Effect of Donepezil on Smoking

• Sponsor: Abramson Cancer Center of the University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01250977
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Actual Duration (Months): 10.8
• Patients Per Site Per Month: 2.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Smoking	Drug: Donepezil; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.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.
• Masking: Double (Participant, Investigator)
• Masking Description: Double Blind
• Primary Purpose: Supportive Care
• Official Title: The Effect of Acetylcholinesterase Inhibitors on Smoking Behavior
• Actual Study Start Date: Jan 11, 2011
• Actual Primary Completion Date: Dec 6, 2011
• Actual Study Completion Date: Dec 6, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants are instructed to take one placebo pill every night before going to bed with a glass of water for 28 days.	Drug: Placebo
Experimental: 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.	Drug: Donepezil; Other Names: Aricept

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts 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.

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Abramson Cancer Center of the University of Pennsylvania

Investigators

• Principal Investigator: Andrew Strasser, MBBS, PhD, Abramson Cancer Center of the University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abramson Cancer Center of the University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01250977
• Other Study ID Numbers: UPCC 12910
• First Posted: Dec 1, 2010
• Last Update Posted: Jul 11, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Abramson Cancer Center of the University of Pennsylvania: Non-treatment seeking smokers, reporting consumption of at least; 10 cigarettes per day for at least the past 6 months
• Additional relevant MeSH terms: Donepezil

Study Results

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 Detail	Twenty subjects ultimately completed a Baseline Visit and were randomized to receive Donepezil or Placebo.

Arm/Group Title	Placebo	Donepezil
Arm/Group Description	Participants are instructed to take one placebo pill every night before going to bed with a glass of water for 28 days.	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.
Period Title: Overall Study
STARTED	6	14
COMPLETED	6	12
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Placebo	Donepezil	Total
Arm/Group Description	Participants are instructed to take one placebo pill every night before going to bed with a glass of water for 28 days.	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.	Total of all reporting groups
Overall Participants	6	14	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	14 100%	20 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.00 (9.58)	33.24 (10.51)	33.75 (9.90)
Sex: Female, Male (Count of Participants)
Female	2 33.3%	5 35.7%	7 35%
Male	4 66.7%	9 64.3%	13 65%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	6 100%	14 100%	20 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 7.1%	1 5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	5 35.7%	5 25%
White	5 83.3%	8 57.1%	13 65%
More than one race	1 16.7%	0 0%	1 5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%	14 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Donepezil
Arm/Group Description	Participants are instructed to take one placebo pill every night before going to bed with a glass of water for 28 days.	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.
Measure Participants	6	12
Mean (Standard Error) [True positive responses]	.59 (.88)	3.4 (.88)

2. Primary Outcome

Title	Change From Baseline in Discriminability on the Penn Continuous Performance Neurocognitive Task at Day 28 (i.e., Week 4)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Donepezil
Arm/Group Description	Participants are instructed to take one placebo pill every night before going to bed with a glass of water for 28 days.	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.
Measure Participants	6	12
Mean (Standard Error) [correct minus incorrect responses]	-.1 (.08)	.5 (.08)

3. Secondary Outcome

Title	Change From Baseline in Smoking Behavior (i.e., Cigarettes Per Day) at Day 28 (i.e., Week 4)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Donepezil
Arm/Group Description	Participants are instructed to take one placebo pill every night before going to bed with a glass of water for 28 days.	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.
Measure Participants	6	12
Mean (Standard Error) [cigarettes per day]	3.3 (4.4)	1.9 (1.0)

4. Secondary Outcome

Title	Summary Side Effect Score at Day 28 (i.e., Week 4)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Donepezil
Arm/Group Description	Participants are instructed to take one placebo pill every night before going to bed with a glass of water for 28 days.	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.
Measure Participants	6	12
Mean (Standard Error) [score on a scale]	2.3 (.7)	1.1 (.5)

Adverse Events

Time Frame	Adverse event data were collected over a 28-day period.
Adverse Event Reporting Description	The safety population described within this section includes all subjects who received at least one dose of Donepezil or Placebo. Systematic Assessment: Side effect severity was rated on a 4-point scale (0 = not present, 1 = mild, 2 = moderate, 3 = severe) using a 38-item self-report measure based on common side effects of Donepezil (e.g., nausea) at all in-person visits (n=9).
Arm/Group Title	Placebo		Donepezil
Arm/Group Description	Participants are instructed to take one placebo pill every night before going to bed with a glass of water for 28 days.		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.
All Cause Mortality
	Placebo		Donepezil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Donepezil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Donepezil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)		14/14 (100%)
Cardiac disorders
Chest Pain	1/6 (16.7%)	1	2/14 (14.3%)	3
Eye disorders
Abnormal Vision	0/6 (0%)	0	1/14 (7.1%)	3
Eye Redness/Irritation	1/6 (16.7%)	1	4/14 (28.6%)	10
Gastrointestinal disorders
Nausea	0/6 (0%)	0	3/14 (21.4%)	10
Diarrhea	0/6 (0%)	0	4/14 (28.6%)	8
Vomiting	0/6 (0%)	0	1/14 (7.1%)	1
Abdominal pain or bloating	1/6 (16.7%)	1	2/14 (14.3%)	3
Flatulence	0/6 (0%)	0	2/14 (14.3%)	3
Black Stool	0/6 (0%)	0	1/14 (7.1%)	1
General disorders
Fatigue or tiredness	4/6 (66.7%)	14	6/14 (42.9%)	13
Decreased Appetite	0/6 (0%)	0	6/14 (42.9%)	10
Weight Decrease	0/6 (0%)	0	3/14 (21.4%)	6
Dizziness	2/6 (33.3%)	4	3/14 (21.4%)	7
Drowsiness	3/6 (50%)	15	7/14 (50%)	11
Dehydration	2/6 (33.3%)	8	3/14 (21.4%)	6
Fever	0/6 (0%)	0	2/14 (14.3%)	3
Hot Flashes	0/6 (0%)	0	1/14 (7.1%)	4
Musculoskeletal and connective tissue disorders
Muscle Cramps	1/6 (16.7%)	1	1/14 (7.1%)	3
Body Pain (including Back Pain)	1/6 (16.7%)	3	3/14 (21.4%)	7
Joint Pain	0/6 (0%)	0	3/14 (21.4%)	14
Nervous system disorders
Headache	3/6 (50%)	16	5/14 (35.7%)	17
Psychiatric disorders
Insomnia	2/6 (33.3%)	10	4/14 (28.6%)	10
Depressed Mood	1/6 (16.7%)	1	1/14 (7.1%)	4
Abnormal Dreams	3/6 (50%)	9	8/14 (57.1%)	21
Hostility	0/6 (0%)	0	1/14 (7.1%)	3
Nervousness	1/6 (16.7%)	6	1/14 (7.1%)	4
Confusion	1/6 (16.7%)	1	2/14 (14.3%)	5
Renal and urinary disorders
Frequent Urination	0/6 (0%)	0	4/14 (28.6%)	7
Incontinence	0/6 (0%)	0	1/14 (7.1%)	4
Difficulty Urinating	0/6 (0%)	0	1/14 (7.1%)	2
Respiratory, thoracic and mediastinal disorders
Cough	4/6 (66.7%)	12	6/14 (42.9%)	18
Sore Throat	4/6 (66.7%)	5	5/14 (35.7%)	14
Skin and subcutaneous tissue disorders
Large Bruises	0/6 (0%)	0	1/14 (7.1%)	1
Itching	0/6 (0%)	0	2/14 (14.3%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.