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| Name | Class |
|---|---|
| Children's Hospital of Philadelphia | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sitagliptin | Experimental | The dose of sitagliptin (Januvia®) 100 mg tablet will be taken orally each morning for 6 months. |
|
| Placebo | Placebo Comparator | Placebo tablet will be taken orally each morning for 6 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael M Rickels, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Philadelphia and University of Pennsylvania | Philadelphia | Pennsylvania | 19194 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34406395 | Derived | 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. |
| Label | URL |
|---|---|
| Published paper for this study titled: "Effect of Sitagliptin on Islet Function in Pancreatic Insufficient Cystic Fibrosis With Abnormal Glucose Tolerance". | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sitagliptin | The dose of sitagliptin (Januvia®) 100 mg tablet will be taken orally each morning for 6 months. 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. |
| FG001 | Placebo | Placebo tablet will be taken orally each morning for 6 months. 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sitagliptin | The dose of sitagliptin (Januvia®) 100 mg tablet will be taken orally each morning for 6 months. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Median | Inter-Quartile Range | Insulin230 µU/mL | Baseline and 6 months |
|
6 Months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sitagliptin | The dose of sitagliptin (Januvia®) 100 mg tablet will be taken orally each morning for 6 months. 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mild allergic reaction to study drug | Skin and subcutaneous tissue disorders | Systematic Assessment | Rash or mild allergic reaction to the study drug. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Paola Alvarado | University of Pennsylvannia | 215-746-2081 | paola.alvarado@pennmedicine.upenn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 10, 2015 | Oct 7, 2020 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 2, 2018 | Oct 7, 2020 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| D010188 | Exocrine Pancreatic Insufficiency |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D000068900 | Sitagliptin Phosphate |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
|
| 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. |
|
| BG001 | Placebo | Placebo tablet will be taken orally each morning for 6 months. 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 | Sitagliptin | The dose of sitagliptin (Januvia®) 100 mg tablet will be taken orally each morning for 6 months. 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. |
| OG001 | Placebo | Placebo tablet will be taken orally each morning for 6 months. 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. |
|
|
| 0 |
| 13 |
| 0 |
| 13 |
| 1 |
| 13 |
| EG001 | Placebo | Placebo tablet will be taken orally each morning for 6 months. 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. | 0 | 13 | 0 | 13 | 0 | 13 |
|
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| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D011719 |
| Pyrazines |