Smoking
Conditions
Keywords
Non-treatment seeking smokers, reporting consumption of at least, 10 cigarettes per day for at least the past 6 months
Brief 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.
Detailed 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.
Interventions
DRUGDonepezil
DRUGPlacebo
Sponsors
Abramson Cancer Center at Penn Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Masking description
Double Blind
Intervention model description
This is a double-blind, human laboratory study using a between-subject design between smokers who are randomized to either donepezil HCL (Aricept®) (n=15) or placebo (n=15) for 4 weeks. Treatment randomization will be done to match both groups for age and sex.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Baseline and Day 28 | 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. |
| Change From Baseline in Discriminability on the Penn Continuous Performance Neurocognitive Task at Day 28 (i.e., Week 4) | Baseline and Day 28 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Smoking Behavior (i.e., Cigarettes Per Day) at Day 28 (i.e., Week 4) | Baseline and Day 28 | 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. |
| Summary Side Effect Score at Day 28 (i.e., Week 4) | Day 28 | 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. |
Countries
United States
Participant flow
Recruitment details
Thirty subjects were consented and screened for eligibility at an Intake Visit at the Center for Interdisciplinary Research on Nicotine Addiction (Philadelphia, PA).
Pre-assignment details
Twenty subjects ultimately completed a Baseline Visit and were randomized to receive Donepezil or Placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants are instructed to take one placebo pill every night before going to bed with a glass of water for 28 days. | 6 |
| Donepezil Participants are instructed to take one 5mg pill (donepezil HCL \[Aricept®\]) every night before going to bed with a glass of water for 28 days. | 14 |
| Total | 20 |
Baseline characteristics
| Characteristic | Placebo | Donepezil | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 14 Participants | 20 Participants |
| Age, Continuous | 35.00 years STANDARD_DEVIATION 9.58 | 33.24 years STANDARD_DEVIATION 10.51 | 33.75 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 14 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 8 Participants | 13 Participants |
| Region of Enrollment United States | 6 participants | 14 participants | 20 participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 9 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 6 | 14 / 14 |
| serious Total, serious adverse events | 0 / 6 | 0 / 14 |
Outcome results
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.
Time frame: Baseline and Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Discriminability on the Penn Continuous Performance Neurocognitive Task at Day 28 (i.e., Week 4) | -.1 correct minus incorrect responses | Standard Error 0.08 |
| Donepezil | Change From Baseline in Discriminability on the Penn Continuous Performance Neurocognitive Task at Day 28 (i.e., Week 4) | .5 correct minus incorrect responses | Standard Error 0.08 |
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.
Time frame: Baseline and Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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) | .59 True positive responses | Standard Error 0.88 |
| Donepezil | 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) | 3.4 True positive responses | Standard Error 0.88 |
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.
Time frame: Baseline and Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Smoking Behavior (i.e., Cigarettes Per Day) at Day 28 (i.e., Week 4) | 3.3 cigarettes per day | Standard Error 4.4 |
| Donepezil | Change From Baseline in Smoking Behavior (i.e., Cigarettes Per Day) at Day 28 (i.e., Week 4) | 1.9 cigarettes per day | Standard Error 1 |
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.
Time frame: Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Summary Side Effect Score at Day 28 (i.e., Week 4) | 2.3 score on a scale | Standard Error 0.7 |
| Donepezil | Summary Side Effect Score at Day 28 (i.e., Week 4) | 1.1 score on a scale | Standard Error 0.5 |