Effect of Chronic Incretin-based Therapy in Cystic Fibrosis

NCT ID: NCT01879228

Last Updated: 2022-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2020-03-31

Brief Summary

In recent years, diabetes has emerged as one of the most significant co-diseases that many Cystic Fibrosis (CF) patients develop. Type 1 and Type 2 diabetes results when either the body does not make enough insulin or the body does not respond correctly to this insulin. 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 Type 1 and Type 2 diabetes, it is very different; therefore, treatment and care of CFRD is not the same.

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. The primary objective is to determine effectiveness of chronic incretin-based therapy vs. placebo on insulin secretion in CF patients with indeterminate glucose tolerance, impaired glucose tolerance, or CFRD.

Detailed Description

Insufficient incretin action has been associated with T2D. To study the possible link between insufficient incretin action and impaired insulin secretion in CFRD as in T2D, the present study will determine whether early intervention with incretin-based therapy using the DPP-4 inhibitor sitagliptin (Januvia®) to raise endogenous levels of the incretin hormones--i.e.--glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) for a 6-month period will improve insulin secretion in CF patients with indeterminate glucose tolerance, impaired glucose tolerance or early CFRD.

Conditions

Cystic Fibrosis; Pancreatic Insufficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Sitagliptin

The dose of sitagliptin (Januvia®) 100 mg tablet will be taken orally each morning for 6 months.

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

The GPA test as described in the primary outcome section will be performed at baseline and after 6 months of therapy in the Sitagliptin and placebo arms. Furthermore, evaluation of endogenous GLP-1 levels will be assessed by a mixed meal tolerance test compared at baseline and 6 months.

Placebo

Placebo tablet will be taken orally each morning for 6 months.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The GPA test as described in the primary outcome section will be performed at baseline and after 6 months of therapy in the Sitagliptin and placebo arms. Furthermore, evaluation of endogenous GLP-1 levels will be assessed by a mixed meal tolerance test compared at baseline and 6 months.

Interventions

Sitagliptin

The GPA test as described in the primary outcome section will be performed at baseline and after 6 months of therapy in the Sitagliptin and placebo arms. Furthermore, evaluation of endogenous GLP-1 levels will be assessed by a mixed meal tolerance test compared at baseline and 6 months.

Intervention Type: DRUG

Placebo

The GPA test as described in the primary outcome section will be performed at baseline and after 6 months of therapy in the Sitagliptin and placebo arms. Furthermore, evaluation of endogenous GLP-1 levels will be assessed by a mixed meal tolerance test compared at baseline and 6 months.

Intervention Type: DRUG

Other Intervention Names

Januvia

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of CF, defined by positive sweat test or CFTR mutation analysis according to CFF diagnostic criteria
• Age ≥ 18y on date of consent
• Pancreatic insufficiency
• Recent OGTT consistent with Indeterminate-GT, IGT, CFRD w/o fasting hyperglycemia, or an established diagnosis of CFRD without fasting hyperglycemia
• For female subjects, negative urine pregnancy test at enrollment.

Exclusion Criteria

• Established diagnosis of non-CF diabetes (i.e. T1D) or CFRD with fasting hyperglycemia, (fasting glucose > 126 mg/dL)
• History of clinically symptomatic pancreatitis within last year,
• Prior lung or liver transplant,
• Severe CF liver disease, as defined by portal hypertension,
• Fundoplication-related dumping syndrome,
• Medical co-morbidities that are not CF-related or are unstable per investigator opinion (i.e. history of bleeding disorders, immunodeficiency),
• Acute illness or changes in therapy (including antibiotics) within 6 weeks prior to enrollment,
• Treatment with oral or intravenous corticosteroids within 6 weeks of enrollment,
• Hemoglobin <10g/dL, within 90 days of Visit 1 or at Screening,
• Abnormal renal function, within 90 days of Visit 1 or at Screening; defined as Creatinine clearance < 50 mL/min (based on the Cockcroft-Gault formula) or potassium > 5.5mEq/L on non-hemolyzed specimen,
• A history of anaphylaxis, angioedema or Stevens-Johnson syndrome,
• Inability to perform study specific procedures (MMTT, GPA),
• Subjects, who in study team opinion, may be non-compliant with study procedures.

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

Sponsors

Children's Hospital of Philadelphia

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Michael R. Rickels, MD, MS

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael M Rickels, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Children's Hospital of Philadelphia and University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

Kelly A, Sheikh S, Stefanovski D, Peleckis AJ, Nyirjesy SC, Eiel JN, Sidhaye A, Localio R, Gallop R, De Leon DD, Hadjiliadis D, Rubenstein RC, Rickels MR. Effect of Sitagliptin on Islet Function in Pancreatic Insufficient Cystic Fibrosis With Abnormal Glucose Tolerance. J Clin Endocrinol Metab. 2021 Aug 18;106(9):2617-2634. doi: 10.1210/clinem/dgab365. Epub 2021 May 22.

Reference Type: DERIVED

PMID: 34406395 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/34406395/

Published paper for this study titled: "Effect of Sitagliptin on Islet Function in Pancreatic Insufficient Cystic Fibrosis With Abnormal Glucose Tolerance".

Other Identifiers

818014

Identifier Type: -

Identifier Source: org_study_id