Cystic Fibrosis (CF) Exacerbation and Insulin Treatment

Cystic Fibrosis (CF) Exacerbation and Insulin Treatment



Sponsor:
Hadassah Medical Organization

Purpose
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.


Drug: novorapid / humalog short acting insulinDrug: Novo Rapid Insulin (Novonordisk)

Study Type:
Interventional

Study Design:

Allocation: RandomizedEndpoint Classification: Efficacy StudyIntervention Model: Parallel AssignmentMasking: Open LabelPrimary Purpose: Treatment
O
fficial Title:
Evaluation of Glucose Tolerance and Insulin Treatment in Non Diabetic Patients With Cystic Fibrosis During Acute Pulmonary Exacerbation



Primary Outcome Measures:
delta Forced Expiratory Volume in 1 second (FEV1%) predicted [ Time Frame: day 0 of the pulmonary exacerbation, to day 14 of the pulmonary exacerbation ] [ Designated as safety issue: No ]
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).

Secondary Outcome Measures:
change in Body Mass Index (BMI) [ Time Frame: 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). ] [ Designated as safety issue: No ]
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

Estimated Enrollment:
30

Study Start Date:
June 2010

Estimated Study Completion Date:
December 2015

Estimated Primary Completion Date:
June 2015 (Final data collection date for primary outcome measure)

insulin: Experimental
patients who will get insulin with main meals during Intravenous (IV) antibiotic therapy due to pulmonary exacerbation

Drug: novorapid / humalog short acting insulin

1-4 units will be injected Subcutaneously (SC), before every main meal. Drug: Novo Rapid Insulin (Novonordisk)

Novo Rapid Insulin (Novonordisk) will be administered before each main meal 1-4 units depends on the patients weight Detailed Description:

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.

Eligibility
Ages Eligible for Study:
10 Years and older

Genders Eligible for Study:
Both


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

Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01149005

Locations
Israel
Hadassah Hospital
Jerusalem, Israel