Targeting Beta Cell Dysfunction With Liraglutide or Golimumab in Longstanding T1D

NCT ID: NCT03632759

Last Updated: 2022-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-15
• Study Completion Date: 2021-11-09

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.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Liraglutide

Participants will receive subcutaneous (SC) liraglutide for 8 weeks

Group Type: EXPERIMENTAL

Liraglutide

Intervention Type: DRUG

Participants will receive subcutaneous (SC) liraglutide for 8 weeks

Golimumab

Participants will receive subcutaneous (SC) golimumab for 8 weeks

Group Type: EXPERIMENTAL

Golimumab

Intervention Type: DRUG

Participants will receive subcutaneous (SC) golimumab for 8 weeks

Interventions

Liraglutide

Participants will receive subcutaneous (SC) liraglutide for 8 weeks

Intervention Type: DRUG

Golimumab

Participants will receive subcutaneous (SC) golimumab for 8 weeks

Intervention Type: DRUG

Other Intervention Names

Victoza; SIMPONI

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

Carla Greenbaum, MD

OTHER

Sponsor Role: lead

Responsible Party

Carla Greenbaum, MD

Director, Diabetes Program

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Carla Greenbaum, MD

Role: PRINCIPAL_INVESTIGATOR

Benaroya Research Institute

Locations

Rocky Mountain Diabetes and Osteoporosis Center

Idaho Falls, Idaho, United States

Benaroya Research Institute

Seattle, Washington, United States

Countries

United States

References

Lord SM, Bahnson HT, Greenbaum CJ, Liljenquist DR, Virostko J, Speake C. Testing a new platform to screen disease-modifying therapy in type 1 diabetes. PLoS One. 2023 Dec 14;18(12):e0293268. doi: 10.1371/journal.pone.0293268. eCollection 2023.

Reference Type: DERIVED

PMID: 38096190 (View on PubMed)

Other Identifiers

IRB18-044

Identifier Type: -

Identifier Source: org_study_id