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STOP-T1D Low-Dose (ATG) (TN28)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04291703
Recruitment Status : Recruiting
First Posted : March 2, 2020
Last Update Posted : December 15, 2023
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary:
A multi-center, placebo-controlled, double blind, 2:1 randomized control clinical trial testing low-dose ATG vs. placebo in subjects with a 2 year 50% risk of progression to stage 3 T1D.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Antithymocyte Globulin Drug: Placebo (for ATG) Phase 2

Detailed Description:
This study has an enrollment period of three years and once the enrollment phase has concluded, an additional two years of follow-up visits will be conducted for all participants. Participants enrolled in the first year of the study can expect to complete follow-up visits for approximately four additional years if progression to stage 3 (Type 1 Diabetes Onset) does not occur. Participant follow-up visits after the treatment phase of the study includes general assessments (medical history, physical exam, medications and adverse events) and laboratory assessments to determine current health status and glucose tolerance.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 114 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Eligible study participants will be randomized in a 2:1 allocation to either ATG vs. placebo treatment arms by the TrialNet Coordinating Center at the baseline visit once eligibility has been confirmed. Randomization will be conducted using block randomization with variable block sizes with stratification on TrialNet study site and age group (< 12 years old vs. 12 years old or older). Subjects will be assigned a study randomization number corresponding to the treatment group assignment.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: The randomization method will be stratified by TrialNet study site. The participants will not be informed regarding the intervention assignment until the end of the study. The investigator and clinic personnel will also be masked as to study assignment. Laboratories performing assays for this protocol will be masked as to the identity of biological material to be studied.
Primary Purpose: Prevention
Official Title: Low Dose Antithymocyte Globulin (ATG) to Delay or Prevent Progression to Stage 3 T1D
Actual Study Start Date : January 1, 2023
Estimated Primary Completion Date : December 31, 2028
Estimated Study Completion Date : December 31, 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: Antithymocyte globulin (ATG)
Antithymocyte globulin (ATG) will be intravenously administered over two days, with a total of 2 infusion periods. The first infusion is given at baseline visit (day 1), the second is given the next day at baseline visit (day 2). Body weight at baseline (Day 0- admission for the ATG/placebo infusion) will be used in calculating the doses for all infusions. The first dose (0.5mg/kg) will be infused over a minimum of 4 hours, and the second dose (2mg/kg) over a minimum of 4 hours with a maximum infusion time for each infusion of 10 hours. The second dose should be given no less than 12 and no more than 30 hours from the start of the first infusion. The final prepared product is to be labeled to protect the blind. Infusions may be administered either in a hospital or outpatient setting at the investigator's or institutions discretion.
Drug: Antithymocyte Globulin
Thymoglobulin
Other Name: Thymoglobulin

Placebo Comparator: Placebo
0.9% Sodium Chloride Injection USP ("Normal" saline) is to be dispensed as the placebo for this study. The placebo is to be prepared dispensing an infusion bag of 0.9% Sodium Chloride Injection USP ("Normal" saline) with no additives (no ATG, no premedications) and label the product to protect the blind. The placebo will also be administered over a minimum of 4 hours for the first and second doses with a maximum infusion time of 10 hours. The second dose of the placebo arm should be given no less than 12 and no more than 30 hours from the start of the first infusion. Infusions may be administered either in a hospital or outpatient setting at the investigator's or institutions discretion.
Drug: Placebo (for ATG)
Normal Saline administered by IV infusion to mimic ATG




Primary Outcome Measures :
  1. Progression to Stage 3 T1D [ Time Frame: 5 years ]
    The primary outcome is the elapsed time from random treatment assignment to the development of diabetes or time of last contact among those randomized



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 34 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing to provide informed consent or have a parent or legal guardian provide informed consent when the subject is <18 years of age.
  2. Age greater than or equal to 12 and < 35 years
  3. At least two or more diabetes-related biochemical autoantibodies (mIAA, GADA, ICA, IA-2A, ZnT8A) present on the same sample. In the absence of other antibodies, ICA and GADA positivity alone will not suffice for eligibility in this trial.
  4. Weight greater than the 5th percentile for age and sex.
  5. BMI < 95th and > 5th percentile for age for those under age 18 years and < 30 and > 15 for adults (≥ 18)
  6. ADA Stage 2 criteria* AND at least one of the following high-risk markers (occurring at the same visit) within 7 weeks (52 days) of randomization, defined below (for defining a 2-year 50% risk for progression to Stage 3 T1D):

    a. HbA1c ≥ 5.7 and <6.5% b. Index60 ≥ 1.4 i. Index60 = 0.3695 × (log fasting C-peptide [ng/mL]) + 0.0165 × 60-min glucose (mg/dL) - 0.3644 × 60-min C-peptide (ng/mL) c. DPTRS ≥ 7.4 DPTRS = (1.57 x log BMI) - (0.06 x age) + (0.81 x glucose sum from 30 to 120 min/100) - (0.85 x C-peptide sum from 30 to 120 min/10) + (0.48 x log fasting C-peptide)

    *Dysglycemia is defined as 2-hr glucose ≥ 140 and <200 mg/dL or fasting glucose ≥ 110 and <126

  7. All subjects must be CMV and EBV PCR negative within 30 days of randomization and may not have had signs or symptoms of a CMV or EBV-compatible illness lasting longer than 7 days within 30 days of randomization
  8. Seated blood pressure less than 130/80 mmHg for participants ≥ 18 years. For participants < 18 years seated blood pressure less than 95th percentile for age, sex and height.
  9. Be at least 4 weeks from last live immunization
  10. Participants are required to receive non-live influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available.
  11. Participants are required to receive an authorized non-live COVID-19 vaccination and be fully vaccinated, including eligible boosters at least two weeks prior to randomization. Participants must also have a negative COVID-19 PCR test within 3 days of the first day of treatment.
  12. Willingness to comply with study directed social distancing and protection from SARS-Cov-2 infection.
  13. Be willing to forgo vaccines (other than killed influenza) during the 3 months after study drug treatment period (Days 0 and 1)
  14. Be up to date on all recommended vaccinations based on age of subject*
  15. With the exception of stage 2 T1D, subjects must be healthy, as defined by absence of any other untreated diagnoses that the protocol committee deems to be a potential confounder.
  16. If a female participant with reproductive potential, willing to avoid pregnancy (abstinence or adequate contraceptive method) through the completion of the study infusions and up to 3 months after study drug administration and undergo pregnancy testing prior to each study visit.
  17. Must be residing or have accommodations within 1 hour of the infusion site during the two days of study drug infusions and must be within 1 hour of a medical care facility for 1 day after completion of infusion 2.
  18. Participants must live in a location with rapid access to emergency medical services.

    • Adult subjects must be fully immunized. Pediatric subjects who have not completed their primary vaccination schedule must receive all vaccinations allowable per the AAP immunization guidelines for their current age prior to study drug delivery. Any remaining vaccinations should be given and continue per the schedule at least 3 months after study drug is administered.

Exclusion Criteria:

  1. Immunodeficiency or clinically significant chronic lymphopenia: (Leukopenia (< 3,000 leukocytes /μL), neutropenia (<1,500 neutrophils/μL), lymphopenia (<800 lymphocytes/μL), thrombocytopenia (<100,000 platelets/μL).
  2. Hemoglobin less than 13.5 g/dL for adult men and less than 12 g/dL for adult females and less than 11 g/dL for participants under age 18
  3. Active signs or symptoms of acute infection at the time of randomization including SARS-Cov-2.
  4. Uncontrolled autoimmune thyroid disease and/or celiac disease (participants must be well controlled for the previous 6 months).
  5. Evidence of prior or current tuberculosis infection as assessed interferon gamma release assay (QuantiFERON).
  6. Currently pregnant or lactating or anticipate getting pregnant within the study period.
  7. Require use of other immunosuppressive agents including chronic use of systemic steroids.
  8. Evidence of current or past HIV or Hepatitis B or current Hepatitis C infection.
  9. Any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk to include pre-existing cardiac disease, COPD, sickle cell disease, neurological disease, or blood count abnormalities.
  10. A history of malignancies other than of skin.
  11. Evidence of liver dysfunction with AST or ALT outside of the reference range.
  12. Evidence of renal dysfunction with creatinine outside of the reference range.
  13. Increased bilirubin (total and direct) outside of the normal limit (Participants with documentation of Gilbert's Disease permitted).
  14. Vaccination with a live virus within the last 4 weeks.
  15. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within 7 days of screening
  16. Prior treatment with Teplizumab (either in a previous clinical trial or clinically).
  17. Has participated in a clinical trial for diabetes prevention previously and received active study agent within 3 months of randomization.
  18. Known allergy to ATG
  19. Prior treatment with ATG or known allergy to rabbit-derived products
  20. Prior adverse reactions to heparin.
  21. Any condition that in the investigator's opinion may adversely affect study participation will be reviewed by the Study Chair to ensure consistency and adjudicate whether or not the subject may compromise the study results
  22. Any screening/baseline laboratory result not otherwise stated out of normal reference range and/or medical history that may increase the risk of the subject's participation in this trial.
  23. Previously diagnosed with Stage 3 TID according to ADA criteria76 (see Appendix 3 for Criteria for diagnosis of diabetes)

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): NCT04291703


Contacts
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Contact: Melissa A Parker, MHA 8133969378 MELISSA.PARKER@EPI.USF.EDU
Contact: Ryan O'Donnell 8133969551 Ryan.O'Donnell@epi.usf.edu

Locations
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United States, California
University of California - San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Rebecca Wesch    415-476-5984    rebecca.wesch@ucsf.edu   
Contact: Karen Ko    415-514-3730    karen.ko@ucsf.edu   
Principal Investigator: Stephen Gitelman, MD         
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Trudy Esrey    650-498-4450    tesrey@stanford.edu   
Principal Investigator: Darrell Wilson, MD         
United States, Colorado
Barbara Davis Center at University of Colorado Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Morgan Sooy, RN    303-724-5686    MORGAN.SOOY@CUANSCHUTZ.EDU   
Principal Investigator: Kimberly Simmons, MD         
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06511
Contact: Lori Carria    203-737-3595    lori.carria@yale.edu   
Principal Investigator: Jennifer L. Sherr, MD         
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Danielle Poulton    352-294-5762    danielle.poulton@peds.ufl.edu   
Contact: Jennifer Hosford    352-294-5759    jennifer.hosford@peds.ufl.edu   
Principal Investigator: Michael Haller, MD         
United States, Indiana
Indiana University - Riley Hospital for Children Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Maria Spall    317-278-8879    malnicho@iu.edu   
Principal Investigator: Linda DiMeglio, MD         
United States, Iowa
Children's Hospital of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Carter Johnson    319-335-7434    carter-johnson-1@uiowa.edu   
Principal Investigator: Michael Tansey, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Kali Johnson    612-624-6682    joh13933@umn.edu   
Principal Investigator: Toni Moran, MD         
United States, Missouri
The Children's Mercy Hospital Recruiting
Kansas City, Missouri, United States, 64108
Contact: Heather Harding    816-960-8985    hrharding@cmh.edu   
Principal Investigator: Wayne Moore, MD         
United States, New York
Columbia University-Naomi Berrie Diabetes Center Recruiting
New York, New York, United States, 10032
Contact: Nathan Schwab    212-851-5460    ns3700@cumc.columbia.edu   
Principal Investigator: Robin Goland, MD         
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Kelli DeLallo    412-692-5210    kelli.delallo@chp.edu   
Principal Investigator: Ingrid Libman, MD         
United States, Tennessee
Vanderbilt Eskind Diabetes Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Brenna Hammel    615-337-9597    brenna.hammel@vumc.org   
Principal Investigator: William Russell, MD         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Michelle Murphy    214-456-9238    michelle.murphy@utsouthwestern.edu   
Principal Investigator: Perrin White, MD         
United States, Washington
Benaroya Research Institute Recruiting
Seattle, Washington, United States, 98101
Contact: Kate Bennett    206-341-8945    kbennett@benaroyaresearch.org   
Principal Investigator: Sandra Lord, MD         
Australia, Victoria
Walter and Eliza Hall Institute of Medical Research Recruiting
Melbourne, Victoria, Australia, 3050
Contact: Felicity Healy    9342-7063    felicity.healy@mh.org.au   
Contact: Leanne Redl    61 3 9342 7063    leanne.redl@mh.org.au   
Principal Investigator: John Wentworth, MD         
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Additional Information:
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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT04291703    
Other Study ID Numbers: TrialNet TN28
UC4DK117009 ( U.S. NIH Grant/Contract )
First Posted: March 2, 2020    Key Record Dates
Last Update Posted: December 15, 2023
Last Verified: October 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be available at the NIDDK Central Repository

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
TrialNet
T1D
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Thymoglobulin
Antilymphocyte Serum
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents