PMID- 25500887
OWN - NLM
STAT- MEDLINE
DCOM- 20150421
LR  - 20221207
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 125
IP  - 1
DP  - 2015 Jan
TI  - Anti-thymocyte globulin/G-CSF treatment preserves beta cell function in patients 
      with established type 1 diabetes.
PG  - 448-55
LID - 78492 [pii]
LID - 10.1172/JCI78492 [doi]
AB  - BACKGROUND: Previous efforts to preserve beta cell function in individuals with type 
      1 diabetes (T1D) have focused largely on the use of single immunomodulatory 
      agents administered within 100 days of diagnosis. Based on human and preclinical 
      studies, we hypothesized that a combination of low-dose anti-thymocyte globulin 
      (ATG) and pegylated granulocyte CSF (G-CSF) would preserve beta cell function in 
      patients with established T1D (duration of T1D >4 months and <2 years). METHODS: 
      A randomized, single-blinded, placebo-controlled trial was performed on 25 
      subjects: 17 subjects received ATG (2.5 mg/kg intravenously) followed by 
      pegylated G-CSF (6 mg subcutaneously every 2 weeks for 6 doses) and 8 subjects 
      received placebo. The primary outcome was the 1-year change in AUC C-peptide 
      following a 2-hour mixed-meal tolerance test (MMTT). At baseline, the age (mean +/- 
      SD) was 24.6 +/- 10 years; mean BMI was 25.4 +/- 5.2 kg/m(2); mean A1c was 6.5% +/- 1.1%; 
      insulin use was 0.31 +/- 0.22 units/kg/d; and length of diagnosis was 1 +/- 0.5 
      years. RESULTS: Combination ATG/G-CSF treatment tended to preserve beta cell 
      function in patients with established T1D. The mean difference in MMTT-stimulated 
      AUC C-peptide between treated and placebo subjects was 0.28 nmol/l/min (95% CI 
      0.001-0.552, P = 0.050). A1c was lower in ATG/G-CSF-treated subjects at the 
      6-month study visit. ATG/G-CSF therapy was associated with relative preservation 
      of Tregs. CONCLUSIONS: Patients with established T1D may benefit from combination 
      immunotherapy approaches to preserve beta cell function. Further studies are needed 
      to determine whether such approaches may prevent or delay the onset of the 
      disease. TRIAL REGISTRATION: Clinicaltrials.gov NCT01106157. FUNDING: The Leona 
      M. and Harry B. Helmsley Charitable Trust and Sanofi.
FAU - Haller, Michael J
AU  - Haller MJ
FAU - Gitelman, Stephen E
AU  - Gitelman SE
FAU - Gottlieb, Peter A
AU  - Gottlieb PA
FAU - Michels, Aaron W
AU  - Michels AW
FAU - Rosenthal, Stephen M
AU  - Rosenthal SM
FAU - Shuster, Jonathan J
AU  - Shuster JJ
FAU - Zou, Baiming
AU  - Zou B
FAU - Brusko, Todd M
AU  - Brusko TM
FAU - Hulme, Maigan A
AU  - Hulme MA
FAU - Wasserfall, Clive H
AU  - Wasserfall CH
FAU - Mathews, Clayton E
AU  - Mathews CE
FAU - Atkinson, Mark A
AU  - Atkinson MA
FAU - Schatz, Desmond A
AU  - Schatz DA
LA  - eng
SI  - ClinicalTrials.gov/NCT01106157
GR  - P01 AI042288/AI/NIAID NIH HHS/United States
GR  - P30 DK063720/DK/NIDDK NIH HHS/United States
GR  - UL1TR001082/TR/NCATS NIH HHS/United States
GR  - 1UL1TR000064/TR/NCATS NIH HHS/United States
GR  - UL1 TR000064/TR/NCATS NIH HHS/United States
GR  - UL1 TR001427/TR/NCATS NIH HHS/United States
GR  - UL1TR000004/TR/NCATS NIH HHS/United States
GR  - UL1 TR001082/TR/NCATS NIH HHS/United States
GR  - UL1 TR000004/TR/NCATS NIH HHS/United States
GR  - P01-AI42288/AI/NIAID NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141215
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Antilymphocyte Serum)
RN  - 0 (C-Peptide)
RN  - 0 (Drug Combinations)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 0 (pegylated granulocyte colony-stimulating factor, human)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
SB  - IM
CIN - J Clin Invest. 2015 Jan;125(1):94-6. PMID: 25500880
MH  - Adolescent
MH  - Adult
MH  - Antilymphocyte Serum/*therapeutic use
MH  - C-Peptide/blood
MH  - Child
MH  - Diabetes Mellitus, Type 1/blood/*drug therapy
MH  - Drug Combinations
MH  - Female
MH  - Glycated Hemoglobin/metabolism
MH  - Granulocyte Colony-Stimulating Factor/*therapeutic use
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Insulin/therapeutic use
MH  - Insulin-Secreting Cells/*physiology
MH  - Male
MH  - Middle Aged
MH  - Polyethylene Glycols/*therapeutic use
MH  - Single-Blind Method
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC4382237
EDAT- 2014/12/17 06:00
MHDA- 2015/04/22 06:00
PMCR- 2015/04/02
CRDT- 2014/12/16 06:00
PHST- 2014/08/20 00:00 [received]
PHST- 2014/10/31 00:00 [accepted]
PHST- 2014/12/16 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/04/22 06:00 [medline]
PHST- 2015/04/02 00:00 [pmc-release]
AID - 78492 [pii]
AID - 10.1172/JCI78492 [doi]
PST - ppublish
SO  - J Clin Invest. 2015 Jan;125(1):448-55. doi: 10.1172/JCI78492. Epub 2014 Dec 15.