Targeting Beta Cell Dysfunction With Liraglutide or Golimumab in Longstanding T1D

Targeting Beta Cell Dysfunction in Longstanding T1D

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Liraglutide; Drug: Golimumab

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Diabetes and Osteoporosis Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Benaroya Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liraglutide; Participants will receive subcutaneous (SC) liraglutide for 8 weeks	Drug: Liraglutide; Participants will receive subcutaneous (SC) liraglutide for 8 weeks; Other Names: Victoza
Experimental: Golimumab; Participants will receive subcutaneous (SC) golimumab for 8 weeks	Drug: Golimumab; Participants will receive subcutaneous (SC) golimumab for 8 weeks; Other Names: SIMPONI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of individuals with peak MMTT stimulated C-peptide >0.017 pmol/mL.	0-to-8 weeks

Collaborators and Investigators

• Sponsor: Carla Greenbaum, MD
• Collaborators: Juvenile Diabetes Research Foundation
• Investigators: Principal Investigator: Carla Greenbaum, MD, Benaroya Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2018
• Primary Completion (Actual): November 9, 2021
• Study Completion (Actual): November 9, 2021

Study Registration Dates

• First Submitted: August 13, 2018
• First Submitted That Met QC Criteria: August 13, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 21, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tumor Necrosis Factor Inhibitors; Liraglutide; Golimumab
• Other Study ID Numbers: IRB18-044

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No