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Insulin-Glucose-Glucagon Network: Defining a Type 1 Diabetes Progression Index

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ClinicalTrials.gov Identifier: NCT02663661
Recruitment Status : Recruiting
First Posted : January 26, 2016
Last Update Posted : March 25, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Leon Farhi, PhD, University of Virginia

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Procedure: Metabolic Challenge Admission Other: CGM home test Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Insulin-Glucose-Glucagon Network: Defining a Type 1 Diabetes Progression Index
Study Start Date : February 2016
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Autoantibody negative subjects
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.
Procedure: Metabolic Challenge Admission
A ten hour clinical test involving drinking a liquid mixed meal followed four hours later by the induction of hypoglycemia with intravenous insulin administration.

Other: CGM home test
A home study starting immediately after the clinical test during which participants will wear a continuous glucose monitor (CGM) for one week.

One autoantibody subjects
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..
Procedure: Metabolic Challenge Admission
A ten hour clinical test involving drinking a liquid mixed meal followed four hours later by the induction of hypoglycemia with intravenous insulin administration.

Other: CGM home test
A home study starting immediately after the clinical test during which participants will wear a continuous glucose monitor (CGM) for one week.

Two or more autoantibody subjects
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..
Procedure: Metabolic Challenge Admission
A ten hour clinical test involving drinking a liquid mixed meal followed four hours later by the induction of hypoglycemia with intravenous insulin administration.

Other: CGM home test
A home study starting immediately after the clinical test during which participants will wear a continuous glucose monitor (CGM) for one week.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  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. [ Time Frame: Seven days ]
    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.



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Ages Eligible for Study:   12 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Have diabetes already (type 1 or type 2)
  • Have a medical condition or being been treated with medications that might interfere with the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02663661


Contacts
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Contact: Ryan McFadden, MSN, BA, RN, CNL 434-924-7164 rkm2f@virginia.edu

Locations
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United States, Virginia
University of Virginia, Center for Diabetes Technology Recruiting
Charlottesville, Virginia, United States, 22903
Contact: Jennifer Puskaric, RN    434-924-71643    jlw5k@virginia.edu   
Contact: Mary Oliveri, MS, CCRP    434-960-6818    mc7m@virginia.edu   
Sub-Investigator: Boris Kovatchev, Ph.D.         
Sub-Investigator: Marc Breton, Ph.D.         
Sub-Investigator: Mark DeBoer, MD, MSc., MCR         
Sub-Investigator: Anthony McCall, MD, PhD         
Sub-Investigator: Daniel Cherñavvsky, MD, CRC         
Sub-Investigator: Stephen Patek, PhD         
Sub-Investigator: Christian Wakeman, M.S.         
Sponsors and Collaborators
University of Virginia
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Leon Farhy, PhD UVA Center for Diabetes Technology
Principal Investigator: Sue A Brown, MD UVA Center for Diabetes Technology

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Responsible Party: Leon Farhi, PhD, Principal Investigator, University of Virginia
ClinicalTrials.gov Identifier: NCT02663661     History of Changes
Other Study ID Numbers: 18568
DP3DK106907-01 ( U.S. NIH Grant/Contract )
First Posted: January 26, 2016    Key Record Dates
Last Update Posted: March 25, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Leon Farhi, PhD, University of Virginia:
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

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucagon-Like Peptide 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Insulin, Globin Zinc
Glucagon
Autoantibodies
Hypoglycemic Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Incretins
Immunologic Factors