Efficacy and Safety of Βeta-adrenoceptor Inverse Agonist and Biased Ligand, Nadolol, In Smoking Cessation of Patients With Chronic Cough With or Without Airflow Obstruction
Condition: Smoking Cessation
Intervention: Nadolol; Placebo
Intervention MeSH terms: Nadolol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 155.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      To test the hypothesis that treatment with the inverse agonist nadolol will improve smoking
      cessation in patients with chronic cough associated with long-term smoking, with or without
      airflow obstruction, including those with established chronic obstructive pulmonary disease
      (COPD) (chronic bronchitis dominant) or non-obstructive chronic bronchitis (NCB), compared to
      placebo and standard of care, while undergoing a validated smoking cessation program.
    

Eligibility criteria:

        Inclusion Criteria:

        Potential study participants will be referred from approved smoking cessation programs or
        be willing to enter a smoking cessation program administered by the participating sites.
        Individuals who meet all of the following criteria at Visit 1 are eligible for enrollment
        as study participants:

          1. Active cigarette-smoking males and females between the ages of 18-70 with chronic
             cough associated with long-term smoking, with or without airflow obstruction,
             including Non-obstructive chronic bronchitis (NCB) or physician-diagnosed COPD
             (chronic bronchitis dominant), as defined by the American Thoracic Society.

          2. Committed desire to quit smoking in conjunction with participation in an approved
             smoking cessation program administered by the participating sites. Enrollment in the
             smoking cessation program must take place prior to Visit 3 (third dose escalation
             visit).

          3. Diagnosis of COPD (chronic bronchitis dominant) or NCB, or presenting with chronic
             cough associated with long-term smoking.

          4. Pre-bronchodilator FEV1 greater than 55% of predicted

          5. Baseline blood pressure ≥ 110/65mm Hg

          6. Baseline heart rate ≥ 60 beats/min.

          7. Smoking at least 10 cigarettes per day prior to participation in the approved smoking
             cessation program.

          8. Self-reported prior failure(s) to quit smoking during participation in a smoking
             cessation program.

          9. Able to complete diary cards and comply with study procedures.

         10. Females of childbearing age may participate only if they have a negative pregnancy
             test, are non-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:

        Subjects who meet ANY of the following criteria are not eligible for enrollment:

          1. Diagnosis of asthma, cystic fibrosis, or PiZZ emphysema

          2. Inability or unwillingness to give written informed consent

          3. History of upper/lower respiratory tract infection, COPD exacerbation requiring
             systemic steroids, antibiotics, and or ER visit or urgent care within 6 weeks of Visit
             1

          4. History of adverse reaction or allergy to nadolol

          5. History of neurological, hepatic, renal, or other medical conditions that may
             interfere with the interpretation of data or the patient's participation in the study
             or may increase safety concerns

          6. History of cardiovascular diseases including uncontrolled hypertension (BP >160/100),
             ischemic heart disease, congestive heart failure (NYHA III or IV), valvular heart
             disease or cardiomyopathy

          7. Known allergy or sensitivity to atropine or ipratropium bromide

          8. Documented or self-reported current history of alcoholism or drug abuse

          9. Participation in another research trial within 30 days of starting this trial

         10. Unwillingness or inability to comply with study procedures

         11. Inability to swallow the study medication

         12. Pregnant or nursing

         13. Current use of any OTC remedies containing pseudoephedrine, ephedrine-based or
             containing dietary or herbal supplements.

         14. Scheduled for surgery requiring general anaesthesia

         15. Referred for smoking cessation without serious commitment to quit