Clinical trial NCT03632759: Targeting Beta Cell Dysfunction With Liraglutide or Golimumab in Longstanding T1D
Official title: Targeting Beta Cell Dysfunction in Longstanding T1D
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Benaroya Research Institute
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2018-08-15
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: two independent open label, proof of concept studies
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Proportion of individuals with peak MMTT stimulated C-peptide >0.017 pmol/mL.
timeFrame: 0-to-8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes and Osteoporosis Center
state: Idaho
city: Seattle
country: United States
facility: Benaroya Research Institute
state: Washington
Study officials:
affiliation: Benaroya Research Institute
name: Carla Greenbaum, MD
role: PRINCIPAL_INVESTIGATOR
References: