Effect of Donepezil on Smoking

Smoking Clinical Trial

Official title:

The Effect of Acetylcholinesterase Inhibitors on Smoking Behavior

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01250977
• Other study ID #: UPCC 12910
• Status: Completed
• Phase: Phase 2
• Start date: January 11, 2011
• Est. completion date: December 6, 2011

Study information

• Verified date: July 2019
• Source: Abramson Cancer Center of the University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this proof-of-concept pilot study is to evaluate Donepezil HCL (Aricept) for side effects and effects on smoking behavior and performance on neurocognitive tasks in a population of dependent smokers.

Description:

Nicotine dependence is a major public health problem and currently available treatments are ineffective for the majority of smokers. Thus, there is a need to develop and test novel medications to assist smokers to quit smoking. This pilot feasibility study examined: (1) tolerability and medication adherence, and (2) the effects of donepezil versus placebo on smoking behavior and cognitive performance in non-treatment seeking smokers. We predicted that 4 weeks of donepezil would improve working memory at the highest task difficulty level and sustained attention. Because participants in this study were not trying to quit, change in smoking behavior was a secondary outcome.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 6, 2011
• Est. primary completion date: December 6, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 30 smokers ages 18-50 who have smoked at least 10 cigarettes per day for the past 6 months, will be eligible to participate. They must be able to provide informed consent.

Exclusion Criteria:

• Smoking Behavior:

1. Current enrollment or plans to enroll in a smoking cessation program, or use other smoking cessation medications in the next 2 months.

2. Provide a CO reading less than 10 ppm at medical screening.

3. Participants who roll their own cigarettes.

4. Regular use of chewing tobacco or snus.

• Alcohol/Drugs 1) History of substance abuse and/or currently receiving treatment for substance abuse (e.g. alcohol, opioids, cocaine, marijuana, or stimulants). 2) Current alcohol consumption that exceeds 25 standard drinks/week. 3) Providing a breath alcohol concentration (BrAC) reading of greater than or equal to 0.01 at medical screen, baseline, or testing sessions.

• Medical:

1. Women who are pregnant, planning a pregnancy, or lactating; all female subjects shall undergo a urine pregnancy test prior to enrollment and must agree in writing to use an approved method of contraception.

2. Lifetime history or current diagnosis of psychosis, bipolar disorder, anxiety disorder, or schizophrenia, as identified by the MINI. Individuals with a past history of depression are eligible as long as their major depression episode was more than 6 months ago.

3. Serious or unstable disease within the past 6 months i.e. heart disease, liver/kidney failure)

4. Other medical conditions such as peptic ulcer disease; beign prostatic hypertrophy or bladder outflow problems; asthma or chronic obstructive pulmonary disease.

5. BP reading of 170/100 at medical screening session.

• Medication:

1) Current use, recent discontinuation within last 14 days or planned use of the following medications:

• Any form of smoking cessation medication, i.e. Zyban, Wellbutrin, Wellbutrin SR, Chantix, nicotine replacement therapy

• Psychotropic medications (anti-psychotics, anti-depressants, anti-anxiety or anti-panic medications, mood stabilizers and stimulants)

• Current treatment with other acetylcholinesterase inhibitors (ACIs) like donepezil HCL (Aricept), tacrine, rivgastigmine and galantamine

• Anti-seizure meds, and other meds that affect the cholinergic system such as mecamylamine, atropine, succinylcholine, ketocaonazole, quinidine, bethanechol, iprapropium, bromide, dicyclomine, benztropine, carisprodol, zantac, and procardia.

2) Patients shallbe instructed to refrain from using any study prohibited drugs (note participants are allowed to take prescription medicines not in the exclusion list)throughout their participation in the study.

• Other

1. Inability to complete the baseline study procedures within thee hours and/or correctly, as determined by the PI.

2. Non-English speakers.

Related Conditions & MeSH terms

• Smoking

Intervention

Drug:
• Donepezil

• Placebo

Locations

Country	Name	City	State
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Abramson Cancer Center of the University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in True Positives on the 3-Back Level of the Letter-N-Back Neurocognitive Task at Day 28 (i.e., Week 4)	Neurocognitive task performance was assessed during baseline and each testing day (Day 7, 14, 21, and 28) using computerized tasks. Working memory was assessed with the Letter-N-back task.	Baseline and Day 28
Primary	Change From Baseline in Discriminability on the Penn Continuous Performance Neurocognitive Task at Day 28 (i.e., Week 4)	Sustained attention was assessed with the Penn Continuous Performance Task (P-CPT). The primary outcome measure was the change from Baseline in discriminability (score) on the P-CPT at Day 28. The discriminability score is the mathematical difference between the total correct (i.e., true positives and correct non-responses) and incorrect (i.e., errors of commission and omission) responses to a series of stimuli presented during the P-CPT. The unit of measure is number of correct responses less the number of incorrect responses. A higher discriminability score at a single time point indicates a better performance on the P-CPT. A positive change in discriminability score between Baseline and Day 28 indicates improved performance over time. In its purest mathematical sense, the discriminability measure is a difference of difference scores and therefore is without scale limits, that is, there are no minimum or maximum values one could theoretically obtain.	Baseline and Day 28
Secondary	Change From Baseline in Smoking Behavior (i.e., Cigarettes Per Day) at Day 28 (i.e., Week 4)	At each visit, smoking rate (i.e., cigarettes per day) was assessed using standard Timeline Followback methods. Weekly averages were computed to assess group differences in changes in smoking behavior from Baseline to Day 28.	Baseline and Day 28
Secondary	Summary Side Effect Score at Day 28 (i.e., Week 4)	A 38-item self-report measure of the side effects associated with Donepezil (e.g., nausea) was administered to all participants at observation and testing days through Day 28. For each item, side effect severity was rated on a 4-point scale (0 = not present, 1 = mild, 2 = moderate, 3 = severe). The side effect summary score from the measure collected at Day 28 was considered the dependent measure because Day 28 is when the medication reached steady state. The side effect summary score was calculated by taking the mean score (i.e., sum of all 38 items [each item rated on a scale 0-3] divided by 38) of the measure from each participant at Day 28, adding the means, and then dividing the sum of the means by the number of participants within each group. A higher summary score indicates a higher general incidence rate and severity of side effects.	Day 28