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

• ClinicalTrials.gov Identifier: NCT01926626
• Recruitment Status: Completed
• First Posted: August 21, 2013
• Results First Posted: July 29, 2015
• Last Update Posted: August 23, 2017
• Sponsor: Jed E. Rose
• Collaborators: Philip Morris USA, Inc.; National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Jed E. Rose, Duke University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Nicotine Dependence	Drug: Nicotine Patch; Drug: Moclobemide	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 76 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Moclobemide, a Reversible MAO-A Inhibitor, as an Adjunct to Nicotine Replacement Therapy in Female Smokers
• Study Start Date: September 2013
• Actual Primary Completion Date: July 2014
• Actual Study Completion Date: October 2014

Arms and Interventions

Arm

Intervention/treatment

Experimental: Nicotine Patch+Moclobemide; 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.

Drug: Nicotine Patch; Pre-Quit Period: 2 weeks of patch use (21mg/24hr) Post Quit Period: 10 weeks of patch use (21mg/24hr for 6 weeks, 14mg/24hr for 2 weeks, and 7mg/24hr for 2 weeks); Other Name: Nicoderm; Drug: Moclobemide; Pre-Quit Period: 1 week of moclobemide use (400 mg/day in 2 divided doses) Post Quit Period: 10 weeks of moclobemide use (400 mg/day in 2 divided doses); Other Name: reversible MAO-A inhibitor

Outcome Measures

Primary Outcome Measures :

1. Continuous Four-week Abstinence From Smoking [ Time Frame: Weeks 6-10 post quit day ]
   Number of participants who reported continuous four-week abstinence from smoking (weeks 6-10 post target quit date), confirmed by expired air carbon monoxide (CO).

Secondary Outcome Measures :

1. Point Abstinence From Smoking at Six Months Post Quit [ Time Frame: 7 day point abstinence from smoking at six months post quit ]
   Number of participants who reported 7-day point abstinence from smoking at six months post quit, confirmed by expired air CO.
2. Continuous Ten Week Abstinence From Smoking [ Time Frame: 10 weeks post quit day ]
   Number of participants who reported continuous ten-week abstinence from smoking (weeks 1-10 post quit day), confirmed by expired air CO.
3. Percentage of Change in Smoking Withdrawal Symptoms [ Time Frame: Quit day and 1 week, 3 weeks, 6 weeks, 10 weeks and 6 months post quit day ]
   Withdrawal symptoms will be assessed by questionnaire on Quit Day, 1 week post quit, 3 weeks post quit, 6 weeks post quit,10 weeks post quit and 6 months post quit (if applicable) using the Shiffman-Jarvik questionnaire, which consists of 33-items rated from 1 to 7, where 1= not at all, 2= very little, 3= a little, 4= moderately, 5= a lot, 6= quite a lot, and 7= extremely. The 33 items are grouped into 8 subscales: Craving, Negative Affect, Appetite, Arousal, Somatic - Anxiety, Somatic - G.I., Somatic - Respiratory Tract, and Habit Withdrawal. The range of scores for each subscale will be 1-7, with higher scores indicating more of the withdrawal symptom having been experienced.
4. Percentage of Change in Expired Air Carbon Monoxide (CO) During the First Week of Nicotine Patch Treatment. [ Time Frame: Baseline and 1 week ]
   The initial response to nicotine patch will be assessed by looking at the percent change in expired air carbon monoxide (CO) at the end of week one (Study Visit 2) relative to baseline (Study Visit 1).

Other Outcome Measures:

1. Safety of Moclobemide + Nicotine Patch [ Time Frame: 1, 2, 4, 7 and 11 weeks after starting Moclobemide + Nicotine Patch ]
   Safety of the moclobemide + nicotine patch treatment will be assessed by tabulating the number of participants rating side effects > "moderate".
2. Tolerability of Moclobemide + Nicotine Patch [ Time Frame: 1, 2, 4, 7 and 11 weeks after starting Moclobemide + Nicotine Patch ]
   Tolerability of the moclobemide + nicotine patch treatment will be assessed by tabulating the number of participants requiring dose reductions (or discontinuation of medication).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, North Carolina

Duke Center for Smoking Cessation

Charlotte, North Carolina, United States, 28210

Duke Center forSmoking Cessation

Durham, North Carolina, United States, 27705

Duke Center for Smoking Cessation

Winston-Salem, North Carolina, United States, 27103

Sponsors and Collaborators

Jed E. Rose

Philip Morris USA, Inc.

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Jed E Rose, Ph.D.; Duke University

More Information

• Responsible Party: Jed E. Rose, Professor, Department of Psychiatry and Behavioral Sciences, Duke University
• ClinicalTrials.gov Identifier: NCT01926626
• Other Study ID Numbers: Pro00044174; P50DA027840-01 ( U.S. NIH Grant/Contract )
• First Posted: August 21, 2013
• Results First Posted: July 29, 2015
• Last Update Posted: August 23, 2017
• Last Verified: August 2017

Keywords provided by Jed E. Rose, Duke University:

Nicotine addiction; Smoking Cessation; Quit Smoking; moclobemide; Nicotine Patch

Additional relevant MeSH terms:

Tobacco Use Disorder; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Moclobemide; Nicotine; Ganglionic Stimulants; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antidepressive Agents; Psychotropic Drugs; Monoamine Oxidase Inhibitors; Enzyme Inhibitors