GLP-1 Agonist Therapy for Cystic Fibrosis-related Diabetes

Recruiting in Palo Alto (17 mi)

Overseen by Michael Rickels, MD, MS

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Pennsylvania

Must be taking: GLP-1 agonists

Disqualifiers: Low BMI, Heart defects, Pregnancy, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Diabetes is a major co-morbidity in pancreatic insufficient cystic fibrosis (PI-CF) and associated with worse outcomes. While reduced β-cell mass contributes to the insulin secretory defects that characterizes cystic fibrosis-related diabetes (CFRD), other modifiable determinants appear operative in the emergence and progression of abnormal glucose tolerance towards diabetes. Identifying interventions to preserve β-cell function are crucial for delaying and potentially preventing CFRD development. In this study, we hypothesize that weekly administration of the long-acting glucagon-like peptide-1 (GLP-1) agonist dulaglutide will improve defective early-phase insulin secretion and improve glucose tolerance during a mixed-meal tolerance test.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using prandial insulin or repaglinide for diabetes, you may continue these medications during the study.

What data supports the effectiveness of the drug Dulaglutide (Trulicity) for treating cystic fibrosis-related diabetes?

Dulaglutide (Trulicity) is effective in lowering blood sugar levels in people with type 2 diabetes, and it also helps with weight reduction and reducing the risk of major heart problems. While this data is specific to type 2 diabetes, it suggests potential benefits for managing blood sugar in other conditions like cystic fibrosis-related diabetes. ^{1 2 3 4 5}

Is dulaglutide (Trulicity) safe for humans?

Dulaglutide (Trulicity) is generally well tolerated in humans, with the most common side effects being related to the stomach and intestines, like nausea. It has been used safely in people with type 2 diabetes, including those with other health issues like heart disease and kidney problems. ^{1 2 3 4 5}

How is the drug Dulaglutide unique for treating cystic fibrosis-related diabetes?

Dulaglutide is unique because it is a once-weekly injection that mimics a natural hormone (GLP-1) to help control blood sugar levels, which is different from other diabetes treatments that often require daily dosing. ^{1 2 3 4 5}

Research Team

Michael Rickels, MD, MS

Principal Investigator

University of Pennsylvania

Andrea Kelly, M.D, M.S.

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

Adults aged 18+ with cystic fibrosis, pancreatic insufficiency requiring enzyme replacement, and abnormal glucose tolerance but not full-blown diabetes can join. They must be able to take weekly subcutaneous medication and follow the study's procedures. Women should use effective contraception.

Inclusion Criteria

Abnormal glucose tolerance defined by OGTT criteria for EGI, IGT, or CFRD, or diagnosed CFRD

I am 18 years old or older.

I have been diagnosed with Cystic Fibrosis based on a sweat test or genetic test.

Exclusion Criteria

I have diabetes (not CF related) or CFRD with high fasting blood sugar.

I or my family have a history of medullary thyroid cancer or MEN2.

History of any illness or condition that, in the opinion of the investigator might confound the results of the study or pose an additional risk to the subject

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observation

Participants undergo a Mixed Meal Tolerance Test at baseline and after 6 weeks of no intervention

6 weeks

2 visits (in-person)

Treatment

Participants receive weekly administration of dulaglutide and undergo a Mixed Meal Tolerance Test at baseline and after 6 weeks

6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dulaglutide (GLP-1 Agonist)

Trial Overview The trial is testing if a weekly shot of Dulaglutide, a GLP-1 agonist, can help improve insulin secretion and glucose tolerance in people with cystic fibrosis who have issues with blood sugar levels.

Participant Groups

Group I: Dulaglutide Experimental Treatment 1 Intervention

The Mixed Meal Tolerance Test as described in the primary outcome section will be performed at baseline and after 6 weeks of dulaglutide therapy in the intervention period.

Group II: Observation Active Control 1 Intervention

The Mixed Meal Tolerance Test as described in the primary outcome section will be performed at baseline and after 6 weeks of no intervention in the observation period.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Dr. Joan Lau

University of Pennsylvania

Chief Executive Officer since 2020

PhD in Neuroscience from the University of Cincinnati College of Medicine, MBA from the Wharton School of Business, BS in Bioengineering from the University of Pennsylvania

Dr. Robert Iannone

University of Pennsylvania

Chief Medical Officer since 2019

MD from Yale University, MSCE from the University of Pennsylvania

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Joseph W. St. Geme III

Children's Hospital of Philadelphia

Chief Medical Officer since 2021

MD, PhD, MPH

Madeline Bell

Children's Hospital of Philadelphia

Chief Executive Officer since 2015

BSc in Nursing from Villanova University, MSc in Organizational Dynamics from the University of Pennsylvania

Findings from Research

Dulaglutide (Trulicity) is a once-weekly GLP-1 agonist that has been approved for the treatment of type 2 diabetes, providing a convenient dosing schedule for patients.

As the third GLP-1 agonist available, dulaglutide offers an effective option for managing blood sugar levels in individuals with type 2 diabetes, contributing to improved glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dulaglutide (Trulicity): The Third Once-Weekly GLP-1 Agonist. Smith, LL., Mosley, JF., Parke, C., et al.[2020]

Dulaglutide, a GLP-1 receptor agonist, has shown superior efficacy in lowering blood sugar levels compared to placebo and other diabetes medications, making it a strong option for treating type 2 diabetes.

The drug is administered once a week, has a favorable safety profile with common gastrointestinal side effects, and offers patient satisfaction similar to other GLP-1 receptor agonists, while also promoting weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the treatment of type 2 diabetes: impact of dulaglutide. Thompson, AM., Trujillo, JM.[2020]

Dulaglutide (Trulicity™) is a long-acting GLP-1 receptor agonist specifically designed for treating type 2 diabetes, demonstrating a novel mechanism of action by mimicking the effects of the GLP-1 hormone.

The drug has received approval for subcutaneous use in the US and is recommended for approval in the EU, indicating its efficacy and safety profile in managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dulaglutide: first global approval. Sanford, M.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Dulaglutide (Trulicity): The Third Once-Weekly GLP-1 Agonist. [2020]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Advances in the treatment of type 2 diabetes: impact of dulaglutide. [2020]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Dulaglutide: first global approval. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Dulaglutide: A Review in Type 2 Diabetes. [2021]

5. Belgium pubmed.ncbi.nlm.nih.gov

[Dulaglutide (Trulicity®), a new once-weekly agonist of glucagon-like peptide-1 receptors for type 2 diabetes]. [2016]