ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    DIPIT
Previous Study | Return to List | Next Study

Diabetes Islet Preservation Immune Treatment (DIPIT)

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: NCT02586831
Recruitment Status : Not yet recruiting
First Posted : October 26, 2015
Last Update Posted : July 12, 2018
Sponsor:
Collaborator:
Diabetes Research Institute Foundation
Information provided by (Responsible Party):
Camillo Ricordi and Jay Skyler, University of Miami

Brief Summary:
To assess whether there is a difference in endogenous insulin secretion, measured as stimulated C-peptide secretion (area under the curve during a 4-hour mixed meal tolerance test), at the 1 year visit, for study subjects receiving combinational therapy versus those receiving placebo. The study will also examine the effect of the proposed treatments on immunological outcomes, specifically proportion of regulatory T cells at the 1 year visit.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Hypoglycemia Autoimmune Diseases Diabetes Mellitus Drug: Anti-Thymocyte Globulin (ATG) Drug: Placebo Drug: Pegylated GCSF Drug: Interleukin 2 Drug: Etanercept Drug: Exenatide Phase 1 Phase 2

Detailed Description:
There is a critical need to test therapies that afford long-lasting immunomodulation through the combined use of short courses of depleting agents, more chronic use of drugs that promote immunoregulation and critically control the rebounding effector populations, together with interventions that quell inflammation and support beta cell function and glucose metabolism. Such combined regimens would rely on lower doses of many of these agents, for increased safety and tolerability. Here, we propose a combinatorial regimen based on the administration of drugs that are already FDA approved and marketed, all of which have been used in clinical trials in patients with T1D, alone or in some combination. This trial will test if the regimen proposed, for the first time combining all of these agents, will be successful in preserving insulin secretion in recent onset type 1 diabetes.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Pilot, Safety and Feasibility Trial of Anti-Thymocyte Globulin (ATG), Pegylated Granulocyte Colony Stimulating Factor (GCSF), Low Dose Interleukin-2 (IL-2), Etanercept and Exenatide in the Treatment of New Onset Type 1 Diabetes
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm A

The treatment arm A includes commercially available drugs approved for other indications:

  • Anti-Thymocyte Globulin (ATG or Thymoglobulin®) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg (day 0 and 1).
  • Pegylated GCSF (Neulasta®) will be administered at a dose of 6mg SC every two weeks for a total of 6 doses (Day 2, 14, 28, 42, 56, and 70).
  • Low-dose Interleukin 2 (Aldesleukin; IL-2 or Proleukin®), 1 million IU/dose will be given SC for 5 consecutive days (days 10-14), and then every two weeks.
  • Etanercept (Enbrel®) will be administered at a dose of 25 mg SC weekly up to 52 weeks.
  • Exenatide (Bydureon®): 2 mg SC weekly up to 52 weeks; Adjust according to symptoms.
Drug: Anti-Thymocyte Globulin (ATG)
Concomitant Drug Administration
Other Name: Thymoglobulin

Drug: Pegylated GCSF
Concomitant Drug Administration
Other Name: Neulasta

Drug: Interleukin 2
Concomitant Drug Administration
Other Name: Aldesleukin; IL-2 or Proleukin®

Drug: Etanercept
Concomitant Drug Administration
Other Name: Enbrel®

Drug: Exenatide
Concomitant Drug Administration
Other Name: Bydureon®

Placebo Comparator: Arm B
The subjects randomized in Arm B (control group) will receive respective placebos in a blinded fashion.
Drug: Placebo
Drug Administration




Primary Outcome Measures :
  1. Stimulated C-peptide AUC from a 4-hour MMTT [ Time Frame: 1 Year Visit ]

    The primary statistical hypothesis to be assessed in this study is whether there is a difference in endogenous insulin secretion, measured as stimulated C-peptide secretion (area under the curve during a 4-hour mixed meal tolerance test), at the 1 year visit, for study subjects receiving combinational therapy versus those receiving placebo.

    The study will also examine the effect of the proposed treatments on immunological outcomes, specifically proportion of regulatory T cells at the 1 year visit.




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.


Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must meet all of the following criteria to be eligible to participate in this study:

    1. Subject must be able to understand and provide informed consent.
    2. Males and females, 18-35 years of age.
    3. New onset T1D for no longer than 120 days at the time of randomization.
    4. Affected by T1D, according to ADA standard criteria, and confirmed by positivity of at least one T1D-associated autoantibody, to GAD65, IA-2, ZnT8, or insulin autoantibodies (if patient has been treated with insulin for less than 2 weeks).
    5. Being on insulin therapy.
    6. Stimulated C-peptide peak level >0.2 nmol/L at the baseline 1 visit MMTT.
    7. Female subjects of childbearing potential must have a negative pregnancy test upon study entry.
    8. Female (and male) subjects with reproductive potential must agree to use two FDA approved methods of birth control for the entire duration of the study.
    9. Adequate venous access to support study required blood draws.

Exclusion Criteria:

  • Potential participants must not meet any of the following exclusion criteria:

    1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
    2. BMI>30 Kg/m2.
    3. Contra-indications to ATG, GCSF, exenatide, etanercept and IL-2 (as per package insert, e.g., knowledge of hypersensitivity to drugs or its excipients).
    4. Uncompensated heart failure, fluid overload, myocardial infarction or liver disease or severe impairment of a vital organ within the last 6 weeks before enrollment.
    5. Any of the following laboratory findings: hemoglobin <10.0 g/dL; leukocytes <3,000/μL; neutrophils <1,500/μL; lymphocytes <800/μL; platelets <100,000/μL.
    6. Any sign or diagnosis of significant chronic active infection (e.g., hepatitis, tuberculosis, EBV, or CMV), or screening laboratory evidence consistent with a significant chronic active infection (such as positive for HIV, IGRA test for TB, or hepatitis B-C).
    7. Ongoing acute infections, e.g., acute respiratory tract urinary tract, or gastrointestinal tract infections.
    8. Ongoing or anticipated use of diabetes medications other than insulin.
    9. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within prior 7 days of screening.
    10. Current or prior use of immunomodulators or systemic steroids in the last 2 months that could potentially affect diabetes or immunologic status.
    11. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 6 weeks of randomization.
    12. Use of investigational drugs within 3 months of participation.
    13. Concomitant therapy with immunosuppressive drugs, immunomodulators, or cytotoxic agents, or previous therapy less than 3 months from randomization.
    14. History or diagnosis of malignancy. Any history of gastroparesis or other severe gastrointestinal disease, pancreatitis, thyroid nodules or malignancy with the exception of a history of localized basal cell carcinoma.
    15. Presence of an allograft.
    16. AST, ALT or Alkaline Phosphatase >2 times upper limit of normal or total bilirubin >1.5 times upper limit of normal.
    17. Current, diagnosed, mental illness or current, diagnosed or self-reported drug or alcohol abuse; or any situation that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
    18. Pregnancy or ongoing breastfeeding for women; unwillingness or inability of both females and males of childbearing age to use a reliable and effective form of contraception, for the entire duration of the study.
    19. Past or current medical problems, or findings from physical examination, or laboratory testing, that are not listed above which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained.

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): NCT02586831


Contacts
Contact: Rodolfo Alejandro, M.D. (305) 243-5324 ralejand@med.miami.edu
Contact: David A Baidal, M.D. (305) 243-7740 dbaidal@med.miami.edu

Locations
United States, Florida
Diabetes Research Institute, University of Miami Miller School of Medicine Not yet recruiting
Miami, Florida, United States, 33136
Contact: Rodolfo Alejandro, M.D.    305-243-5324    ralejand@med.miami.edu   
Contact: David A Baidal, M.D.    (305) 243-7740    dbaidal@med.miami.edu   
Principal Investigator: Rodolfo Alejandro, M.D.         
Principal Investigator: David A Baidal, M.D.         
Sponsors and Collaborators
Camillo Ricordi and Jay Skyler
Diabetes Research Institute Foundation
Investigators
Principal Investigator: Rodolfo Alejandro, M.D. Diabetes Research Institute, University of Miami

Publications:
Responsible Party: Camillo Ricordi and Jay Skyler, Professors, University of Miami Miller School of Medicine and Director/Deputy Director, Diabetes Research Institute, University of Miami
ClinicalTrials.gov Identifier: NCT02586831     History of Changes
Other Study ID Numbers: 20150856
First Posted: October 26, 2015    Key Record Dates
Last Update Posted: July 12, 2018
Last Verified: July 2018

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

Keywords provided by Camillo Ricordi and Jay Skyler, University of Miami:
Diabetes Mellitus, Type 1
Hypoglycemia
Autoimmune Diseases
Diabetes Mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Hypoglycemia
Diabetes Mellitus, Type 1
Autoimmune Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Immune System Diseases
Etanercept
Thymoglobulin
Antilymphocyte Serum
Interleukin-2
Lenograstim
Exenatide
Aldesleukin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors
Hypoglycemic Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists