Early Diagnosis of Diabetes Mellitus in Patients With Cystic Fibrosis

NCT ID: NCT00662714

Last Updated: 2012-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-09-30
• Study Completion Date: 2011-12-31

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).

Conditions

Cystic Fibrosis; Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Repaglinide; oral

Group Type: EXPERIMENTAL

Repaglinide

Intervention Type: DRUG

oral; initial dose: 3x 0.5mg/d; 2 years

2

short-acting Insulin (Actrapid)

Group Type: ACTIVE_COMPARATOR

short-acting Insulin (Actrapid)

Intervention Type: DRUG

initial dose: 3x 0.05E/kg/d, injected; 2 years

Interventions

Repaglinide

oral; initial dose: 3x 0.5mg/d; 2 years

Intervention Type: DRUG

short-acting Insulin (Actrapid)

initial dose: 3x 0.05E/kg/d, injected; 2 years

Intervention Type: DRUG

Other Intervention Names

Actrapid

Eligibility Criteria

Inclusion Criteria

• Diagnosed cystic fibrosis
• Age 10 years and older

• Newly diagnosed Diabetes mellitus in the screening

Exclusion Criteria

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

• 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

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

Mucoviscidose-ABCF2

UNKNOWN

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: collaborator

Mukoviszidose Institut gGmbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manfred Ballmann, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

St. Josef Hospital,Alexandrinenstrasse 5,44791 Bochum, Germany

Reinhard Holl, Prof.

Role: PRINCIPAL_INVESTIGATOR

Zentralinstitut für Biomedizinische Technik Ulm

Locations

Universitätsklinik für Kinder- und Jugendheilkunde

Graz, , Austria

Universitätsklinik für Kinder- und Jugendheilkunde

Vienna, , Austria

CRCM adultes

Lille, , France

CRCM adultes, Centre Hospitalier Lyon Sud

Lyon, , France

APHP, CRCM pediatrique, Hopital Necker

Paris, , France

APHP, CRCM pediatrique, Hopital Robert Debre

Paris, , France

APHP, CRCM pediatrique, Hopital Cochin

Paris, , France

CRCM adultes, Hopital Civil

Strasbourg, , France

Helios Klinikum Emil von Behring

Berlin, , Germany

Heliosklinikum Berlin-Buch

Berlin, , Germany

Prof.-Hess-Kinderklinik/ Zentralkrankenhaus

Bremen, , Germany

Zentralkrankenhaus "Links der Weser"

Bremen, , Germany

Klinik und Poliklinik für allgemeine Kinderheilkunde

Cologne, , Germany

Universitätskinderklinik Düsseldorf

Düsseldorf, , Germany

Klinik für Kinder und Jugendliche Erlangen

Erlangen, , Germany

Universitätsklinikum Essen

Essen, , Germany

Ruhrlandklinik Essen

Essen, , Germany

Zentrum für Kinderheilkunde Frankfurt

Frankfurt, , Germany

Med. Klinik II, Allergologie und Pneumologie

Frankfurt, , Germany

Klinik Schillerhöhe

Gerlingen, , Germany

Klinik und Poliklinik für Kinder- und Jugendmedizin

Greifswald, , Germany

Altona - Klinik

Hamburg, , Germany

Medizinische Hochschule Hannover, Abt. Kinderheilkunde

Hanover, , Germany

Medizinische Hochschule Hannover, CF-Ambulanz f. Erwachsene

Hanover, , Germany

Klikum der Universität Heidelberg, Kinderklinik

Heidelberg, , Germany

Universitätsklinik für Kinder- und Jugendmedizin

Homburg, , Germany

Kinderkrankenhaus Park Schönfeld

Kassel, , Germany

Städtisches Krankenhaus Kiel

Kiel, , Germany

Universitätsklinik Mainz

Mainz, , Germany

Clemenshospital

Münster, , Germany

Elisabeth Kinderkrankenhaus

Oldenburg, , Germany

Kinderhospital Osnabrück

Osnabrück, , Germany

Kinderklinik Dritter Orden, Sozialpädiatrisches Zentrum

Passau, , Germany

Universitätsklinik für Kinder- und Jugendmedizin

Tübingen, , Germany

Julius-Maximilians Universität, Kinderpoliklinik

Würzburg, , Germany

Centro Fibrosi Cistica

Verona, , Italy

Countries

Austria; France; Germany; Italy

References

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.

Reference Type: DERIVED

PMID: 33075159 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29199116 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24620855 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23809507 (View on PubMed)

Other Identifiers

F01/01 CF-RD

Identifier Type: -

Identifier Source: org_study_id