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| ID | Type | Description | Link |
|---|---|---|---|
| P60DK020579 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Washington University School of Medicine | OTHER |
| National Institutes of Health (NIH) | NIH |
| Novo Nordisk A/S | INDUSTRY |
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
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The purpose of this study is to provide the necessary data and experience to design a larger, full scale clinical trial to determine if a certain medicine (repaglinide), which increases the amount of insulin secreted by the pancreas, can improve the nutritional status and pulmonary function of adolescents and young adults with cystic fibrosis and prediabetes by improving blood glucose control. The investigators are also trying to determine the relationship between systemic inflammatory factors and glucose impairment.
As people with Cystic Fibrosis (CF) are living well into adulthood new complications are arising. CF-Related Diabetes (CFRD) has emerged as a major complication. Years prior to the diagnosis of CFRD, patients have decreasing insulin secretion, glucose intolerance, deteriorating pulmonary function, and nutritional impairment. There are no current standard recommendations for the treatment of CF patients with prediabetes, and there is little evidence that treatment of this prediabetic state in CF patients will prevent the deterioration of the lung function, nutritional status and potentially slow the progression to manifest CFRD.
To determine the feasibility of testing this hypothesis, we will perform a pilot, double-blinded, randomized controlled trial in 20 CF pancreatic insufficient patients ages of 12 to 24 years old with impaired glucose tolerance test (IGT) or CFRD without fasting hyperglycemia (CFRD-No FH) and assign them to either placebo or Repaglinide 0.5 mg PO 3 - 4 times a day before meals for two years. Patients will monitor their blood glucose daily and will be followed every 3 months for 2 years to determine changes in nutritional status by BMI and DEXA, lung function tests, frequency of hospitalizations, antibiotic courses, and degree of glucose tolerance, insulin secretion and insulin sensitivity.
In addition, based on the evidence of increased inflammation in type 2 diabetes, correlation of systemic inflammatory response at different degrees of glucose tolerance and after treatment, will be assessed in these subjects, as well as in another 20 CF pancreatic insufficient matched patients with normal glucose tolerance who will be studied once without intervention
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 Placebo | Placebo Comparator | 1 pill before each meal 3-4 times a day for 2 years. All subjects had abnormal glucose tolerance. Subjects were randomized to placebo or drug. |
|
| 2. repaglinide | Experimental | repaglinide 0.5 mg before each meal 3-4 times a day for 2 years. All subjects had abnormal glucose tolerance.Subjects were randomized to placebo or drug. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| placebo | Drug | CF pancreatic insufficient patients with impaired glucose tolerance (IGT) or CFRD without fasting hyperglycemia (CFRD-No FH) by OGTT will be treated with placebo by taking 1 pill before each meal that contains more than 20 grams of carbohydrate 3-4 times a day for 2 years. |
| Measure | Description | Time Frame |
|---|---|---|
| BMI | 2 year/end of study | |
| Body Composition | Reporting % of Fat and Lean body mass | 2 year/end of study |
| CRP | 2 year/end of study |
| Measure | Description | Time Frame |
|---|---|---|
| Glucose Tolerance | We completed the OGTT at the 2 year/end of study visit. | 2-year |
| Inflammatory Markers | 2 year/end of study | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Neil H White, M.D. | Washington University School of Medicine | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
The outcome was inconclusive for this hypothesis, but the data may be valuable in future research. We are not currently sharing data from this project.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | 1 pill before each meal 3-4 times a day for 2 years. placebo: CF pancreatic insufficient patients with prediabetes by OGTT will be treated with placebo by taking 1 pill before each meal that contains more than 20 grams of carbohydrate 3-4 times a day for 2 years. |
| FG001 | 2. Repaglinide | repaglinide 0.5 mg before each meal 3-4 times a day for 2 years. repaglinide: CF pancreatic insufficient patients with prediabetes by OGTT will be treated with repaglinide 0.5 mg before each meal that contains more than 20 grams of carbohydrate 3-4 times a day for 2 years. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Patients attended the Washington University CF Clinics between 2006 and 2008.
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| ID | Title | Description |
|---|---|---|
| BG000 | Patients Who Received Placebo | All participants were receiving ADEK vitamins and pancreatic enzyme replacement. Patients were required to be clinically stable, without evidence of deterioration from previous pulmonary function tests (PFTs) for 3-months prior to the study and without CF exacerbation or hospitalization for 2-months prior to the study. Additionally, patients were required to have maintained stable weight within 5% variance for 3-months prior to participation. Exclusion criteria included fasting blood glucose levels >126 mg/dL on study day, IV antibiotic or systemic steroid use within two months, oral corticosteroid usage for more than 28-days over the past 6-months, history of lung or liver transplant, elevated transaminases, allergic bronchopulmonary aspergillosis, or the inability to perform spirometry. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Patients attended the Washington University CF Clinics between 2006 and 2008. |
| 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 | BMI | Posted | Mean | Full Range | Kg/m^2 | 2 year/end of study |
|
This pilot study was designed to collect data over a 2 year time period.
Glucose diaries, and food diaries were reviewed, and safety labs were collected at each visit. Physical assessments by the PI were completed as well.
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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 | Placebo | Placebo group of CF pancreatic insufficient patients ages 12-24 years old with impaired glucose tolerance test (IGT) or CFRD without fasting hyperglycemia (CFRD-No FH). |
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A limitation of the study was the very small sample size.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ana Maria Arbelaez | Washington University in St Louis | 314-286-1138 | arbelaez_a@kids.wustl.edu |
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| ID | Term |
|---|---|
| D010188 | Exocrine Pancreatic Insufficiency |
| D003550 | Cystic Fibrosis |
| D003920 | Diabetes Mellitus |
| D018149 | Glucose Intolerance |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C072379 | repaglinide |
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| NIH |
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| repaglinide | Drug | CF pancreatic insufficient patients with impaired glucose tolerance (IGT) or CFRD without fasting hyperglycemia (CFRD-No FH) by OGTT will be treated with repaglinide 0.5 mg before each meal that contains more than 20 grams of carbohydrate 3-4 times a day for 2 years. |
|
|
| Wt Z Score |
| 2 year/end of study |
| Tanner Stage | Puberty scale measuring 1-5, 1 being least development, 5 being most development. | 2 year/end of study |
| FEV 1 | % of lung function | 2 year/end of study |
| C-Peptide | 2 year |
| BG001 | Patients Who Received Repaglinide | All participants were receiving ADEK vitamins and pancreatic enzyme replacement. Patients were required to be clinically stable, without evidence of deterioration from previous pulmonary function tests (PFTs) for 3-months prior to the study and without CF exacerbation or hospitalization for 2-months prior to the study. Additionally, patients were required to have maintained stable weight within 5% variance for 3-months prior to participation. Exclusion criteria included fasting blood glucose levels >126 mg/dL on study day, IV antibiotic or systemic steroid use within two months, oral corticosteroid usage for more than 28-days over the past 6-months, history of lung or liver transplant, elevated transaminases, allergic bronchopulmonary aspergillosis, or the inability to perform spirometry. |
| BG002 | Total | Total of all reporting groups |
| Count of Participants |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| BMI | Mean | Full Range | Kg/m^2 |
|
| Wt Z score | Mean | Full Range | Z score |
|
| Fat % | Mean | Full Range | % Fat mass |
|
| Lean % | Mean | Full Range | % Lean mass |
|
| Tanner stage | This is a measurement of puberty development. This is a 1-5 scale describing 1 as the least developed and 5 as the most developed in puberty. | Mean | Full Range | units on a scale |
|
| FEV 1 | Mean | Full Range | % of lung function |
|
| Fasting Glucose | This was the baseline glucose in a 2 hour oral glucose tolerance test. (OGTT) | Mean | Full Range | mg/dl |
|
| 2 hour glucose | Final glucose sample in a 2 hour OGTT. | Mean | Full Range | mg/dl |
|
| Fasting C-Peptide | Mean | Full Range | mg/dl |
|
| 2 hour c-peptide | final c-peptide measurement at the end of 2 hour OGTT. | Mean | Full Range | mg/dl |
|
| Inflammatory marker | baseline values collected during a 2 hour OGTT. | Mean | Full Range | pg/ml |
|
| CRP | inflammatory marker | Mean | Full Range | mg/L |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Body Composition | Reporting % of Fat and Lean body mass | Posted | Mean | Full Range | % body mass | 2 year/end of study |
|
|
|
| Primary | CRP | Posted | Mean | Full Range | mg/L | 2 year/end of study |
|
|
|
| Secondary | Glucose Tolerance | We completed the OGTT at the 2 year/end of study visit. | Posted | Mean | Full Range | mg/dl | 2-year |
|
|
|
| Secondary | Inflammatory Markers | Posted | Mean | Full Range | pg/ml | 2 year/end of study |
|
|
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| Secondary | Wt Z Score | Posted | Mean | Full Range | Z score | 2 year/end of study |
|
|
|
| Secondary | Tanner Stage | Puberty scale measuring 1-5, 1 being least development, 5 being most development. | Posted | Mean | Full Range | units on a scale | 2 year/end of study |
|
|
|
| Secondary | FEV 1 | % of lung function | Posted | Mean | Full Range | % lung function | 2 year/end of study |
|
|
|
| Secondary | C-Peptide | Posted | Mean | Full Range | pg/ml | 2 year |
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | Repaglinide | Repaglinide intervention group of CF pancreatic insufficient patients ages 12-24 years old with impaired glucose tolerance test (IGT) or CFRD without fasting hyperglycemia (CFRD-No FH). | 0 | 8 | 0 | 8 | 0 | 8 |
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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 |
| D006943 | Hyperglycemia |
| IL8 |
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| TNF alpha |
|