A Pilot Study to Determine the Feasibility and Utility of Implementing of the Full Scale TOM Trial

The primary aim of the pilot (SAPS) protocol is to determine the feasibility and utility of implementing the provisional design of the full scale TOM trial (e.g., the six month treatment period, the impact of the smoking cessation intervention).

There is no active hypothesis for the Vanguard Protocol.

The protocol is a small scale pilot of the full-scale TOM trial, and it will utilize a placebo design and incorporates 4 treatment arms. In the Vanguard Protocol all participants are to complete a 4 week run-in with Advair 100/50, followed by randomization to 1 of 4 arms of study treatment. The 4 drug treatment combinations are (2 inhalers, 2 pills):

* Advair 250/50, Placebo, Placebo, Placebo
* Advair 100/50 and montelukast, Placebo, Placebo
* Advair 100/50 and theophylline, Placebo, Placebo
* Advair 100/50 and ipratropium, Placebo, Placebo The 24 week treatment phase will be followed by a 4 week washout period on Advair 100/50. There is no crossover.

Eligibility Criteria:
Inclusion Criteria:

* Gender and Age:
* Males and females, ages 18- 50

Current Smoker:

* Smoke at least 5 cigarettes per day for at least 5 years
* Positive urine cotinine test

Asthma:

* Physician diagnosed asthma
* Symptomatic, as evidenced by

  * Use of SABA two or more times per week for relief of asthma symptoms, or
  * One or more nocturnal awakenings per week for asthma symptoms ACRC - SC MEETING - 19 MAY 2012 SAPS │ 25 Confidential, not for attribution or citation.
* Pre-BD FEV1 greater than or equal to 40% predicted
* Asthma diagnosis confirmed by either

  * albuterol reversibility of FEV1 by 12% or more, or
  * 20% fall in FEV1 at 8mg or less of methacholine
* If over age 45, a DLco greater than 80% predicted
* Females of childbearing potential: not pregnant, not lactating and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study.

Exclusion Criteria:

* Diagnosis of COPD or emphysema
* Other major chronic illnesses in the opinion of the investigator that might interfere with the study:

  - e.g. including but not limited to uncontrolled diabetes, uncontrolled HIV infection or other immune system disorder, hyperthyroidism, seizure disorders, renal failure, liver disease, non-skin cancer, unstable psychiatric illness.
* Recent active substance abuse (in past 6 months)
* Lung disease other than asthma including COPD, bronchiectasis, sarcoidosis, or other significant lung disease
* Unstable cardiac disease (decompensated CHF, unstable angina, recent MI, atrial fibrillation, supraventricular or ventricular tachycardia, congenital heart disease, or severe uncontrolled hypertension).
* High risk of near fatal or fatal asthma as defined by the following 1-3

  * ICU admission of asthma in the past year
  * more than 2 hospitalizations for asthma in the previous year
  * more than 3 ED visits for asthma in the previous year
  * intubation or ICU admission for asthma in the past 2 years
  * use of more than 2 canisters of inhaled short-acting beta2-agonist in past month
* Acute asthma exacerbation in the past 4 weeks (treatment with systemic corticosteroids)