Diabetes Mellitus, Type 1NCT02663661
Insulin-Glucose-Glucagon Network: Defining a Type 1 Diabetes Progression Index
A study testing Metabolic Challenge Admission and CGM home test in people with Diabetes Mellitus, Type 1, run by University of Virginia at 1 site in United States.
Trial summary
The type 1 Diabetes (T1D) TrialNet Pathway To Prevention (PTP) Study assesses and recruits at-risk subjects into clinical trials aimed at preventing the development of full blown T1D. Read more about this study
- Who is it for?
- Ages 12 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Metabolic Challenge Admission and CGM home test
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Mar 2016to 30 Jun 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 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Individuals 12 to 45 years old which have a brother, sister, child, or parent with type 1 diabetes, or
- Individuals 12-20 years old who have have a cousin, aunt, uncle, niece, nephew, half-brother, half-sister, or grandparent with type 1 diabetes.
Who cannot join
- Have diabetes already (type 1 or type 2)
- Have a medical condition or being been treated with medications that might interfere with the study
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia, Center for Diabetes Technology
Charlottesville, Virginia, 22903
About this study
The type 1 Diabetes (T1D) TrialNet Pathway To Prevention (PTP) Study assesses and recruits at-risk subjects into clinical trials aimed at preventing the development of full blown T1D. Thousands of first and second degree relatives of persons with T1D are screened for autoimmune abnormalities and positive subjects are followed with metabolic and autoantibody tests. The investigators' ancillary study us designed to test whether characterization of the insulin- glucose-glucagon (IGG) interactions in participants in the PTP study can provide new information about the early stages of the disease. When completed, this study will improve the understanding of the pathogenesis of the early stages of T1D and provide new quantitative tools for prediction and evaluation of insulin-glucagon-glucose interactions relevant to individuals at risk for developing T1D, thereby enabling future preventive intervention trials.
Read the detailed description
The goal of the proposed ancillary studies is to establish whether characterization of the insulin-glucagon-glucose (IGG) interactions in first and second degree relatives of patients with type 1 diabetes (T1D) can provide new information about the pathogenesis, prediction, and progression of the early stages of the disease. The project will enroll individuals from the "Living Biobank" of the TrialNet Pathway to Prevention (PTP) study who are phenotyped with respect to a variety of risk factors, including immunological abnormalities. To the best of available knowledge, the IGG relationships in general and the glucagon phenotype in particular have not been studied in this population. It is known, however, that in T1D the release of glucagon is altered, which is manifested by abnormal postprandial suppression and defective response to hypoglycemia. Several reports indicate that glucagon becomes dysregulated prior to the development of T1D, but comprehensive studies aiming to understand in detail the insulin-glucagon co-dynamics in people at risk for T1D have never been performed.
Thus, the goal now is to expand the investigators' existing methodology and transfer expertise in clinical testing and analysis of the IGG system to characterize the IGG interactions in individuals at risk for developing T1D.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Metabolic Challenge Admission, CGM home test
- Keywords
- Diabetes Mellitus, Type 1 (T1DM), TrialNet, Pathway to Prevention (PTP), First and second degree relatives of persons with T1DM, Insulin-glucagon-glucose (IGG), Immunological risk to develop T1DM
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metabolic Challenge AdmissionProcedure or surgery
A ten hour clinical test involving drinking a liquid mixed meal followed four hours later by the induction of hypoglycemia with intravenous insulin administration.
CGM home testOther
A home study starting immediately after the clinical test during which participants will wear a continuous glucose monitor (CGM) for one week.
| Study group | Role | What they receive |
|---|---|---|
| Autoantibody negative subjects | Other | Subjects who are relatives of persons with T1DM and have tested negative for autoantibodies will have a Metabolic Challenge Admission followed by a CGM home test. Receives: Procedure: Metabolic Challenge Admission; Other: CGM home test |
| One autoantibody subjects | Other | Subjects who are relatives of persons with T1DM and have tested positive for one autoantibody will have a Metabolic Challenge Admission followed by a CGM home test.. Receives: Procedure: Metabolic Challenge Admission; Other: CGM home test |
| Two or more autoantibody subjects | Other | Subjects who are relatives of persons with T1DM and have tested positive for two or more autoantibodies will have a Metabolic Challenge Admission followed by a CGM home test.. Receives: Procedure: Metabolic Challenge Admission; Other: CGM home test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Test the hypothesis that immunological abnormalities are associated with abnormally high glucagon responses to a meal and reduced glucagon responses to insulin induced hypoglycemia.
To address this aim, subjects in all three groups which are at different level of immunological risk to develop T1D will undergo a single 10-hour clinical test consisting of a mixed meal drink followed by insulin-induced hypoglycemia (Metabolic Challenge) to estimate their postprandial and counterregulatory glucagon responses.
Measured: Approximately 10 hours
Secondary outcomes (1)
Correlate metrics derived from a minimally-invasive Continuous Glucose Monitor (CGM) home test with glucagon responses to a meal and hypoglycemia measured in the hospital.
Subjects will undergo a CGM home test. They will wear a CGM for a week at home, keep a meal diary, and ingest a mixed meal of known amount with a subsequent collection of urine sample. A novel mathematical methodology will be used to extract from the field data estimates of the glucagon responses to a meal and to a decline in blood glucose levels. It will be then tested whether this estimates correlate to the glucagon responses measured in the hospital.
Measured: Seven days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2016 (estimated)
- Study start16 Mar 2016
- Primary completion30 Jun 2019
- Study completion30 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by University of VirginiaThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Leon Farhi, PhD, University of Virginia
- Investigators
- Leon Farhy, PhD, Principal investigator, UVA Center for Diabetes TechnologySue A Brown, MD, Principal investigator, UVA Center for Diabetes Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02663661
- Sponsor's protocol ID
- 18568
- Other IDs
- DP3DK106907-01
- Status last verified
- Jul 2019
- First submitted
- 7 Dec 2015
- Last updated
- 23 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Montaser E, Breton MD, Brown SA, DeBoer MD, Kovatchev B, Farhy LS. Predicting Immunological Risk for Stage 1 and Stage 2 Diabetes Using a 1-Week CGM Home Test, Nocturnal Glucose Increments, and Standardized Liquid Mixed Meal Breakfasts, with Classification Enhanced by Machine Learning. Diabetes Technol Ther. 2023 Sep;25(9):631-642. doi: 10.1089/dia.2023.0064. Epub 2023 Jun 15.
PubMed 37184602
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Insulin-Glucose-Glucagon Network: Defining a Type 1 Diabetes Progression Index
- ClinicalTrials.gov ID
- NCT02663661
- Acronym / sponsor ID
- 18568
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Diabetes Mellitus, Type 1 (T1DM), TrialNet, Pathway to Prevention (PTP), First and second degree relatives of persons with T1DM, Insulin-glucagon-glucose (IGG), Immunological risk to develop T1DM
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 16 Mar 2016 (actual)
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 30 Jun 2019 (actual)
- First posted
- 26 Jan 2016 (estimated)
- 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.
The type 1 Diabetes (T1D) TrialNet Pathway To Prevention (PTP) Study assesses and recruits at-risk subjects into clinical trials aimed at preventing the development of full blown T1D. Thousands of first and second degree relatives of persons with T1D are screened for autoimmune abnormalities and positive subjects are followed with metabolic and autoantibody tests. The investigators' ancillary study us designed to test whether characterization of the insulin- glucose-glucagon (IGG) interactions in participants in the PTP study can provide new information about the early stages of the disease. When completed, this study will improve the understanding of the pathogenesis of the early stages of T1D and provide new quantitative tools for prediction and evaluation of insulin-glucagon-glucose interactions relevant to individuals at risk for developing T1D, thereby enabling future preventive intervention trials.
Detailed description
The goal of the proposed ancillary studies is to establish whether characterization of the insulin-glucagon-glucose (IGG) interactions in first and second degree relatives of patients with type 1 diabetes (T1D) can provide new information about the pathogenesis, prediction, and progression of the early stages of the disease. The project will enroll individuals from the "Living Biobank" of the TrialNet Pathway to Prevention (PTP) study who are phenotyped with respect to a variety of risk factors, including immunological abnormalities. To the best of available knowledge, the IGG relationships in general and the glucagon phenotype in particular have not been studied in this population. It is known, however, that in T1D the release of glucagon is altered, which is manifested by abnormal postprandial suppression and defective response to hypoglycemia. Several reports indicate that glucagon becomes dysregulated prior to the development of T1D, but comprehensive studies aiming to understand in detail the insulin-glucagon co-dynamics in people at risk for T1D have never been performed.
Thus, the goal now is to expand the investigators' existing methodology and transfer expertise in clinical testing and analysis of the IGG system to characterize the IGG interactions in individuals at risk for developing T1D.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Autoantibody negative subjects | Other | Procedure: Metabolic Challenge Admission, Other: CGM home testSubjects who are relatives of persons with T1DM and have tested negative for autoantibodies will have a Metabolic Challenge Admission followed by a CGM home test. |
| One autoantibody subjects | Other | Procedure: Metabolic Challenge Admission, Other: CGM home testSubjects who are relatives of persons with T1DM and have tested positive for one autoantibody will have a Metabolic Challenge Admission followed by a CGM home test.. |
| Two or more autoantibody subjects | Other | Procedure: Metabolic Challenge Admission, Other: CGM home testSubjects who are relatives of persons with T1DM and have tested positive for two or more autoantibodies will have a Metabolic Challenge Admission followed by a CGM home test.. |
Who may qualify
- Ages
- 12 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Individuals 12 to 45 years old which have a brother, sister, child, or parent with type 1 diabetes, or
- Individuals 12-20 years old who have have a cousin, aunt, uncle, niece, nephew, half-brother, half-sister, or grandparent with type 1 diabetes.
Key exclusion criteria (2 listed)
- Have diabetes already (type 1 or type 2)
- Have a medical condition or being been treated with medications that might interfere with the study
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 |
|---|---|---|
| Metabolic Challenge AdmissionA ten hour clinical test involving drinking a liquid mixed meal followed four hours later by the induction of hypoglycemia with intravenous insulin administration. | Procedure or surgery | Autoantibody negative subjects, One autoantibody subjects, Two or more autoantibody subjects |
| CGM home testA home study starting immediately after the clinical test during which participants will wear a continuous glucose monitor (CGM) for one week. | Other | Autoantibody negative subjects, One autoantibody subjects, Two or more autoantibody subjects |
Primary outcome
Test the hypothesis that immunological abnormalities are associated with abnormally high glucagon responses to a meal and reduced glucagon responses to insulin induced hypoglycemia.
Time frame: Approximately 10 hours
To address this aim, subjects in all three groups which are at different level of immunological risk to develop T1D will undergo a single 10-hour clinical test consisting of a mixed meal drink followed by insulin-induced hypoglycemia (Metabolic Challenge) to estimate their postprandial and counterregulatory glucagon responses.
1 secondary outcome
Correlate metrics derived from a minimally-invasive Continuous Glucose Monitor (CGM) home test with glucagon responses to a meal and hypoglycemia measured in the hospital.
Time frame: Seven days
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 Jul 2019.
- Derived from this study: PubMed 37184602Montaser E, Breton MD, Brown SA, DeBoer MD, Kovatchev B, Farhy LS. Predicting Immunological Risk for Stage 1 and Stage 2 Diabetes Using a 1-Week CGM Home Test, Nocturnal Glucose Increments, and Standardized Liquid Mixed Meal Breakfasts, with Classification Enhanced by Machine Learning. Diabetes Technol Ther. 2023 Sep;25(9):631-642. doi: 10.1089/dia.2023.0064. Epub 2023 Jun 15.
- 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.
Leon Farhy, PhD principal investigator
UVA Center for Diabetes Technology
Sue A Brown, MD principal investigator
UVA Center for Diabetes Technology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Metabolic Challenge Admission and CGM home test in people with Diabetes Mellitus, Type 1, run by University of Virginia 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 2 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 Jul 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?
Test the hypothesis that immunological abnormalities are associated with abnormally high glucagon responses to a meal and reduced glucagon responses to insulin induced hypoglycemia. (time frame: Approximately 10 hours). 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 NCT02663661, which also lists 1 linked publication.
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 Jul 2019.