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Reversing Type 1 Diabetes After it is Established

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
The Helmsley Charitable Trust
Genzyme
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01106157
First received: April 15, 2010
Last updated: May 10, 2013
Last verified: April 2013
History of Changes
  Purpose

The primary purpose of this study is to determine if giving the combination therapy consisting of Thymoglobulin® (ATG) and Neulasta® (GCSF) to patients with established Type 1 Diabetes (T1D) is safe and secondarily, if the ATG and GCSF will preserve insulin production.


Condition Intervention Phase
Diabetes Mellitus, Type 1
 Drug: Anti-Thymocyte Globin plus pegylated GCSF
Drug: Placebo
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Reversing Type 1 Diabetes After it is Established: A Pilot Safety and Feasibility Study of Anti-Thymocyte Globulin (Thymoglobulin®)and Pegylated GCSF (Neulasta®) in Established Type 1 Diabetes

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Metabolic Function [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Longitudinal comparison of blood glucose control, insulin usage, c-peptide production


Secondary Outcome Measures:
  • Immune Responsiveness [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Mechanistic understanding of potential of ATG + GCSF to modulate immune reactivities and induce tolerance in an autoimmune setting, with a focus on the role for T (Treg) cells


Estimated Enrollment: 25
Study Start Date: April 2010
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ATG + GCSF
Subjects will receive an infusion of ATG followed by 6 doses of GCSF every 2 weeks for 10 weeks.
 Drug: Anti-Thymocyte Globin plus pegylated GCSF
Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion
Other Names:
  • Anti-Thymocyte Globin (Thymoglobulin)
  • Pegylated GCSF (Neulasta)
Placebo Comparator: Placebo
Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner
 Drug: Placebo
Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes

Detailed Description:

This is a randomized, placebo controlled, phase I/II trial. Potential subjects will be screened via a 4 hour mixed meal tolerance test to assess residual beta cell (C-peptide) function. If the C-peptide level at any time is ≥ 0.1 pmol/ml, and the subject meets the additional inclusion and exclusion criteria, they will be eligible for randomization and enrollment. The study will be randomized 2:1 such that 17 subjects will receive active therapy and 8 will receive placebo. Subjects must receive Thymoglobulin®/ Neulasta® or placebo within 8 weeks of randomization. Thymoglobulin® (2.5mg/kg)/placebo will be given as 0.5 mg/kg IV on day 1 and 2 mg/kg on day 2. Six doses of Neulasta® (6mg/dose)/placebo will be given SC every 2 weeks, with the first dose given prior to discharge after the Thymoglobulin® infusion. Complete metabolic panel (CMP) and CBC will be done at the screening visit, just prior to study drug initiation, daily during the Thymoglobulin® infusion admission, and at follow up visits. Following discharge, daily phone calls will be made to the subjects during the first 5 days of therapy and weekly thereafter. In addition, weekly phone calls for the month following completion of therapy will be used to document adverse reactions. Thereafter calls will be made every two weeks.

  Eligibility

Ages Eligible for Study:   12 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must be > 12 years < 45
  • Must have a diagnosis of T1D of greater than 4 months duration, with an upper limit of 2 years, Now only recruiting for those diagnosed greater than 1 year but less than 2 years.
  • Must have at least one diabetes-related autoantibody present (e.g., ICA, GAD, ZnT8, or IA2 autoantibodies)
  • Must have stimulated C-peptide levels ≥ 0.1 pmol/ml (0.3ng/mL) when measured during a mixed meal tolerance test (MMTT), conducted at least 4 months from diagnosis of diabetes, and within 8 weeks of randomization
  • Must be EBV PCR negative within two weeks of randomization if EBV seronegative at screening
  • Be at least 6 weeks from last live immunization
  • Be willing to forgo live vaccines for 3 months following last dose of study drug
  • Be willing to comply with intensive diabetes management
  • Normal screening values for CBC, renal function and electrolytes (CMP).

Exclusion Criteria:

  • Be immunodeficient or have clinically significant chronic lymphopenia: (Leukopenia (< 3,000 leukocytes /μL), neutropenia (<1,500 neutrophils/μL), lymphopenia (<800 lymphocytes/μL), or thrombocytopenia (<125,000 platelets/μL).
  • Have a chronic infection at time of randomization
  • Have a positive PPD
  • Be currently pregnant or lactating, or anticipate getting pregnant within the next two years
  • Require use of other immunosuppressive agents
  • Have serologic evidence of current or past HIV, Tuberculosis, Hepatitis B or Hepatitis C infection
  • Have any complicating medical issues or abnormal clinical laboratory results that interfere with study conduct, or cause increased risk to include pre-existing cardiac disease, COPD, sickle cell disease, neurological, or blood count abnormalities (e.g., lymphopenia, leukopenia, or thrombocytopenia)
  • Have a history of malignancies
  • Evidence of liver dysfunction with AST or ALT greater than 3 times the upper limits of normal
  • Evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal
  • Vaccination with a live virus within the last 6 weeks
  • Current use of non-insulin pharmaceuticals that affect glycemic control
  • Active participation in another T1D treatment study in the previous 30 days
  • Known allergy to G-CSF or ATG
  • Prior treatment with ATG or known allergy to rabbit derived products
  • Any condition that in the investigator's opinion, may adversely affect study participation or may compromise the study results
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01106157

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143-0748
United States, Colorado
Barbara Davis Center for Childhood Diabetes
Aurora, Colorado, United States, 80045-6511
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610-0296
Sponsors and Collaborators
University of Florida
The Helmsley Charitable Trust
Genzyme
Investigators
Principal Investigator: Michael J. Haller, MD University of Florida Pediatric Endocrinology
  More Information

Additional Information:
UF Diabetes Center of Excellence  This link exits the ClinicalTrials.gov site
UF ATG-GCSF Study Description  This link exits the ClinicalTrials.gov site
UCSF Diabetes Center  This link exits the ClinicalTrials.gov site

Publications:

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01106157     History of Changes
Other Study ID Numbers: UF-ATG-GCSF001
Study First Received: April 15, 2010
Last Updated: May 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
Autoimmune, Diabetes Mellitus, Glucose Metabolism

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
 Antilymphocyte Serum
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on May 23, 2013