Treatment of Dysglycemia Using Sitagliptin in Adolescents With Cystic Fibrosis

Treatment of Dysglycemia Using Sitagliptin in Adolescents With Cystic Fibrosis.

This pilot study will be conducted in adolescents with cystic fibrosis (CF) without diabetes but with abnormal glucose tolerance, and will assess the effects of sitagliptin on glucose regulation. An oral glucose tolerance test (OGTT) and a mixed meal tolerance test (MMTT), will be performed at baseline and again ~4 weeks after treatment with study drug. We will also look at blood sugars throughout the day using a continuous glucose monitor (CGM) before each time the MMTT/OGTT are performed. Several hormones that may affect the way the body regulates blood sugars will be measured in blood when the OGTT and MMTT are done. We will assess the effect this medicine has on blood sugars (using CGM) and the effect the medicine has on the hormones measured during the OGTT and MMTT.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Sitagliptin

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with CF between 13 and <21 yrs old
• Known impaired or indeterminate glucose tolerance (based on a prior OGTT)
• No history of CFRD

Exclusion Criteria:

• Insulin use in the last two months
• Acute pulmonary exacerbation / oral corticosteroid use in the last 6 weeks
• History of pancreatitis in the last 12 months
• Skin rashes or conditions that may affect CGM placement and wear
• Pregnancy or intent on becoming pregnant
• Patients on growth hormone therapy
• Renal insufficiency with creatinine clearance <50 ml/min (based on Schwartz formula)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitagliptin; Treatment with sitagliptin	Drug: Sitagliptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to sitagliptin	Baseline and stimulated C-peptide levels (using mixed meal tolerance test) before and after treatment with sitagliptin.	Change from baseline to ~4 weeks of study drug
Response to sitagliptin	Change in glycemic variability using continuous glucose monitoring data before and after treatment with dipeptidyl peptidase-4 inhibitor.	Change from baseline to ~4 weeks of study drug
Response to sitagliptin	Change in incretins concentrations (glucagon like peptide 1; glucose-dependent insulinotropic polypeptide) in response to study drug.	Change from baseline to ~4 weeks of study drug
Response to sitagliptin	Change in incretin (glucagon like peptide 1; glucose-dependent insulinotropic polypeptide) concentrations in response to study drug.	Change from baseline to ~4 weeks of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta-cell function	Beta-cell function will be measured using mixed meal tolerance tests (MMTT) and oral glucose tolerance tests (OGTT), assessing maximum concentration and area under the curve (AUC) of glucose, insulin and c-peptide for both OGTT and MMTT.	Change from baseline to ~4 weeks of study drug
Continuous glucose monitoring (CGM)	Baseline and post-treatment changes in glycemic variability using CGM, including mean amplitude of glycemic excursion (MAGE), peak post-prandial blood sugars, and glucose area under the curve.	change from baseline to ~4 weeks of study drug

Collaborators and Investigators

• Sponsor: Nemours Children's Clinic
• Investigators: Principal Investigator: Larry A Fox, MD, Nemours Children's Clinic

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: October 26, 2012
• First Submitted That Met QC Criteria: November 1, 2012
• First Posted (Estimate): November 4, 2012

Study Record Updates

• Last Update Posted (Estimate): June 14, 2016
• Last Update Submitted That Met QC Criteria: June 10, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: adolescents; cystic fibrosis; incretins; sitagliptin; CF; GIP; GLP1; beta cell function; CFRD
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: CFRD-01