Cystic fibrosis: a hereditary inflammatory process

ISRCTN	ISRCTN03484127
DOI	https://doi.org/10.1186/ISRCTN03484127
Protocol serial number	NTR91
Sponsor	University Medical Centre Utrecht (UMCU) (The Netherlands)
Funder	The Netherlands Organization for Scientific Research (NWO) (The Netherlands)

Submission date: 12/09/2005
Registration date: 12/09/2005
Last edited: 17/09/2008

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Mr S W J Terheggen-Lagro
Scientific

Universitair Medisch Centrum, locatie AZU
CF-Centrum
Huispostnummer B03.237
P.O.Box 85500
Utrecht
3508 GA
Netherlands

Phone	+31 (0)30 250 4000
Email	s.terheggen@umcutrecht.nl

Study information

Primary study design	Interventional
Study design	Randomised, double blind, placebo controlled, parallel group trial
Secondary study design	Randomised controlled trial
Scientific title
Study objectives	One out of 3600 new-born children in the Netherlands has cystic fibrosis (CF). It is an autosomal recessive disease and about 70% of the Dutch CF-patients are homozygous for the delta-F508 mutation. Although the genetic mutation is identical in this group of patients, the pulmonary disease is very diverse. Causative factors are environmental and also co-genetic ones. Morbidity is caused by chronic inflammation and infection of the lungs, which leads to irreversible lung damage. Neutrophils play a key role in the inflammatory cascade. It is assumed that parts of the acute inflammatory response of the neutrophil (chemotaxis/IL8 ± adhesion/selectines ± activation/TNFa ± production of e.g. superoxides or myeloperoxidase ±tissue destruction) play an important role in the inflammatory process in CF. There is a higher concentration of mediators (IL-8, sICAM1, sE-Selectin, TNFa) in patients with CF than in other patients with airway infections. The CFTR protein acts not only as a Cl channel but also as a Na/H antiport and influences the intracellular pH. This might affect the functional activity of the neutrophil. Recently, new activation markers (MoPhabs A17 and A27) located on leukocytes were described that may be an early sign of pulmonary inflammation. To be able to predict and intervene in the inflammatory process would improve the prognosis especially in young children before the process of irreversible lung damage. The use of new and powerful inhaled corticosteroid medication enables us to give anti-inflammatory therapy to young children without the systemic side-effects of orally administered steroids.
Ethics approval(s)	Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studied	Cystic fibrosis
Intervention	Inhaled HFA-Beclomethasone Diproprionate (Qvar®) 200 mcg twice daily by aerochamber or a placebo (also inhaled by aerochamber).
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Inhaled HFA-Beclomethasone Diproprionate
Primary outcome measure(s)	Pulmonary 1. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), residual volume (RV)/total lung capacity (TLC) % after 3 years 2. Rint measurements
Key secondary outcome measure(s)	Immunological: 1. Neutrophil markers: MoPhabs A17 and A27, CD11b, CD11a 2. Interleukin-8 (IL-8), soluble intercellular adhesion molecule 1 (sICAM1), sE-Selectin, tumour necrotising factor alpha (TNFa) 3. End tidal carbon monoxide in exhaled breath Microbiological: 1. Respiratory pathogens in culture Serological: 1. Seroconversion to anti-pseudomonal antibodies Clinical: 1. Adverse events 2. Clinical parameters (body weight, height, fat free mass) 3. Number of pulmonary exacerbations 4. Antimicrobial agent use 5. Quality of life questionnaire scores Radiological: 1. Chest radiograph scored by CF chest radiograph scoring systems
Completion date	01/12/2005

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	2 Years
Upper age limit	10 Years
Sex	All
Target sample size at registration	60
Key inclusion criteria	For 3-years randomised controlled trial: 1. CF diagnosis as confirmed by sweat chloride test and/or genotyping 2. CF-patients 2 - 10 years old 3. Informed consent 4. Capable of using inhaled corticosteroids by aerochamber 5. Compliant to regular therapy
Key exclusion criteria	For 3-years randomised controlled trial: 1. CF-patients less than 2 years 2. CF-patients greater than 10 years 3. Use of anti-inflammatory therapy in a period of 2 months before inclusion (orally administered steroids, inhaled corticosteroids and non-steroid anti-inflammatory drugs, non-steroidal anti-inflammatory drugs [NSAIDs]) 4. Disease, other than CF, that affects growth 5. Participation in another study
Date of first enrolment	01/01/2002
Date of final enrolment	01/12/2005

Locations

Countries of recruitment

Netherlands

Study participating centre

Universitair Medisch Centrum, locatie AZU

Utrecht
3508 GA
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan