~2 spots leftby Dec 2025

Incretin Hormones for Cystic Fibrosis

Recruiting in Palo Alto (17 mi)
Michael R. Rickels, MD, MS profile ...
Overseen byMichael Rickels, MD, MS
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Pennsylvania
Must not be taking: Corticosteroids
Disqualifiers: Non-CF diabetes, Pancreatitis, Transplant, others
No Placebo Group

Trial Summary

What is the purpose of this trial?

In recent years, diabetes has emerged as one of the most significant co-diseases that many Cystic Fibrosis (CF) patients develop. Type 1 (T1D) and Type 2 (T2D) diabetes results when either the body does not make enough insulin or the body does not respond correctly to this insulin, respectively. Insulin is a hormone which is made by cells in the pancreas and helps carry glucose (sugar) from the food we eat to the cells of the body for energy. While cystic fibrosis related diabetes (CFRD) has many features similar to both T1D and T2D, patients with CF may not have the same symptoms as either T1D or T2D patients. Currently, there is little understanding of CFRD and the best options for treatment remain unclear. The purpose of this research study is to examine and understand the various mechanisms that contribute to CFRD and gain a better understanding of potential means to treat CFRD. In particular, we plan to study the effects of incretin hormones that can enhance insulin production in CF patients. Enrollment is complete for the protocol as initially written. In order to further study the role of the incretin hormone on Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function , we have received approval to extend our investigation to include the following study groups: * Cystic Fibrosis participants with normal glucose tolerance * Non-Cystic Fibrosis controls

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, you should not have had any changes in therapy, including antibiotics, within 6 weeks prior to the study.

What data supports the effectiveness of the drug for cystic fibrosis?

Research shows that GLP-1, a component of the drug, can enhance insulin secretion in people with cystic fibrosis, suggesting potential benefits. Additionally, semaglutide, a GLP-1 receptor agonist, has been used to help control blood sugar in cystic fibrosis-related diabetes, indicating its effectiveness in managing glucose levels.12345

Is the treatment with incretin hormones like tirzepatide and semaglutide generally safe for humans?

Tirzepatide and semaglutide, which are incretin hormones, have been studied for type 2 diabetes and are generally considered safe, with common side effects including nausea, vomiting, diarrhea, and constipation, especially at higher doses. Cardiovascular safety has been evaluated, showing no increased risk of major cardiovascular events.46789

How is the drug for cystic fibrosis unique?

The drug uses incretin hormones, GLP-1 and GIP, which are gut hormones that help control blood sugar by increasing insulin and decreasing glucagon. This approach is novel for cystic fibrosis as it targets glucose control, which is often impaired in these patients, and GLP-1 has shown potential benefits in enhancing insulin secretion specifically in cystic fibrosis.1231011

Research Team

Michael R. Rickels, MD, MS profile ...

Michael Rickels, MD, MS

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults over 18 with cystic fibrosis and pancreatic insufficiency, who may have glucose tolerance issues but not severe diabetes. Women must test negative for pregnancy. Excluded are those with prior transplants, severe liver disease, abnormal kidney function, certain blood disorders or any condition that could interfere with the study.

Inclusion Criteria

I have been diagnosed with cystic fibrosis based on a sweat test or genetic testing.
My pancreas does not work properly.
My glucose tolerance test shows I have a form of diabetes related to cystic fibrosis without high blood sugar when fasting.
See 2 more

Exclusion Criteria

Medical co-morbidities that are not CF-related or are unstable per investigator opinion (i.e. history of bleeding disorders, immunodeficiency)
Hemoglobin less than10g/dL, within 90 days of Visit 1 or at Screening
Subjects, who in study team opinion, may be non-compliant with study procedures
See 16 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GLP-1 or GIP incretin hormone infusions and undergo GPA tests to measure insulin response

5 hours
1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • GIP (Hormone Therapy)
  • GLP-1 (Hormone Therapy)
Trial OverviewThe study investigates how incretin hormones (GLP-1 and GIP) affect insulin production in cystic fibrosis patients to better understand and treat CFRD. It includes CF patients with normal glucose levels and non-CF controls to compare responses.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: GLP-1 Incretin HormoneExperimental Treatment1 Intervention
The incretin, Glucagon-Like-peptide-1 (GLP-1) will be infused into the veins starting 30 minutes prior to initiating the GPA test. This infusion will continue for a total of 90 mins. (during the GPA for 230 mg/dL glucose levels) and then this will be stopped. The GPA test will be performed for the 340 mg/dL glucose levels but no incretin will be infused during this part of the test. These data will be compared when the subject repeats the GPA test with a placebo (saline or salt containing solution) infusion.
Group II: GIP Incretin HormoneExperimental Treatment1 Intervention
The incretin, Glucose-dependent Insulinotropic Polypeptide (GIP) will be infused into the veins starting 30 minutes prior to initiating the GPA test. This infusion will continue for a total of 90 mins (during the GPA for 230 mg/dL glucose levels) and then this will be stopped. The GPA test will be performed for the 340 mg/dL glucose levels but no incretin will be infused during this part of the test. These data will be compared when the subject repeats the GPA test with a placebo (saline or salt containing solution) infusion.

Find a Clinic Near You

Research Locations NearbySelect from list below to view details:
Children's Hospital of Philadelphia and University of PennsylvaniaPhiladelphia, PA
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Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials
2118
Patients Recruited
45,270,000+

Children's Hospital of Philadelphia

Collaborator

Trials
749
Patients Recruited
11,400,000+

Findings from Research

Effects of GLP-1 and GIP on Islet Function in Glucose-Intolerant, Pancreatic-Insufficient Cystic Fibrosis.Nyirjesy, SC., Peleckis, AJ., Eiel, JN., et al.[2023]
Effect of Sitagliptin on Islet Function in Pancreatic Insufficient Cystic Fibrosis With Abnormal Glucose Tolerance.Kelly, A., Sheikh, S., Stefanovski, D., et al.[2022]
Semaglutide in Cystic Fibrosis-Related Diabetes.Gnanapragasam, H., Mustafa, N., Bierbrauer, M., et al.[2022]
Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction.Nauck, MA., D'Alessio, DA.[2022]
Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus.Hillman, M., Eriksson, L., Mared, L., et al.[2012]
Tirzepatide: Clinical review of the "twincretin" injectable.Krauss, Z., Hintz, A., Fisk, R.[2023]
Tirzepatide, the Newest Medication for Type 2 Diabetes: A Review of the Literature and Implications for Clinical Practice.Bradley, CL., McMillin, SM., Hwang, AY., et al.[2023]
Recent Advances in Incretin-Based Pharmacotherapies for the Treatment of Obesity and Diabetes.Tan, Q., Akindehin, SE., Orsso, CE., et al.[2022]
Efficacy and safety of oral semaglutide in type 2 diabetes mellitus: A systematic review and meta-analysis.Li, A., Su, X., Hu, S., et al.[2023]
Role of a Dual Glucose-Dependent Insulinotropic Peptide (GIP)/Glucagon-like Peptide-1 Receptor Agonist (Twincretin) in Glycemic Control: From Pathophysiology to Treatment.Pelle, MC., Provenzano, M., Zaffina, I., et al.[2022]
Tirzepatide: A Dual Glucose-dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 Agonist for the Management of Type 2 Diabetes Mellitus.Wong, E., Cope, R., Dima, L., et al.[2023]

References

Effects of GLP-1 and GIP on Islet Function in Glucose-Intolerant, Pancreatic-Insufficient Cystic Fibrosis. [2023]
Effect of Sitagliptin on Islet Function in Pancreatic Insufficient Cystic Fibrosis With Abnormal Glucose Tolerance. [2022]
Semaglutide in Cystic Fibrosis-Related Diabetes. [2022]
Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. [2022]
Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus. [2012]
Tirzepatide: Clinical review of the "twincretin" injectable. [2023]
Tirzepatide, the Newest Medication for Type 2 Diabetes: A Review of the Literature and Implications for Clinical Practice. [2023]
Recent Advances in Incretin-Based Pharmacotherapies for the Treatment of Obesity and Diabetes. [2022]
Efficacy and safety of oral semaglutide in type 2 diabetes mellitus: A systematic review and meta-analysis. [2023]
Role of a Dual Glucose-Dependent Insulinotropic Peptide (GIP)/Glucagon-like Peptide-1 Receptor Agonist (Twincretin) in Glycemic Control: From Pathophysiology to Treatment. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Tirzepatide: A Dual Glucose-dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 Agonist for the Management of Type 2 Diabetes Mellitus. [2023]