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Abnormal Glucose TolerancePhase 2NCT01773707

CTLA4-Ig (Abatacept)for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives At -Risk for Type 1

A Phase 2 study testing CTLA4-Ig (Abatacept) in people with Abnormal Glucose Tolerance and Type 1 Diabetes, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 17 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The study is a 2-arm, multicenter, 1:1 randomized, placebo controlled clinical trial. All subjects will receive close monitoring for development of AGT or T1DM. Subjects will receive Abatacept or placebo and close monitoring for development of AGT or T1DM. Read more about this study

Who is it for?
Ages 6 to 45 years
Conditions the study is for
Abnormal Glucose Tolerance, Type 1 Diabetes
What is being tested?
CTLA4-Ig (Abatacept)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
212 participants
Where
17 sitesin 2 countries
Study dates
Mar 2013to 14 Dec 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 6 to 45 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Participant in TrialNet Natural History/Pathway to Prevention Study and thus, a relative of a proband with T1DM.
  • Between the ages of 1-45 years at the time of enrollment in TN01 and age ≥ 6 at time of randomization in this trial.
  • Willing to provide Informed Consent or have a parent or legal guardian provide informed consent if the subject is <18 years of age.
  • Normal glucose tolerance by OGTT confirmed within 7 weeks (no more than 52 days) of baseline (visit 0). If previous abnormal glucose tolerance, has had two consecutive OGTTs with normal glucose tolerance.
  • Fasting plasma glucose < 110 mg/dL (6.1 mmol/L), and
  • 2 hour plasma glucose <140 mg/dL (7.8 mmol/L), and
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  • 30, 60, or 90 minute value on OGTT< 200mg/dL (11.1 mmol/L)
  • At least two diabetes-related autoantibodies confirmed to be present on two occasions, not including mIAA. Confirmation of 2 positive autoantibodies must occur within the six months prior to randomization, but the confirmation does not have to involve the same 2 autoantibodies.
  • Weight ≥ 20 kg at Baseline Visit.
  • If a female participant with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing prior to each infusion.
  • At least three months from date of last live immunization.
  • Willing to forgo live vaccines while receiving treatment on study and for three months following last study drug administration.

Who cannot join

  • Abnormal Glucose Tolerance or Diabetes
  • Fasting plasma glucose ≥ 110 mg/dL (6.1 mmol/L), or
  • 2 hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L), or
  • 30, 60, 90 minute plasma glucose during OGTT ≥ 200 mg/dL (11.1 mmol/L)
  • Insulin autoantibodies (mIAA).
  • Are immunodeficient or have clinically significant chronic lymphopenia.
Show all 15Show fewer
  • Have an active infection at time of randomization.
  • Have a positive PPD test result or history of previously treated TB, or positive interferon-gamma release assay (IGRA) test.
  • Be currently pregnant or lactating, or anticipate getting pregnant within 3 months of the last study drug administration.
  • Use of medications known to influence glucose tolerance.
  • Require use of other immunosuppressive agents.
  • Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B core antibody or surface antigen), or Hepatitis C infection.
  • Have serological evidence of current CMV infection.
  • Have evidence of active EBV infection.
  • Have any complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk. These include pre-existing cardiac disease, COPD, neurological, or blood count abnormalities (such as lymphopenia, leukopenia, or thrombocytopenia).

Trial locations and contacts

17 sites in 2 countries.

17 sites in 2 countries

United States16 sites
  • University of Chicago

    Chicago, Illinois, 60637

  • University of Texas Medical Center at Dallas

    Dallas, Texas, 75390-8858

  • Barbara Davis Center for Childhood Diabetes, University of Colorado

    Denver, Colorado, 80262

  • University of Florida

    Gainesville, Florida, 32610-

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Indiana University-Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • University of Miami School of Medicine

    Miami, Florida, 33136

  • University of Minnesota

    Minneapolis, Minnesota, 57931

  • Vanderbilt University

    Nashville, Tennessee

  • Yale Medical School

    New Haven, Connecticut

  • Columbia University

    New York, New York

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15213

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • University of California - San Francisco

    San Francisco, California, 94143

  • Benaroya Research Institute at Virginia Mason

    Seattle, Washington, 98101

  • Stanford University Medical Center

    Stanford, California, 94305-5208

Other trials in United States

Canada1 site
  • The Hospital for Sick Children

    Toronto, Ontario, MSG-1X8

Other trials in Canada

About this study

Official title: CTLA4-Ig (Abatacept)for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives At -Risk for Type 1 Diabetes

The study is a 2-arm, multicenter, 1:1 randomized, placebo controlled clinical trial.

All subjects will receive close monitoring for development of AGT or T1DM. Subjects will receive Abatacept or placebo and close monitoring for development of AGT or T1DM. To assess the safety, efficacy, and mode of action of Abatacept to prevent AGT and T1DM.

Read more

The primary objective is to determine whether intervention with Abatacept will prevent or delay the development of AGT in at-risk autoantibody positive non-diabetic relatives of patients with T1DM.

Secondary outcomes include: the effect of Abatacept on the incidence of T1DM; analyses of C-peptide and other measures from the OGTT; safety and tolerability; and mechanistic outcomes.

Read the detailed description

Study Purpose and Rationale:

In this study, relatives who are confirmed to have two or more antibodies, not including mIAA, and normal glucose tolerance will be eligible for randomization to experimental treatment or placebo groups with the aim to determine whether experimental treatment will prevent or delay the occurrence of abnormal glucose tolerance and type 1 diabetes mellitus. Individuals with normal glucose tolerance are earlier in the disease process; that is, have less beta cell destruction than those with abnormal glucose tolerance or frank diabetes, yet will inevitably progress to clinical disease and essentially complete beta cell loss. Treatment at this early stage in a population who will inevitably progress to type 1 diabetes provides the greatest opportunity for a clinically important impact on disease prevention. With abnormal glucose tolerance rather than diabetes as the primary endpoint, study participants, regulators, funders, and investigators will be able to determine whether the therapy can alter disease progression.

Therefore, the rationale for this study is that individuals with immunologic markers of T1DM and normal glucose tolerance will inevitably develop clinical T1DM. Prior to development of clinical T1DM they will progress from normal glucose tolerance to abnormal glucose tolerance; and abnormal glucose tolerance results in clinical T1DM within 5 years in almost 80% of subjects. They have a condition that differs from overt diabetes only in the duration of the autoimmune process that results in beta cell destruction. Intervention early in the course of disease may be more effective than intervention in those with abnormal glucose tolerance or clinical T1DM.

Description of Treatment Groups

Subjects will be randomized to receive either Abatacept or placebo infusions along with close monitoring for abnormal glucose tolerance or diabetes. The infusions will be conducted at approved TrialNet clinical sites with appropriate facilities. All blood and serum samples for the primary and secondary outcome determinations will be sent to the Core Laboratories for analysis. Clinical laboratory studies may be done at the local sites.

Participants will be randomly assigned in a 1:1 ratio (within the two strata defined by age at enrollment: <18 and 18 or older) to the following 2 groups:

  • to receive Abatacept (intravenous infusion at 0, 2, and 4 weeks following randomization, and then every 28+/-7 days) thereafter for a total of 14 doses. Close monitoring for diabetes development through the duration of study.
  • to receive placebo intravenous infusion at 0, 2, and 4 weeks following randomization and then every 28+/- 7 days thereafter for a total of 14 doses. Close monitoring for diabetes development through the duration of study.

Treatment Assignment

After participants sign the consent form, complete the screening visit(s), and meet all of the inclusion criteria and none of the exclusion criteria, participants will be randomized to receive either Abatacept and close monitoring or placebo with close monitoring.

Participants will be randomized in equal allocations to each group. The randomization method will be stratified by TrialNet study site and whether the participant is less than 18 years of age or 18 years and older. This approach ensures that study site will not be a potential confounder. The TNCC will generate the randomization numbers and tables.

Study Assessments

During the course of the study, participants will frequently undergo assessments of their glucose tolerance status, insulin production, immunologic status, and overall health and well-being.

Samples will be drawn for storage in the National Institute for Diabetes and Digestive and Kidney Disease (NIDDK) Repository and at TrialNet Laboratory Sites for future analysis related to T1DM.

Study Duration

The study has been designed to provide 80% power to detect a 40% risk reduction in the occurrence of abnormal glucose tolerance using a two-sided test at the 0.05 level after six years of study duration. A total of approximately 206 patients will be allocated in a 1:1 ratio to the two groups.

Being tested
CTLA4-Ig (Abatacept), Placebo
Keywords
prevention of type 1 diabetes, prevention of abnormal glucose tolerance
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CTLA4-Ig (Abatacept)Drug

    Also called Abatacept

    Given as 30 minute IV infusion

  • PlaceboDrug

    Saline given as 30 minute IV infusion

Study groups in NCT01773707
Study groupRoleWhat they receive
abatacept IV infusionExperimentalCTLA4-Ig (Abatacept) will be administered as 14 (30 minute) infusions over one year (3 infusions every other week the first month; monthly for the following 11 months)
Receives: Drug: CTLA4-Ig (Abatacept)
PlaceboPlacebo comparatorThe placebo arm will receive 14 (30 minute) IV infusions (containing saline) given 3 times (every other week) the first month and monthly for the following 11 months.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time From Randomization to Confirmed Abnormal Glucose Tolerance Test

    Measured by Oral Glucose Tolerance Test (OGTT):

    Abnormal Glucose Tolerance is primary endpoint and defined as:

    1. Fasting plasma glucose ≥ 110 mg/dL (6.1 mmol/L) and < 126 mg/dL (7 mmol/L), or
    2. 2 hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L) and < 200 (11.1 mmol/L), or
    3. 30, 60, 90 minute plasma glucose during OGTT ≥ 200 mg/dL (11.1 mmol/L)

    Measured: 96 months

Secondary outcomes (1)
  1. Change in C-peptide Concentration to Oral Glucose Tolerance Test (OGTT)

    To Determine whether treatment with Abatacept is superior to placebo with respect to C-peptide response to oral glucose tolerance

    Measured: 0 time to 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2013 (estimated)
  2. Study startMar 2013
  3. Primary completion14 Dec 2021
  4. Study completion14 Dec 2022

Resources

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 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
212 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01773707
Sponsor's protocol ID
Abatacept (IND)
Other IDs
UC4DK106993, UC4DK117009
Status last verified
Jul 2023
First submitted
10 Jan 2013
Last updated
6 Jun 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Orban T, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, Gottlieb PA, Greenbaum CJ, Marks JB, Monzavi R, Moran A, Raskin P, Rodriguez H, Russell WE, Schatz D, Wherrett D, Wilson DM, Krischer JP, Skyler JS; Type 1 Diabetes TrialNet Abatacept Study Group. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet. 2011 Jul 30;378(9789):412-9. doi: 10.1016/S0140-6736(11)60886-6. Epub 2011 Jun 28.

    PubMed 21719096
  • Leung SS, Borg DJ, McCarthy DA, Boursalian TE, Cracraft J, Zhuang A, Fotheringham AK, Flemming N, Watkins T, Miles JJ, Groop PH, Scheijen JL, Schalkwijk CG, Steptoe RJ, Radford KJ, Knip M, Forbes JM. Soluble RAGE Prevents Type 1 Diabetes Expanding Functional Regulatory T Cells. Diabetes. 2022 Sep 1;71(9):1994-2008. doi: 10.2337/db22-0177.

    PubMed 35713929

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CTLA4-Ig (Abatacept) in people with Abnormal Glucose Tolerance and Type 1 Diabetes, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 17 sites in 2 countries.

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 12 inclusion and 15 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 6 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Canada. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Time From Randomization to Confirmed Abnormal Glucose Tolerance Test (time frame: 96 months). 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 NCT01773707, which also lists 2 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 6 Jun 2024.

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