Good general health, taking no medication on a chronic basis;
- Age 12 to 18 yrs, in puberty (girls and boys: Tanner stage II - IV),
- BMI (BMI >85th%) indicating obesity,
- Girls who are menstruating must have a negative pregnancy test during the study and, when possible, be in the follicular phase during infusion study visits (The follicular phase will be identified according to the last menstrual period record and/or according to the oral contraceptive assumption schedule. The investigators will not perform ovulation testing or hormonal assays);
- Subject must have normal liver and kidney function, amylase and lipase levels.
Key exclusion criteria (5 listed)
- Baseline creatinine >1.0 mg;
- Pregnancy;
- Presence of endocrinopathies (e.g. Cushing syndrome);
- Cardiac, renal or pulmonary or other chronic illness;
- Adolescents with psychiatric disorder or with substance abuse history and taking the drugs that affect glucose metabolism, such as any form of steroids, antipsychotics, progesterone preparations, and others.
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 TestAlso: OGTTThe oral glucose tolerance test (OGTT) measures the body's ability to use a type of sugar, called glucose, that is the body's main source of energy. An OGTT can be used to diagnose prediabetes and diabetes. | Diagnostic test | CC Genotype, TT Genotype |
| Hyperglycemic ClampAlso: Infusion StudyTest of beta-cell function and insulin secretion. Involves increasing and maintaining blood glucose concentration with IV variable infusion of dextrose. | Diagnostic test | CC Genotype, TT Genotype |
| Isoglycemic Intravenous Glucose TestAlso: IsoG IVGTTest which exposes pancreas to blood glucose levels matched to the ones obtained at the OGTT. | Diagnostic test | CC Genotype, TT Genotype |
| Hyperinsulinemic Euglycemic Clamp and 2H20Also: E Clamp with labeled waterTest is used to assess insulin effects on hepatic glucose production. | Diagnostic test | CC Genotype, TT Genotype |
Primary outcome
Glucose tolerance status
Time frame: Baseline
An oral glucose tolerance test will be performed to assess glucose tolerance status to determine if subjects are pre-IGT or IGT
Genotype
Time frame: Baseline
DNA screening to measure whether subject is CC or TT genotype
Beta cell capacity
Time frame: Baseline
AIRmax stimulation test during the hyperglycemic clamp to ascertain the maximal acute insulin response (AIR) to arginine, which is a measure of functional beta cell capacity.
Incretin effect
Time frame: 3weeks to 1 month post Baseline testing
Subjects will undergo the IsoIVGT test with GLP-1 measurements to measure the incretin effect
Beta cell function (longitudinally)
Time frame: 2 years post Baseline
The AIRmax stimulation test during the hyperglycemic clamp will be repeated at 2 years to determine if genotype TCF7L2 contributes to worsening in beta cell function longitudinally
Hepatic glucose fluxes
Time frame: 2 months post baseline testing
Measurements from the Hyperinsulinemic Euglycemic Clamp/ 2H20 Study will be used to assess insulin effects on hepatic glucose production and glycerol kinetics isotopes and the deuterium enrichment at carbons 2 and 5 (C2 and C5) of plasma glucose providing information on glucose fluxes
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 23 Feb 2023.
- 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.
Sonia Caprio, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of IGT - Impaired Glucose Tolerance and T2D, run by Yale University 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 7 inclusion and 5 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 23 Feb 2023. 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?
Glucose tolerance status (time frame: Baseline). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Feb 2023.