Please select the eligibility criteria that correspond to the clinical trial below.
Title: S-Adenosyl-L-Methionine (SAMe) for Smoking Abstinence
Brief Summary: Cigarette smoking is of great public health importance and is the single most important preventable cause of morbidity, mortality and excess health care costs in the United States. After a steady decline for the last 50 years, the prevalence of tobacco use in the United States has reached a plateau of approximately 21%. Currently available treatments among adults are not efficacious for all tobacco users. New pharmacologic agents thus need to be continually developed and tested.

The release of dopamine in the nucleus accumbens is one of the key components of the pleasurable and rewarding effects of nicotine. Drugs that increase monoamine neurotransmitter availability (particularly dopamine and norepinephrine) are likely to increase the reward function and thus ameliorate withdrawal symptoms. S-Adenosyl-L-Methionine (SAMe), the primary methyl donor for the central nervous system (CNS), donates methyl groups towards presynaptic synthesis of CNS monoamine neurotransmitters. By facilitating the synthesis of dopamine and norepinephrine in the brain, SAMe is likely to ameliorate the symptoms of nicotine withdrawal, thus improving tobacco abstinence rates in smokers who are trying to stop smoking. SAMe is well tolerated and is available over-the-counter.

To date, no prospective clinical trial evaluating the efficacy of SAMe for the treatment of tobacco dependence has been published. We propose to evaluate the efficacy of SAMe for increasing smoking abstinence and decreasing nicotine withdrawal symptoms in a randomized, blinded, placebo-controlled, three-arm, parallel-group, dose-ranging phase II clinical trial. Participants (N=120) will be randomly assigned to one of the three groups, and will receive an 8-week course of SAMe 800-mg per day, 1600-mg per day, or a matching placebo. This study is anticipated to provide the data needed to develop a larger randomized controlled clinical trial submitted through the R01 funding mechanism, if the results appear promising.


Options:
A: 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.
B: Inclusion Criteria:

1. Has signed the ICF and is able to read and understand the information provided in the ICF.
2. Is 21 to 65 years of age (inclusive) at screening.
3. Smokes at least 10 commercially available cigarettes per day (no brand restrictions), for the last 12 months.
4. Has an expired air CO reading of at least 10 ppm at screening.
5. Is interested in switching to an electronic cigarette.
6. Is willing and able to comply with the requirements of the study.
7. Owns a smartphone with text message and data capabilities compatible with necessary surveys.

Exclusion Criteria:

1. Is unhealthy or cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason) as judged by the Investigator or designated medical staff based on all available assessments from the screening period (e.g., safety laboratory, vital signs, physical examination, ECG, concomitant medications and medical history).
2. Has a PHQ-9 score greater than 9, or a score greater than 0 on item #9 ("Thoughts that you would be better off dead, or of hurting yourself in some way") at screening.
3. Has plans to use an FDA-approved smoking cessation product during the study.
4. Has high blood pressure (systolic \> 150 mmHg or diastolic \>95 mmHg) at screening.
5. Has body mass index (BMI) less than 15.0 kg/m2 or greater than 40.0 kg/m2.
6. Has coronary heart disease, structural cardiac disease (including, but not limited to valvular heart disease or cardiac murmurs), cardiac dysrhythmias, syncope, cardiac chest pain, or history of heart attack or heart failure.
7. Has received psychotherapy or behavioral treatments potentially impacting symptoms of depression, anxiety, or nicotine withdrawal within 30 days of screening, or during the study.
8. Is taking antidepressants, psychoactive medications (e.g. antipsychotics, benzodiazepines, hypnotics) or medications that prolong QTc.
9. Has used any of these products in the past 30 days:

   1. Illegal drugs (or if the urine drug screen is positive for cocaine, THC, amphetamines, methamphetamines, or opiates);
   2. Experimental (investigational) drugs that are unknown to participant;
   3. Chronic opiate use.
10. Has used smokeless tobacco (chewing tobacco, snuff), cigars (except for "Black \& Mild" cigars or Cigarillos), pipes, hookah, e-cigarettes, nicotine replacement therapy or other smoking cessation treatments within 14 days of screening.
11. Has a plan to use an FDA-approved quit-smoking treatment in the next 30 days.
12. Is pregnant or nursing (by self-report) or has a positive pregnancy test.
13. Enrollment requirements met.
C: Inclusion Criteria:

* Is at least 18 years of age;
* Has smoked more than 10 cigarettes/day for ≥6 months;
* Is willing to make a quit attempt;
* Is able to participate fully in all aspects of the study;
* Has been provided with, understand, and have signed the informed consent.
* Is in good health as determined by the physician investigator.

Exclusion Criteria:

* Is clinically significant levels of current depression as assessed by CESD (Score \>16) and determined by the physician; or have a life-time diagnosis of bipolar disorder, schizophrenia or dementia as determined by physician investigator;
* Has an unstable medical condition.
* Is using other tobacco product and the primary use is NOT cigarettes.
* Is currently (within the past 30-days) using antipsychotics or antidepressants;
* Is currently (within the past 30-days) using any treatments for tobacco dependence (i.e., behavioral therapy, nicotine replacement therapy, bupropion SR, clonidine, or nortriptyline);
* Is currently using another investigational drug at the time of study enrollment;
* Is currently (within the past 30 days) using an herbal product or dietary supplement for tobacco abstinence;
* Has recent history (in the past 3-months) of alcohol abuse or dependence as assessed by the CAGE questionnaire and study investigators;
* Has a recent history of drug abuse as assessed by physician interview;
* Is pregnant, lactating, or of child bearing potential, likely to become pregnant during the medication phase and not willing to use a reliable form of contraception. Reliable forms of contraception include diaphragm or condom (with spermicidal), injections, intrauterine device \[IUD\], surgical sterilization and abstinence;
* Is a history of any major cardiovascular events in the past 3-months including unstable angina, acute MI or coronary angioplasty;
* Has clinically significant acute or chronic progressive or unstable neurologic, hepatic, renal, cardiovascular, respiratory or metabolic disease;
* Is currently on medications interacting with SAMe, including but not limited to, antidepressants, MAO inhibitors, levodopa, meperidine, dextromethorphan, pentazocine and tramadol;
* Has another household member or relative participating in the study;
* Has known allergy to SAMe.
D: Inclusion Criteria:

A software program using Anatomical Therapeutical Chemical (ATC) prescription codes and International Classification of Primary Care (ICPC) diagnosis codes selected potential patients with COPD. Criteria: age \>35 years and a diagnosis recorded as COPD or as ICPC code R95/96, or a prescription of at least three times of bronchodilators (ATC code R03a/bc) and/or prescription of at least two times of inhaled anti-inflammatory medication in the past year (ATC code R03). General practitioners (GPs) had to confirm the diagnosis of the selection. Patients were eligible to participate if they met the following criteria:

* Current smoking
* Suffering from COPD according to the GP's diagnosis
* In command of the Dutch language.

Exclusion Criteria:

* Too ill
* Under control of a chest physician
* Serious physical or psychological comorbidity

Answer: C