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.