Targeting Beta Cell Dysfunction With Liraglutide or Golimumab in Longstanding T1D

• Sponsor: Carla Greenbaum, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT03632759
• Collaborator: Juvenile Diabetes Research Foundation (Other)
• Enrollment: 16
• Locations: 2
• Arms: 2
• Actual Duration (Months): 38.8
• Patients Per Site: 8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Mellitus	Drug: Liraglutide; Drug: Golimumab	Early Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: two independent open label, proof of concept studiestwo independent open label, proof of concept studies
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Targeting Beta Cell Dysfunction in Longstanding T1D
• Actual Study Start Date: Aug 15, 2018
• Actual Primary Completion Date: Nov 9, 2021
• Actual Study Completion Date: Nov 9, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Proportion of individuals with peak MMTT stimulated C-peptide >0.017 pmol/mL. [0-to-8 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts 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)

10. Any history of pancreatitis or elevated amylase or lipase.

11. Any personal or family history of thyroid C-cell tumors, including medullary thyroid carcinoma (MTC).

12. Any personal or family history of multiple endocrine neoplasia syndrome type 2.

13. Hypersensitivity to liraglutide.

14. Previous treatment with liraglutide.

15. Known history of clinically significant gastroparesis.

16. For Study B (golimumab)

17. Any history of recent (within 3 months) serious bacterial, viral, fungal, or other opportunistic infections.

18. Any history of demyelinating diseases (such as multiple sclerosis), heart failure, or left ventricular dysfunction.

19. Serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C.

20. Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection.

21. Active infection with EBV, defined by real-time PCR.

22. Active infection with CMV, defined by real-time PCR.

23. 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

1. Receipt of live vaccine (in the 6 weeks before treatment)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rocky Mountain Diabetes and Osteoporosis Center	Idaho Falls	Idaho	United States	83404
2	Benaroya Research Institute	Seattle	Washington	United States	98101

Sponsors and Collaborators

• Carla Greenbaum, MD
• Juvenile Diabetes Research Foundation

Investigators

• Principal Investigator: Carla Greenbaum, MD, Benaroya Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Carla Greenbaum, MD, Director, Diabetes Program, Benaroya Research Institute
• ClinicalTrials.gov Identifier: NCT03632759
• Other Study ID Numbers: IRB18-044
• First Posted: Aug 15, 2018
• Last Update Posted: Jan 24, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• 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
• Additional relevant MeSH terms: Diabetes Mellitus, Type 1; Liraglutide; Golimumab

Study Results

No Results Posted as of Jan 24, 2022