Effect of Chronic Incretin-based Therapy in Cystic Fibrosis
| Status: | Completed |
|---|---|
| Conditions: | Pulmonary |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/28/2019 |
| Start Date: | June 2013 |
| End Date: | December 14, 2018 |
A Randomized, Double-blind, Placebo Controlled Study of the Effectiveness of Chronic Incretin-based Therapy on Insulin Secretion in Cystic Fibrosis
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.
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.
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.
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.
Inclusion Criteria:
- 1) Confirmed diagnosis of CF, defined by positive sweat test or CFTR mutation analysis
according to CFF diagnostic criteria, 2) age ≥ 18y on date of consent, 3) pancreatic
insufficiency, 4) recent OGTT consistent with Indeterminate-GT, IGT, CFRD w/o fasting
hyperglycemia, or an established diagnosis of CFRD without fasting hyperglycemia, 5)
for female subjects, negative urine pregnancy test at enrollment.
Exclusion Criteria:
- 1) Established diagnosis of non-CF diabetes (i.e. T1D) or CFRD with fasting
hyperglycemia, (fasting glucose > 126 mg/dL) 2) history of clinically symptomatic
pancreatitis within last year, 3) prior lung or liver transplant, 4) severe CF liver
disease, as defined by portal hypertension, 5) fundoplication-related dumping
syndrome, 6) medical co-morbidities that are not CF-related or are unstable per
investigator opinion (i.e. history of bleeding disorders, immunodeficiency), 7) acute
illness or changes in therapy (including antibiotics) within 6 weeks prior to
enrollment, 8) treatment with oral or intravenous corticosteroids within 6 weeks of
enrollment, 9) hemoglobin <10g/dL, within 90 days of Visit 1 or at Screening, 10)
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, 11) a history of anaphylaxis, angioedema or
Stevens-Johnson syndrome, 12) Inability to perform study specific procedures (MMTT,
GPA), 13) Subjects, who in study team opinion, may be non-compliant with study
procedures.
We found this trial at
1
site
Philadelphia, Pennsylvania 19104
Principal Investigator: Michael M Rickels, MD, MS
Phone: 267-426-5135
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