Clinical trial NCT04362917: Identification of β Cell Dysfunction in Relatives of Individuals With Type 1 Diabetes Mellitus
Official title: Identification of β Cell Dysfunction in Relatives of Individuals With Type 1 Diabetes Mellitus
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 1 Diabetes
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2020-04-27
Enrollment: 70
Sex: ALL
Minimum age (years): 12
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Comparing a population at risk for T1D to healthy controls.

Brief summary: Despite the valuable information derived from older studies evaluating type 1 diabetes, the diabetes research community has, in large part, overlooked potential contributions of baseline abnormalities in β cell function to T1D development. Newer studies focusing on higher risk individuals often exclude family members without evidence of positive islet autoantibodies. New technologies to assay alternative biomarkers of β cell stress and death remain incompletely explored in both Ab negative and Ab positive family members of T1D patients. Specifically, modern biomarkers of β cell dysfunction have not been rigorously tested in combination with metabolic testing to fully understand their association with insulin secretion.

The investigator's working hypothesis is that individuals at genetic risk for T1D exhibit baseline β cell dysfunction, even before development of detectable islet autoimmunity (seropositivity for islet Abs).


Eligibility criteria: Inclusion criteria for each subject group\* note age limits different for each group\*:

* Nonrelative controls: Male and female adults 18-55 years old with no family history of Type 1 Diabetes, who have tested negative for glutamic acid decarboxylase, microinsulin, islet cell, islet antigen 2, and zinc transporter 8 autoantibodies
* Ab negative FDRs: Male and female adults 18-50 years old with a first degree relative (sibling, child, or parent) with T1D, who have tested negative for the above islet autoantibodies
* Ab + T1D Relatives: Male and females aged 12-50 years old with a first or second degree relative diagnosed with T1D, and testing positive for 1 of the above islet autoantibodies either at the screening visit, or through TrialNet screening obtained within the past 12 months.

Criteria for all subjects:

* BMI≤40 kg/m2 (If FDR is 40 kg/m2, the healthy control BMI can not exceed 45 kg/m2)
* HbA1c\< 5.7%
* No medical history of diabetes.

Exclusion criteria for all participants:

* Any type of diabetes or hyperglycemia (HbA1c≥5.7%)
* Chronic illness or use of medications which interfere with glucose or islet hormone metabolism.
* Hemoglobin \< 12 g/dL
* Presence of any psychiatric disorder that will affect the ability to participate in the study
* Pregnancy
* Severe milk or soy allergy that would disallow Boost® ingestion for MMTT
* Any condition that, in the judgment of the investigator, will adversely affect adequate participation in, or the safety or technical performance of the protocol.

Primary outcomes:
measure: Measurement of beta cell function during the first phase of the first clamp procedure
timeFrame: The data for this analysis will come from cross-sectional samples collected through study completion, study completion will be on average 13-16 weeks from visit 1.
Secondary outcomes:
measure: Measurement of beta cell function during of Second Phase of the first clamp procedure
timeFrame: The data for this analysis will come from cross-sectional samples collected through study completion, study completion will be on average 13-16 weeks from visit 1.
Other outcomes:
measure: Measurement of the Unmethylated and methylated DNA as this is a marker of beta cell death
timeFrame: The data for this analysis will come from cross-sectional samples collected through study completion, study completion will be on average 13-16 weeks from visit 1.
measure: Measurement of the Fasting Proinsulin to the C-peptide ratio (PI:C)
timeFrame: The data for this analysis will come from cross-sectional samples collected through study completion, study completion will be on average 13-16 weeks from visit 1.
measure: Test-retest variability of the above mentioned variables (first phase, second phase, Unmethylated and methylated DNA, fasting PI:C
timeFrame: The data for this analysis will come from cross-sectional samples collected through study completion, study completion will be on average 13-16 weeks from visit 1.
Locations:
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
Study officials:
affiliation: Indiana University
name: Emily Sims
role: PRINCIPAL_INVESTIGATOR
References: