Colchicine in Moderate Asthma (CIMA) Trial
Objectives:
Because colchicine is an anti-inflammatory agent, an
examination of its potential efficacy in asthma is best carried out in a
population of subjects whose disease is thought to have a significant and yet
remediable chronic inflammatory component. Unfortunately, there is no specific
test that identifies such patients. However, it is reasonable to assume that
patients who use inhaled corticosteroids for control of symptoms and lung
function are suitable for such a study. Thus, the following hypothesis is
proposed: In patients with moderate asthma who use inhaled corticosteroids for
control of symptoms and lung function, colchicine provides therapeutic benefit
as measured by maintenance of control when inhaled steroids are discontinued.
Background:
Population studies indicate that the majority of
asthmatics have mild to moderate disease requiring use of medications for
control of symptoms. A significant but unknown fraction of these patients use
inhaled corticosteroids for control. Although regular use of inhaled steroids
is now considered standard therapy for such patients, the risks of long term
use of such agents are unknown, especially in younger individuals still in
growth stages of development and in post-menopausal women who are at risk for
accelerated bone density loss. If colchicine furnishes an additional measure of
control without side effects to patients on chronic inhaled steroid therapy, it
may have a significant impact on asthma morbidity in a large number of
patients. Such a finding would warrant further investigation of colchicine's
efficacy in patients with severe asthma who, despite chronic oral
corticosteroid therapy, continue to experience considerable disability,
frequent hospitalizations, and significant morbidity from the disease as well
as its treatment. If colchicine maintains control during inhaled steroid
withdrawal, it will represent a useful alternative to inhaled steroids with
cost advantages as well as possible advantages in terms of toxicity with long
term therapy.
Subjects:
This trial will examine the safety and efficacy of
oral colchicine in 70 patients with asthma of moderate severity who use inhaled
corticosteroids for control of symptoms. For entry, patients must use 336 mcgs
daily but not more than 1600 mcg daily of any inhaled corticosteroid (e.g.,
triamcinolone acetonide, beclomethasone dipropionate, or fluonisolide) for
symptom control. Patients should be on daily inhaled steroids at a stable dose
in the above range for at least 30 days prior to entry and should have a
baseline FEV1 between 55-90% predicted.
Design:
During a 4-week run-in phase, patients will be
stabilized on triamcinolone acetonide at a dose of 4 puffs twice daily, or 800
mcg daily, and asthma control will be assessed by peak flow rates (AM &
PM), asthma symptom scores, as needed inhaled beta-agonist use, airway
responsiveness, spirometry, quality of life measures, and episodes of adverse
asthma control. For the last two weeks of the run-in period all patients will
receive colchicine (0.6 mg, twice daily), in addition to the inhaled
corticosteroid, in order to assess their tolerance of colchicine. Patients
unable to tolerate colchicine or to maintain FEV1 55% predicted at the end of
the run-in phase will be dropped from the study.
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Study Website |
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Study Documentation |
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Data Distribution Agreement |
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