Type 1 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to determine whether 8 weeks of Liraglutide or Golimumab can transiently improve beta cell function in patients with longstanding Type 1 diabetes (T1D) who secrete proinsulin and little/no C-peptide.
Interventions
DRUGLiraglutide
Participants will receive subcutaneous (SC) liraglutide for 8 weeks
DRUGGolimumab
Participants will receive subcutaneous (SC) golimumab for 8 weeks
Sponsors
Juvenile Diabetes Research Foundation
Carla Greenbaum, MD
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
two independent open label, proof of concept studies
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. ≥ 3 years from Type 1 diabetes diagnosis 2. Males and females 18-50 years of age, inclusive 3. Peak MMTT stimulated C-peptide \<0.017 pmol/mL 4. Proinsulin levels ≥ 2 pM (either fasting or stimulated) 5. Females of child-bearing potential must be willing to use effective birth control for 12 weeks 6. Willing and able to give informed consent for participation 7. HbA1c ≤ 8.5%
Exclusion criteria
1. Concurrent use of non-insulin therapies aimed to control hyperglycemia or use within the past 30 days of screening MMTT (V-2). 2. History of severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies. 3. Diagnosis of liver disease or elevated hepatic enzymes, as defined by ALT or AST\> 1.5 x the upper limit of age-determined normal (ULN) . 4. Females who are pregnant or lactating. 5. Receipt of an immune modulating biologic or investigational drug within 3 months or 5 half-lives before enrollment. 6. History of other clinically significant autoimmune disease needing chronic therapy with biologics or steroids with the exception of celiac and stable thyroid disease. 7. Current use of any medication known to significantly influence glucose tolerance (e.g. oral steroids, atypical antipsychotics, diphenylhydantoin, niacin). 8. Any medical or psychological condition that in the opinion of the principal investigator would interfere with the safe completion of the trial. 9. For Study A (liraglutide) 1. Any history of pancreatitis or elevated amylase or lipase. 2. Any personal or family history of thyroid C-cell tumors, including medullary thyroid carcinoma (MTC). 3. Any personal or family history of multiple endocrine neoplasia syndrome type 2. 4. Hypersensitivity to liraglutide. 5. Previous treatment with liraglutide. 6. Known history of clinically significant gastroparesis. 10. For Study B (golimumab) 1. Any history of recent (within 3 months) serious bacterial, viral, fungal, or other opportunistic infections. 2. Any history of demyelinating diseases (such as multiple sclerosis), heart failure, or left ventricular dysfunction. 3. Serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C. 4. Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection. 5. Active infection with EBV, defined by real-time PCR. 6. Active infection with CMV, defined by real-time PCR. 7. Any of the following hematologic abnormalities at screening: * White blood count \<3,000/μL or \>14,000/μL * Lymphocyte count \<500/μL * Platelet count \<140,000 /μL * Hemoglobin \<8.5 g/dL * Neutrophil count \<2,000 cells/μL 8. Receipt of live vaccine (in the 6 weeks before treatment)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of individuals with peak MMTT stimulated C-peptide >0.017 pmol/mL. | 0-to-8 weeks |
Countries
United States
Outcome results
None listed