The purpose of this trial is primarily to assess the efficacy of inhaled mannitol compared with a true placebo in subjects with cystic fibrosis aged 6 to 17 years.We hypothesize that inhaled mannitol will improve the overall health and hygiene of…
ID
Source
Brief title
Condition
- Respiratory disorders congenital
- Congenital respiratory tract disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the effect of eight weeks of twice-daily treatment with inhaled
dry powder mannitol on lung function (FEV1) in subjects with CF who are aged
six to seventeen years
Secondary outcome
• To determine the effect of inhaled mannitol on FVC;
• To determine the effect of inhaled mannitol on FEF25-75 (exploratory
objective) and
• To assess the safety of inhaled mannitol.
• To evaluate the difference in treatment induced sputum weight in subjects
treated with inhaled mannitol compared to those treated with placebo.
Background summary
Inhaled mannitol is being developed as a therapeutic agent for the treatment of
cystic fibrosis and other diseases characterized by difficult to clear,
thickened respiratory mucus. The mucoactive effects of inhaled mannitol have
been examined in several acute and short term studies and now warrant further
investigation.
Whilst paediatric and adolescent subjects (aged <18 years) have been studied in
previous phase III clinical trials of inhaled mannitol that assessed
improvements in lung function [10, 11], there are remaining uncertainties
around the effect size of inhaled mannitol 400 mg b.d. in this population.
While data from the previous phase III studies suggest the effect of the 400 mg
dose was consistent across age groups, the 50 mg control groups also had some
improvement in lung function in these age groups. Thus the effect size in these
age groups remains unclear.
Different trials demonstrate the efficacy of mannitol:
-mannitol as bronchial provocation test
-mucociliary clearance studies in cystic fibrosis, bronchiectasis ans asthma
-therapeutic studies in bronchiectasis
-therapeutic studies in cystic fibrosis
Study objective
The purpose of this trial is primarily to assess the efficacy of inhaled
mannitol compared with a true placebo in subjects with cystic fibrosis aged 6
to 17 years.
We hypothesize that inhaled mannitol will improve the overall health and
hygiene of the lung through regular and effective clearing of the mucus load.
On commencing treatment, we expect an acute clearance of the retained musus and
with twice daily use, ongoing mucus clearance to be associated with reduced
mucus production.
Study design
Randomised, multicentre, double-blind, placebo-controlled, crossover
Intervention
After satisfying all inclusion and exclusion criteria, subjects will be given a
mannitol tolerance test (MTT). Those with a negative MTT result will be
randomized to receive during 8 weeks B.D. 400mg of mannitol by inhalation or
placebo. After a wash-out period of 8 weeks, subjects switch treatment for
another 8 weeks period of time.
Study burden and risks
see flow-chart on page 6 of the protocol.
regarding the risks, please see ICF
Rodborough road 20
Frenchs Forest NSW 2086
AU
Rodborough road 20
Frenchs Forest NSW 2086
AU
Listed location countries
Age
Inclusion criteria
1. personally provide, or have a legal guardian povide written informed consent to participate in the trial, according to local regulations;
2. RhDNase and maintenance antibiotic use is allowed but treatment must have been established at least 3 months prior to screening. The subject must remain on rhDNase and/or maintenance antibiotics for the duration of the trial. The subject must not commence treatment with rhDNase or maintenance antibiotics during the trial;
3. Have a confirmed diagnosis of cystic fibrosis (sweat test result >=60mEq/L chloride and/or genotyping showing two identifiable mutations consistent with a diagnosis of cystic fibrosis);
4. Be aged >= 6 years and < 18 years;
5. Have a percentage of predicted FEV1 of >=30% and <=90% at screening (visit 0). Percentage of predicted FEV1 will be calculated using Wang for children <8years, and using NHanes III for those >=8 years; and
6. Be able to perform all the techniques necessary to measure lung function.
Exclusion criteria
1. be using maintenance nebulised hypertonic saline
2. be considered "terminally ill"; eligible for lung transplantation, or have received a lung transplant previously;
3. require home oxygen or assisted ventilation;
4. have had an episode of massive haemoptysis defined as acute bleeding >=240ml in a 24 hour period and/or recurrent bleeding >=100ml/day over several days in the three-months prior to screening (visit 0);
5. have a known intolerance to mannitol;
6. be taking non-selective beta-blockers;
7. in the three months prior to screening (visit 0) have had a myocardial infarction; a cerebral vascular accident; major ocular, abdominal, chest or brain surgery;
8. have a known cerebral, aortic or abdominal aneurysm;
9. be currently participating in, or have participated in another investigative drug trial within four weeks of screening (visit 0);
10. be pregnant or breastfeeding, or plan to become pregnant whilst in the trial;
11. for females of childbearing potential, be using an unreliable form of contraception (at the discretion of the investigator)
12. have any concomitant medical, psychiatric, or social condition that, in the investigator's opinion, would put the subject at significant risk, may confound the results or may significantly interfere with the subject's participation in the trial; or
13. have a 'failed' or 'incomplete' mannitol tolerance test
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-002699-14-NL |
| CCMO | NL41925.078.13 |