Investigation to Identify Predictors of Response to a Treatment With Montelukast

Overview[ - collapse ][ - ]

Purpose The main aim of the study is to develop a method that allows responders to be distinguished from non-responders before long-term treatment is initiated. Subsidiary aims are to record changes in pulmonary functional parameters, NO concentrations and peak flow variability, the use of beta2 sympathomimetics and the asthma symptom score.
ConditionAsthma
InterventionDrug: montelukast
PhasePhase 4
SponsorMarien Hospital Wesel
Responsible PartyMarien Hospital Wesel
ClinicalTrials.gov IdentifierNCT00721240
First ReceivedJuly 22, 2008
Last UpdatedFebruary 16, 2010
Last verifiedJuly 2008

Tracking Information[ + expand ][ + ]

First Received DateJuly 22, 2008
Last Updated DateFebruary 16, 2010
Start DateFebruary 2006
Estimated Primary Completion DateJune 2009
Current Primary Outcome MeasuresPatients who show a bronchospasmolytic effect in their functional pulmonary test (FEV1 increased by at least 5%) within four hours of taking montelukast. [Time Frame: 14 days after run in] [Designated as safety issue: No]
Current Secondary Outcome Measuressymptom score, PEAK-Flow, rescue medication, exhaled NO [Time Frame: 2 weeks after run in and 14 weeks after run in] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleInvestigation to Identify Predictors of Response to a Treatment With Montelukast
Official TitleInvestigation to Identify Predictors of Response to a Treatment With Montelukast
Brief Summary
The main aim of the study is to develop a method that allows responders to be distinguished
from non-responders before long-term treatment is initiated. Subsidiary aims are to record
changes in pulmonary functional parameters, NO concentrations and peak flow variability, the
use of beta2 sympathomimetics and the asthma symptom score.
Detailed Description
Leukotriene antagonists (montelukast) are particularly effective as controllers before
exposure to an allergen (Leff 1998). The same applies to the treatment of
bronchoconstriction induced by physical exertion or cold air (Richter 2000). Montelukast
binds to the cysteinyl leuko¬triene-1 receptor, where it prevents leukotriene from binding.
Leukotrienes play a key role as mediators in inflammatory processes. By binding to the
receptor they cause, among other things, edema, damage to the bronchial epithelium and
bronchoconstriction. Accordingly, in addition to its anti-inflammatory activity montelukast
brings about bronchial dilation. The safety and efficacy of the drug in children have been
well documented (Knorr 1998). Hence montelukast is approved for the treatment of bronchial
asthma in children (over six months of age). As with other antiasthmatic drugs, there are
responders and nonresponders to leukotriene receptor antagonists. The proportion of
nonresponders to montelukast among children is esti¬mated to be 30% to 40%. At present the
only way to distinguish non-responders from responders is to run a treatment trial for
several weeks. If the symptom score falls, if the use of beta2 sympathomimetics is reduced,
if pulmonary function and/or the quality of life improves, it is assumed that the patient is
a responder. This method is not only tedious but also unsafe, since a change is the
aforementioned parameters could occur spontaneously, without this being reliably
attributable to the influence of the drug. In the planned study approximately 30 children
with asthma of GINA classes 2 and 3 will be regularly examined for pulmonary function,
symptom score and nitrogen monoxide (NO). First, however, the acute pharmacologic effect of
a single dose of montelukast will be deter¬mined over a period of four hours by measuring
pulmonary function and levels of exhaled nitrogen monoxide (NO).

4.2.1. Questions addressed:

Is it possible to discriminate between responders and nonresponders at a very early stage on
the basis of the acute pharmacologic effect of montelukast? Does this classification agree
with the results after 12 weeks of treatment?

4.2.2. Hypothesis:

Patients who show a bronchospasmolytic effect in their functional pulmonary test (FEV1
increased by at least 5%) within four hours of taking montelukast also show a positive
response (defined as a combination of at least two variables (see section on the definition
of responders/non-responders during treatment)) after 12 weeks of treatment. Conversely,
patients who show no acute effect do not have a positive response during long-term therapy.

In other words, the results of the acute pharmacologic effect correspond to the effect
during long-term therapy.

5. Aim of the study:

The main aim of the study is to develop a method that allows responders to be distinguished
from non-responders before long-term treatment is initiated. Subsidiary aims are to record
changes in pulmonary functional parameters, NO concentrations and peak flow variability, the
use of beta2 sympathomimetics and the asthma symptom score.

6. Patient selection:

The study will include approximately 30 patients aged 6 to 14 years with diagnosed bronchial
asthma who have been on constant anti-inflammatory therapy for at least four weeks (GINA
classes 2 and 3).

7. Study design:

This investigation is a single-center, two-phase, single-arm study. In order to detect a
potential placebo effect, the treatment phase will be preceded by a single-blinded two-week
placebo run-in phase, followed by a 12 week open-label treatment phase.
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionAsthma
InterventionDrug: montelukast
5mg montelukast once daily for 12 weeks
Other Names:
Singulair ; MK-476
Study Arm (s)Experimental: single-arm
This investigation is a single-center, two-phase, single-arm study. In order to detect a potential placebo effect, the treatment phase will be preceded by a single-blinded two-week placebo run-in phase, followed by a 12 week open-label treatment phase.

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment50
Estimated Completion DateJune 2009
Estimated Primary Completion DateDecember 2008
Eligibility Criteria
Inclusion Criteria:

- Children and adolescents with symptomatic bronchial asthma despite ongoing therapy

- Age 6-14 years

- Asthma diagnosed at lease six months previously (by a special pulmonary allergologic
outpatient unit)

- Demonstration of reversibility (FEV1 increased by at least 12% after
bronchospasmolysis with a beta2 sympathomimetic). This can be determined at the
screening visit or within the previous three months.

- Patients who are either steroid-naive or who received constant doses of the following
medi¬cations within the previous four weeks:

- Beclomethasone dipropionate: up to 400 µg daily

- Fluticasone propionate: up to 200 µg daily

- Budesonide: up to 400 µg daily

- Patients who are able to reliably complete the asthma diary and perform peak flow
measurements according to instructions.

- Girls of childbearing potential must have acceptable methods of contraceptions,
including sexual abstinence.

Exclusion Criteria:

- Patients who were treated with systemic steroids within the previous 30 days

- Patients using one of the following asthma medications:

- Systemic steroids

- Nedocromil, DNCG

- Theophylline

- Ketotifen

- Systemic or long-acting beta2 sympathomimetics

- Patients who have experienced one of the following events within the previous 30
days:

- A change in asthma medication

- Pulmonary infection

- Hospitalization due to bronchial asthma or any other respiratory condition

- Patients who are currently participating in another clinical trial or have done so
within the previous 30 days.

- Patients known or expected to react hypersensitively to components of the
investigational medication

- Patients receiving Phenobarbital, Phenytoin, Rifampicin (medications that are
metabolized by Cytochrom P450

- Patients with analgetic intolerance

- Pregnant females
GenderBoth
Ages6 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesGermany

Administrative Information[ + expand ][ + ]

NCT Number NCT00721240
Other Study ID NumbersTrial No. 25.08.2005
Has Data Monitoring CommitteeNo
Information Provided ByMarien Hospital Wesel
Study SponsorMarien Hospital Wesel
CollaboratorsMerck Sharp & Dohme Corp.
Investigators Principal Investigator: ANDREA VON BERG, MD Marien Hospital Wesel; FORSCHUNGSINSTITUT ZUR PRÄVENTION VON ALLERGIEN UND ATEMWEGSERKRANKUNGEN IM KINDESALTER AN DER kLINIK FÜR KINDER UND JUGENDMEDIZIN
Verification DateJuly 2008

Locations[ + expand ][ + ]

Marien Hospital Wesel gGmbH
Wesel, NRW, Germany, 46483