Clinical trial NCT00662714: Early Diagnosis of Diabetes Mellitus in Patients With Cystic Fibrosis
Official title: Open Randomised Prospective Comparative Multi-centre Intervention Study of Patients With Cystic Fibrosis and Early Diagnosed Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Diabetes Mellitus
Lead sponsor: Mukoviszidose Institut gGmbH
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
name: Mucoviscidose-ABCF2
name: Assistance Publique - Hôpitaux de Paris
First posted: 2008-04-21
Enrollment: 73
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Is oral therapy with Repaglinide equivalent to insulin therapy with three daily injections with respect to blood glucose control, weight and pulmonary function over 2 years in patients with cystic fibrosis and secondary diabetes mellitus? That is the question examined in the phase III trial.

Detailed description: Diabetes mellitus may be present in patients with cystic fibrosis (mucoviscidosis) starting in the second decade of life. The prevalence increases rapidly with increasing age. As life-expectancy increases in CF, CF-related diabetes will be diagnosed more frequently in the future. Negative consequences of secondary diabetes in cystic fibrosis include:

* Catabolic metabolism
* Weight loss
* More frequent / more severe infections
* Deterioration of pulmonary function
* Reduced life-expectancy
* Diabetic micro vascular complications (retinopathy, nephropathy, neuropathy)

Up to date, no data are available to answer the question, whether secondary diabetes in CF should always be treated by insulin therapy. Several centres report the successful management of CF-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 traumatised by a very demanding therapy (multiple drugs including antibiotics, pancreas enzymes, bronchodilators, mucolysis, in addition to physiotherapy, regular inpatient iv-antibiotic therapy etc, finally lung transplants in a subgroup of patients).

Eligibility criteria: Inclusion Criteria:

Inclusion Criteria for the Screening:

* Diagnosed cystic fibrosis
* Age 10 years and older

Inclusion Criteria for the therapeutic part of the study:

* Newly diagnosed Diabetes mellitus in the screening

Exclusion Criteria:

Exclusion Criteria for Screening:

* Diabetic keto-acidosis (blood glucose \> 350 mg/dl and arterial pH \< 7.25)
* Already treated Diabetes mellitus by oral antidiabetic medication or insulin

Exclusion Criteria for the therapeutic part of the study:

* Systemic steroid therapy during the last 3 months
* Transplantation (status post TX or on the waiting list for TX)
* Beginning pulmonary insufficiency, FEV1 \< 35% at pulmonary function test in stable condition
* Pregnancy
* Already diagnosed and treated diabetes mellitus
* Patients with diabetic keto-acidosis (blood glucose \> 350 mg/dl and arterial pH \< 7.25) with or without diabetic coma
* Severe liver insufficiency (chronic hepatitis B, AST or ALT twice the upper limit of normal, Quick's value \< 70% which is a contraindication to use Repaglinide)
* Treatment with an indispensable important drug which contraindicates Repaglinide
* PEG/ gastric tube/ total parenteral alimentation for more than 4 weeks during the study
* CF-patients with type 1 diabetes
* Not patient's consent to randomisation and therapeutic trial
* Participation on other medical trial

Primary outcomes:
measure: HbA1c
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Universitätsklinik für Kinder- und Jugendheilkunde
city: Wien
country: Austria
facility: Universitätsklinik für Kinder- und Jugendheilkunde
city: Lille
country: France
facility: CRCM adultes
city: Lyon
country: France
facility: CRCM adultes, Centre Hospitalier Lyon Sud
city: Paris
country: France
facility: APHP, CRCM pediatrique, Hopital Necker
city: Paris
country: France
facility: APHP, CRCM pediatrique, Hopital Robert Debre
city: Paris
country: France
facility: APHP, CRCM pediatrique, Hopital Cochin
city: Strasbourg
country: France
facility: CRCM adultes, Hopital Civil
city: Berlin
country: Germany
facility: Helios Klinikum Emil von Behring
city: Berlin
country: Germany
facility: Heliosklinikum Berlin-Buch
city: Bremen
country: Germany
facility: Prof.-Hess-Kinderklinik/ Zentralkrankenhaus
city: Bremen
country: Germany
facility: Zentralkrankenhaus "Links der Weser"
city: Düsseldorf
country: Germany
facility: Universitätskinderklinik Düsseldorf
city: Erlangen
country: Germany
facility: Klinik für Kinder und Jugendliche Erlangen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Essen
country: Germany
facility: Ruhrlandklinik Essen
city: Frankfurt
country: Germany
facility: Zentrum für Kinderheilkunde Frankfurt
city: Frankfurt
country: Germany
facility: Med. Klinik II, Allergologie und Pneumologie
city: Gerlingen
country: Germany
facility: Klinik Schillerhöhe
city: Greifswald
country: Germany
facility: Klinik und Poliklinik für Kinder- und Jugendmedizin
city: Hamburg
country: Germany
facility: Altona - Klinik
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Abt. Kinderheilkunde
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, CF-Ambulanz f. Erwachsene
city: Heidelberg
country: Germany
facility: Klikum der Universität Heidelberg, Kinderklinik
city: Homburg
country: Germany
facility: Universitätsklinik für Kinder- und Jugendmedizin
city: Kassel
country: Germany
facility: Kinderkrankenhaus Park Schönfeld
city: Kiel
country: Germany
facility: Städtisches Krankenhaus Kiel
city: Köln
country: Germany
facility: Klinik und Poliklinik für allgemeine Kinderheilkunde
city: Mainz
country: Germany
facility: Universitätsklinik Mainz
city: Münster
country: Germany
facility: Clemenshospital
city: Oldenburg
country: Germany
facility: Elisabeth Kinderkrankenhaus
city: Osnabrück
country: Germany
facility: Kinderhospital Osnabrück
city: Passau
country: Germany
facility: Kinderklinik Dritter Orden, Sozialpädiatrisches Zentrum
city: Tübingen
country: Germany
facility: Universitätsklinik für Kinder- und Jugendmedizin
city: Würzburg
country: Germany
facility: Julius-Maximilians Universität, Kinderpoliklinik
city: Verona
country: Italy
facility: Centro Fibrosi Cistica
Study officials:
affiliation: St. Josef Hospital,Alexandrinenstrasse 5,44791 Bochum, Germany
name: Manfred Ballmann, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Zentralinstitut für Biomedizinische Technik Ulm
name: Reinhard Holl, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Onady GM, Stolfi A. Drug treatments for managing cystic fibrosis-related diabetes. Cochrane Database Syst Rev. 2020 Oct 19;10(10):CD004730. doi: 10.1002/14651858.CD004730.pub5.
citation: Ballmann M, Hubert D, Assael BM, Staab D, Hebestreit A, Naehrlich L, Nickolay T, Prinz N, Holl RW; CFRD Study Group. Repaglinide versus insulin for newly diagnosed diabetes in patients with cystic fibrosis: a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 2018 Feb;6(2):114-121. doi: 10.1016/S2213-8587(17)30400-X. Epub 2017 Dec 5.
citation: Ballmann M, Hubert D, Assael BM, Kronfeld K, Honer M, Holl RW; CFRD Study group. Open randomised prospective comparative multi-centre intervention study of patients with cystic fibrosis and early diagnosed diabetes mellitus. BMC Pediatr. 2014 Mar 11;14:70. doi: 10.1186/1471-2431-14-70.
citation: Schmid K, Fink K, Holl RW, Hebestreit H, Ballmann M. Predictors for future cystic fibrosis-related diabetes by oral glucose tolerance test. J Cyst Fibros. 2014 Jan;13(1):80-5. doi: 10.1016/j.jcf.2013.06.001. Epub 2013 Jun 25.