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Open Access Study protocol

Open randomised prospective comparative multi-centre intervention study of patients with cystic fibrosis and early diagnosed diabetes mellitus

Manfred Ballmann1*, Dominique Hubert2, Barouk M Assael3, Kai Kronfeld4, Marguerite Honer5, Reinhard W Holl6 and CFRD Study group

Author Affiliations

1 Department Paediatric Pulmonology, Paediatric clinic at St Josef Hospital, Ruhr University Bochum, Alexandrinen Strasse 5, Bochum 44197, Germany

2 Service de Pneumologie, APHP Hôpital Cochin, Paris, France

3 Ospedale Civile Maggiore, Verona, Italy

4 Interdisciplinary Centre for Clinical Trials (IZKS), University Medical Centre, Mainz, Germany

5 Mukoviszidose Institut gGmbH, Bonn, Germany

6 University of Ulm, Institute of Epidemiology and Medical Biometry, Ulm, Germany

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BMC Pediatrics 2014, 14:70  doi:10.1186/1471-2431-14-70

Published: 11 March 2014

Abstract

Background

Diabetes mellitus may be present in patients with cystic fibrosis starting in the second decade of life. The prevalence increases rapidly with increasing age. As life-expectancy increases in cystic fibrosis, cystic fibrosis related diabetes will be diagnosed more frequently in the future.

Up to date, no data are available to answer the question if cystic fibrosis related diabetes should always initially be treated by insulin therapy. Missing data regarding oral antidiabetic treatment of newly diagnosed cystic fibrosis related diabetes are an important reason to recommend insulin treatment. Several centres report the successful management of cystic fibrosis related diabetes using oral anti-diabetic drugs at least for some years. Oral therapies would be less invasive for a patient group which is highly traumatized by a very demanding therapy. Based on an initiative of the German Mukoviszidosis-Foundation, the present study tries to answer the question, whether oral therapy with repaglinide is as effective as insulin therapy in cystic fibrosis patients with early diagnosed diabetes mellitus.

Methods/Design

In all cystic fibrosis patients with an age of 10 years or older, an oral glucose tolerance test is recommended. The result of this test is classified according to the WHO cut off values. It is required to have two diabetes positive oral glucose tolerance tests for the diagnosis of diabetes mellitus.

This study is a multi-national, multicentre, open labelled, randomized and prospective controlled parallel group’s trial, with 24 months treatment.

The primary objective of this trial is to compare the glycaemic control of oral therapy with Repaglinide with insulin injections in patients with cystic fibrosis related diabetes after 2 years of treatment.

The trial should include 74 subjects showing cystic fibrosis related diabetes newly diagnosed by oral glucose tolerance test during annual screening for cystic fibrosis related diabetes.

Patients are randomised by central fax randomisation.

Primary endpoint is mean HbA1c after 24 months of treatment. Secondary endpoints are change in FEV1% predicted and change in BMI-Z-score.

Discussion

There is only one prospective study comparing oral antidiabetic drugs to insulin in the treatment of CFRD without fasting hyperglycaemia. The results regarding BMI after 6 months and 12 months showed an improvement for the insulin treated patients and were inconsistent for those treated with repaglinide. HbA1c and lung function (FEV1%pred) were unchanged for either group. The authors compared the changes -12 months to baseline and baseline to +12 months separately for each group. Therefore a direct comparison of the effect of repaglinide versus insulin on BMI, HbA1c and FEV1%pred was not presented. According to our protocol, we will directly compare treatment effects (HbA1c, BMI, FEV1%pred) in between both groups. The actual Cochrane report regarding “Insulin and oral agents for managing CFRD” stated that further studies are needed to establish whether there is clear benefit for hypoglycemic agents. We expect that the results of our study will help to address this clinical need.

Trial registration

ClinicalTrials.gov Identifier: NCT00662714

Keywords:
Cystic fibrosis; Diabetes mellitus; Lung diseases; Genetic diseases; Inborn; Repaglinide; Insulin; HbA1c; Clinical trial