Cystic Fibrosis (CF) Exacerbation and Insulin Treatment

Study Overview
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Brief Summary
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The purpose of the study is to evaluate whether insulin treatment during pulmonary exacerbation (PE) in patients with Cystic Fibrosis (CF)and normoglycemia improves their short term outcome by normalizing the glycemic profile and enhancing recovery. the investigators would like to evaluate whether insulin treatment during exacerbation improves both the general clinical condition of these patients and also has a protecting effect on ß-cells by preventing the deleterious effect of chronic hyperglycemia.

Detailed Description
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The life expectancy of patients with cystic fibrosis (CF) has increased over the last decades due to improved understanding of the disease and new treatments. CF patients who live longer develop glucose intolerance and cystic fibrosis related diabetes (CFRD), in fact, routine annual screening by Oral Glucose Tolerance Tests (OGTT) shows that the prevalence of CFRD increases with age. CFRD is primarily an insulinopenic condition characterized by an impaired and delayed insulin secretion, as a consequence of fibrosis in the exocrine pancreatic tissue that compromises the ß-cell function. The occurrence of CFRD is significantly related to increased morbidity and mortality. Based on data from the CF Patients Registry in the USA, the mortality rate of patients with CFRD is six-fold higher than that of patients without CFRD. Our pilot study proved that during pulmonary exacerbation (PE), CF patients with Normal Glucose Tolerance (NGT) exhibited early latent diabetic glucose intolerance in Oral Glucose Tolerance Test(OGTT) which becomes completely normalized 3-4 weeks after resolution of PE. These patients who are considered to be normoglycemic may experience relatively long periods of hyperglycemia during recurrent events of pulmonary infections. Chronically increased glucose values during PE have an adverse impact on pulmonary function both during PE and in the long-term. Hyperglycemia may increase the duration and extent of recovery from PE. Furthermore it may impair the ability to overcome lung infections by directly stimulating the growth of respiratory pathogens. Finally, hyperglycemia per-se during stressful conditions may worsen the general outcome. Insulin therapy is considered routine treatment for patients with CFRD. In addition to normalizing glucose levels, insulin has a beneficial effect on general pulmonary function and nutritional status, possibly due to its anabolic effect. No routine or formal guidelines for treating PE hyperglycemia are currently available. Normal Glucose Tolerance (NGT)patients, who are hyperglycemic during PE only, are generally not intensively treated for this condition, except if the treating physician decides on interventional insulin treatment. Some patients may experience relatively long periods of hyperglycemia during recurrent events of pulmonary infections.

Official Title
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Evaluation of Glucose Tolerance and Insulin Treatment in Non Diabetic Patients With Cystic Fibrosis During Acute Pulmonary Exacerbation

Conditions
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Cystic Fibrosis, Impaired Glucose Tolerance, Pulmonary Exacerbation

Intervention / Treatment
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* Drug: novorapid / humalog short acting insulin
* Drug: Novo Rapid Insulin (Novonordisk)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of CF according to standard criteria Pancreatic insufficiency Age > 10 years Normal oral glucose tolerance test (OGTT) in the past 12 month. Acute pulmonary exacerbation (PE) according to the treating physician requires treatment with intravenous antibiotics Exclusion Criteria: CF-related diabetes/impaired glucose tolerance test (IGTT) in a mixed meal tolerance test performed during full remission from pulmonary exacerbation

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: insulin<br>patients who will get insulin with main meals during Intravenous (IV) antibiotic therapy due to pulmonary exacerbation | Drug: novorapid / humalog short acting insulin<br>* 1-4 units will be injected Subcutaneously (SC), before every main meal.<br>* Other names: Humalog insulin;Drug: Novo Rapid Insulin (Novonordisk)<br>* Novo Rapid Insulin (Novonordisk) will be administered before each main meal 1-4 units depends on the patients weight<br>* Other names: Humalog insulin lispro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| delta Forced Expiratory Volume in 1 second (FEV1%) predicted | change in lung function parameter %FEV1 predected from baseline before the exacerbatio to day 0, the day of hospitalization due to the pulmonary exacerbation and to day 14, after 2 weeks of Intra Venous (IV)Antibiotic therapy, due to Pulmonary Exacerbation (PE). | day 0 of the pulmonary exacerbation, to day 14 of the pulmonary exacerbation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in Body Mass Index (BMI) | weight and hight will be measured on arrival to hospital (day 0)of the pulmonary exacerbation and again on day 14 of the pulmonary exacerbation and. BMI will be calculated and compared to BMI perior to the exacerbation | baseline BMI will be compared with BMI on day 0- the day of hospitalization due to the pulmonary exacerbation, and to day 14, after 2 weeks of Intra Venous (IV)Antibiotic therapy, due to Pulmonary Exacerbation (PE). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Normal Glucose Tolerance Test, Mixed Meal Tolerance Test, Cystic Fibrosis, Pulmonary Exacerbation, Impaired Glucose Tolerance Test, Insulin Therapy