Evaluation of Moclobemide, a Reversible MAO-A Inhibitor, as an Adjunct to Nicotine Replacement Therapy in Female Smokers (RIMA)

Jed E. Rose

Status and phase: Completed; Phase 2

Conditions: Nicotine Dependence

Treatments: Drug: Nicotine Patch; Drug: Moclobemide

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT01926626

Pro00044174

P50DA027840-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The proposed study will assess the efficacy of moclobemide, a selective, reversible MAO-A inhibitor, in facilitating smoking cessation in treatment-seeking female smokers. This rationale is based on several findings from previous work: 1) cigarette smoke contains constituents that inhibit both forms of the enzyme monoamine oxidase (MAO-A and MAO-B); 2) that severity of depression symptoms after smoking abstinence is correlated with the level of MAO-A inhibition previously obtained from smoking; 3) moclobemide, an MAO-A inhibitor was found efficacious in a smoking cessation treatment trial (Berlin et al., 1995); and 4) women show a greater association between smoking and depression than men and women smokers in our previous trials report smoking to alleviate symptoms of depression to a greater extent than men.

Enrollment: 76 patients

Sex: Female

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have no known serious medical conditions;
• Female;
• Are 18-65 years old;
• Smoke an average of at least 20 cigarettes per day;
• Have smoked at least one cumulative year;
• Have a Fagerstrom Test for Nicotine Dependence score of at least 5;
• Have an expired air carbon monoxide (CO) reading of at least 10ppm;
• Able to read and understand English;
• Express a desire to quit smoking in the next thirty days.

Potential subjects must agree to avoid the following during their participation in this study:

• excessive alcohol consumption;
• use of other antidepressants;
• general anesthesia;
• participation in any other nicotine-related modification strategy outside of this protocol;
• use of tobacco products other than cigarettes, including pipe tobacco, cigars, e-cigarettes, snuff, and chewing tobacco;
• use of experimental (investigational) drugs or devices;
• use of illegal drugs;
• cimetidine;
• Tyramine rich foods;
• use of opiate medications.

Exclusion criteria

• Hypertension;

• Hypotension with symptoms;

• Coronary heart disease;

• Lifetime history of heart attack;

• Cardiac rhythm disorder;

• Chest pains;

• Cardiac (heart) disorder;

• Active skin disorder;

• Liver or kidney disorder;

• Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;

• Active ulcers in the past 30 days;

• Currently Symptomatic lung disorder/disease;

• Brain abnormality;

• Migraine headaches that occur more frequently than once per week;

• Recent, unexplained fainting spells;

• Problems giving blood samples;

• Diabetes (unless controlled by diet and exercise alone);

• Current cancer or treatment for cancer in the past six;

• Other major medical condition;

• Current psychiatric disease;

• Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide;

• Current depression;

• Bulimia or anorexia;

• Use (within the past 45 days) of psychiatric medications including antidepressants and anti-psychotics;

• Use (within the past 30 days) of:

  • Illegal drugs (or if the urine drug screen is positive for tetrahydrocannabinol (THC), Cocaine, Amphetamine, Opiates, Methamphetamines, phencyclidine (PCP), Benzodiazepines, or Barbiturates),
  • Experimental (investigational) drugs;
  • Any medications that are known to affect smoking cessation (e.g. clonidine);
  • Smokeless tobacco (chewing tobacco, snuff), pipes or e-cigarettes;
  • Wellbutrin, bupropion, Zyban, Chantix, nicotine replacement therapy or any other smoking cessation aid.

• Use of opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed) within the past 14 days;

• Smokes more than one cigar a month.

• Alcohol abuse;

• Significant adverse reaction to nicotine patches, in the past.

• Known hypersensitivity to moclobemide or other MAO-A inhibitors.

• Current participation or recent participation (in the past 30 days) in another smoking study at our center or another research facility.

• Current participation or recent participation (in the past six months) in another medical research study.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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76 participants in 1 patient group

Nicotine Patch+Moclobemide

Experimental group

Description:

After 1 week of pre-cessation nicotine patch treatment (21 mg/24 h patches), participants will receive moclobemide (400 mg/day in 2 divided doses) for 11 weeks, ending 10 weeks after the target quit date. Nicotine patch treatment will continue at 21 mg/24 h for an additional week prior to the quit date, and then for 6 weeks after the quit date, followed by 14 mg/24 h for 2 weeks and 7 mg/24 h for 2 weeks. All treatment will terminate 10 weeks after the quit date.

Treatment:

Drug: Moclobemide

Drug: Nicotine Patch