Reversing Type 1 Diabetes After it is Established - Full Text View

Sponsor:	University of Florida
Collaborators:	The Helmsley Charitable Trust Genzyme
Information provided by (Responsible Party):	University of Florida
ClinicalTrials.gov Identifier:	NCT01106157

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:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Type 1

Drug Information available for: Granulocyte colony-stimulating factor Pegfilgrastim Antilymphocyte Serum

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 comparision 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:	September 2014
Estimated Primary Completion Date:	July 2013 (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
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

Contacts

Contact: Mary A. Dennis, MSN, RN	352.273.9265	madennis@peds.ufl.edu
Contact: Michael J. Haller, MD	352.273.9264	hallemj@peds.ufl.edu

Locations

United States, California
University of California, San Francisco	Recruiting
San Francisco, California, United States, 94143-0748
Contact: Kathleen Fraser 415-353-9084 kfraser@diabetes.ucsf.edu
Contact: Stephen E. Gitelman, MD 415.476.3748 sgitelman@peds.ucsfl.edu
Principal Investigator: Stephen E. Gitelman, MD
United States, Colorado
Barbara Davis Center for Childhood Diabetes	Recruiting
Aurora, Colorado, United States, 80045-6511
Contact: Lisa Myers 303-724-6893 Lisa.Myers@ucdenver.edu
Contact: Jenna Lungaro, BS 303.724.6758 Jenna.Lungaro@ucdenver.edu
Principal Investigator: Peter Gottlieb, MD, PhD
Sub-Investigator: Aaron Michels, MD
United States, Florida
University of Florida	Recruiting
Gainesville, Florida, United States, 32610-0296
Contact: Michael J. Haller, MD 352-273-9264 hallemj@peds.ufl.edu
Contact: Mary A. Dennis, MSN, RN 352.273.9265 madennis@peds.ufl.edu
Principal Investigator: Michael J. Haller, MD
Sub-Investigator: Desmond A. Schatz, MD

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:

Parker MJ, Xue S, Alexander JJ, Wasserfall CH, Campbell-Thompson ML, Battaglia M, Gregori S, Mathews CE, Song S, Troutt M, Eisenbeis S, Williams J, Schatz DA, Haller MJ, Atkinson MA. Immune depletion with cellular mobilization imparts immunoregulation and reverses autoimmune diabetes in nonobese diabetic mice. Diabetes. 2009 Oct;58(10):2277-84. Epub 2009 Jul 23.

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:	February 29, 2012
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 24, 2012