Early Diagnosis of Diabetes Mellitus in Patients With Cystic Fibrosis

• ClinicalTrials.gov Identifier: NCT00662714
• Recruitment Status: Completed
• First Posted: April 21, 2008
• Last Update Posted: July 10, 2012
• Sponsor: Mukoviszidose Institut gGmbH
• Collaborators: Novo Nordisk A/S; Mucoviscidose-ABCF2; Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Mukoviszidose Institut gGmbH

Tracking Information

• First Submitted Date: April 17, 2008
• First Posted Date: April 21, 2008
• Last Update Posted Date: July 10, 2012
• Study Start Date: September 2001
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 18, 2008): HbA1c [ Time Frame: 2 years ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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).

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Cystic Fibrosis
• Diabetes Mellitus

Intervention

• Drug: Repaglinide
  oral; initial dose: 3x 0.5mg/d; 2 years
• Drug: short-acting Insulin (Actrapid)
  initial dose: 3x 0.05E/kg/d, injected; 2 years
  Other Name: Actrapid

Study Arms

• Experimental: 1
  Repaglinide; oral
  Intervention: Drug: Repaglinide
• Active Comparator: 2
  short-acting Insulin (Actrapid)
  Intervention: Drug: short-acting Insulin (Actrapid)

Publications *

• Onady GM, Stolfi A. Drug treatments for managing cystic fibrosis-related diabetes. Cochrane Database Syst Rev. 2020 Oct 19;10:CD004730. doi: 10.1002/14651858.CD004730.pub5.
• 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. Erratum in: Lancet Diabetes Endocrinol. 2019 Apr;7(4):e4.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 6, 2012): 73
• Original Estimated Enrollment (submitted: April 18, 2008): 74
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, France, Germany, Italy

Administrative Information

• NCT Number: NCT00662714
• Other Study ID Numbers: F01/01 CF-RD
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Mukoviszidose Institut gGmbH
• Study Sponsor: Mukoviszidose Institut gGmbH

Collaborators

• Novo Nordisk A/S
• Mucoviscidose-ABCF2
• Assistance Publique - Hôpitaux de Paris

Investigators

• Principal Investigator: Manfred Ballmann, Prof. Dr.; St. Josef Hospital,Alexandrinenstrasse 5,44791 Bochum, Germany
• Principal Investigator: Reinhard Holl, Prof.; Zentralinstitut für Biomedizinische Technik Ulm

• PRS Account: Mukoviszidose Institut gGmbH
• Verification Date: July 2012