Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of a Tailored Dose of Varenicline on Post-quitting Urges to Smoke
Brief Summary: Varenicline is a partial nicotinic agonist which acts on alpha4 beta2 nicotinic receptors. It is presumed to alleviate withdrawal discomfort, but also to diminish rewarding effects of cigarettes. The standard varenicline dosing has been formulated to avoid adverse reactions (primarily nausea) in sensitive clients. The downside of this cautious approach is that a substantial proportion of clients may be under-dosed. A blanket dose increase would inevitably increase the incidence of side effects, but it is likely that tailoring varenicline dosing to clients' needs would be safe and may further increase varenicline's efficacy.

This study will recruit 200 smokers who report little change to their enjoyment of cigarettes and no nausea, during the first week of varenicline use. These smokers will be randomised to receive the standard dose plus placebo or plus individualised varenicline dose up to 5mg, titrated over the next week prior to their target quit day. Urges to smoke, and other withdrawal symptoms, experienced during the study period will be compared between groups to see if the tailored therapy may be useful.


Options:
A: Inclusion Criteria:

* Male and female cigarette smokers over the age of 18 years who are not willing/able to quit smoking within the next month but who are willing to attempt to reduce their smoking to work toward a quit attempt within the next 3 months.
* Subjects must have smoked an average of at least 10 cigarettes per day during the past year and during the month prior to the screening visit, with no continuous period of abstinence greater than 3 months in the past year and who have an exhaled carbon monoxide (CO) \>10 ppm at screening.
* Subjects with mild to moderate depression or anxiety may be included if their condition is stable.

Exclusion Criteria:

* Subjects with a history of a suicide attempt or any suicidal behavior in the past two years.
* Subjects with severe depression or anxiety.
* Subjects with psychosis, panic disorder, bipolar disorder, post traumatic stress disorder (PTSD), or schizophrenia.
* Subjects with alcohol or substance abuse or dependence (except nicotine) unless in full remission for at least 12 months.
B: Inclusion Criteria:

* 18-65 years old;
* smoked an average of at least 10 cigarettes per day for three cumulative years;
* have an expired air CO reading assessed at screening of at least 10ppm;
* express a desire to quit smoking within the next 30 days.

Exclusion Criteria:

* Hypertension (systolic \>140 mm Hg, diastolic \>100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100.
* Hypotension with symptoms (systolic \<90 mm Hg, diastolic \<60 mm Hg).
* Coronary heart disease;
* Lifetime history of heart attack;
* Cardiac rhythm disorder (irregular heart rhythm);
* Chest pains (unless history, exam, and ECG clearly indicate a non-cardiac source);
* Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure);
* History of skin allergy;
* Active skin disorder (e.g., psoriasis) within the last five years, except minor skin conditions (including but not limited to facial acne, minor localized infections, and superficial minor wounds);
* Liver or kidney disorder (except kidney stones, gallstones);
* Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;
* Active ulcers in the past 30 days;
* Currently symptomatic lung disorder/disease (including but not limited to chronic obstructive pulmonary disease (COPD), emphysema, and asthma);
* Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder);
* Migraine headaches that occur more frequently than once per week;
* Recent, unexplained fainting spells;
* Problems giving blood samples;
* Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less than 180mg/dcl and HbA1c is less than 7%);
* Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);
* Other major medical condition;
* Current psychiatric disease (with the exception of anxiety disorders, obsessive compulsive disorder (OCD) and ADHD);
* Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide;
* Current depression;
* Bulimia or anorexia;
* Pregnant or nursing mothers;
* Alcohol abuse;
* Use of Opiate medications for pain or sleep in the past 14 days;
* Significant adverse reaction to nicotine patches, nicotine inhalers, bupropion / Wellbutrin / Zyban or Chantix / Varenicline in the past.
* Use (within the past 30 days) of:
* Illegal drugs (or if the urine drug screen is positive),
* Experimental (investigational) drugs;
* Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine);
* Smokeless tobacco (chewing tobacco, snuff), cigars, pipes or e-cigarettes;
* Wellbutrin, bupropion, Zyban, Chantix, nicotine replacement therapy or any other smoking cessation aid.
C: Inclusion Criteria:

* Smoker seeking treatment
* Aged 18 and over
* Consenting to take part
* Report little or no change in enjoyment of cigarettes and/or nausea

Exclusion Criteria:

* Pregnant or breastfeeding
* Have severe kidney disease
* Have severe heart problems
* Have a current psychiatric illness
* Are unable to fill in questionnaires in English
* Have an allergy to varenicline
* Are currently involved in another clinical trial
D: Inclusion Criteria:

* Informed Consent as documented by signature
* Persons aged 18 or older
* Currently smoking 5 or more cigarettes a day for at least 12 months
* Willing to try to quit smoking within the next 3 months,
* Persons providing a valid phone number, a valid email address and/or a valid postal address.

Exclusion Criteria:

* Known hypersensitivity or allergy to contents of the e-liquid
* Participation in another study with investigational drug within the 30 days preceding the baseline visit and during the present study where interactions are to be expected
* Women who are pregnant or breast feeding
* Intention to become pregnant during the course of the scheduled study intervention, i.e. within the first 6-months of the study
* Persons having used ENDS regularly in the 3 months preceding the baseline visit
* Persons having used nicotine replacement therapy (NRT) or other medications with demonstrated efficacy as an aid for smoking cessation such as varenicline or bupropion within the 3 months preceding the baseline visit
* Persons who cannot attend the 6- month follow-up visit for any reason
* Cannot understand instructions delivered in person or by phone, or otherwise unable to participate in study procedures

Answer: C