Effect of Chronic Incretin-based Therapy in Cystic Fibrosis

NCT01879228 | Completed Results DMC

• 1 other identifier: 818014
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis; Pancreatic Insufficiency

Keywords

Cystic Fibrosis; Diabetes; Pancreatic Insufficiency

Outcome Measures

Primary Outcomes (1)

• Change in Second-phase Insulin Response Derived From the Glucose-potentiated Arginine Test as a Measure of β-cell Sensitivity to Glucose at Baseline and at 6 Months

  The key endpoint of interest will be the change in second phase insulin response derived from the Glucose-Potentiated Arginine (GPA) test. The GPA test will measure insulin, which will be a measure of pancreatic endocrine function in response to the injection of arginine. Arginine is a naturally occurring amino acid (substance) in the body. It will be given in the veins to make the pancreas secrete insulin. After the first injection of arginine, a glucose infusion will be started in order to raise the level of sugar in the blood to 230 mg/dl. Once the level is achieved, arginine will be injected again and blood samples are measured. After a 2 hour break, the glucose infusion will be started to achieve a blood sugar of 340 mg/dl and the arginine injection will be repeated. Comparison of responses at baseline and after 6 months of incretin-based therapy (Sitagliptin) or placebo will be performed using statistical methods.

  Baseline and 6 months

Study Arms (2)

Sitagliptin

EXPERIMENTAL

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

Drug: Sitagliptin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Sitagliptin 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.

Also known as: Januvia

Sitagliptin

Placebo 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Children's Hospital of Philadelphia: collaborator

Study Sites (1)

Children's Hospital of Philadelphia and University of Pennsylvania

Philadelphia, Pennsylvania, 19194, United States

Location

Related Publications (1)

• 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.

  PMID: 34406395 DERIVED

Related Links

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

MeSH Terms

Conditions

Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Diabetes Mellitus

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Paola Alvarado
• Organization: University of Pennsylvannia

paola.alvarado@pennmedicine.upenn.edu

215-746-2081

Study Officials

• Michael M Rickels, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 12, 2013
• First Posted: June 17, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2019
• Study Completion: March 1, 2020
• Last Updated: March 8, 2022
• Results First Posted: February 9, 2022

Record last verified: 2022-02

Locations

US (1)