Clinical trial NCT01250977: Effect of Donepezil on Smoking
Official title: The Effect of Acetylcholinesterase Inhibitors on Smoking Behavior
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Smoking
Keywords: Non-treatment seeking smokers, reporting consumption of at least
10 cigarettes per day for at least the past 6 months
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2010-12-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: Baseline and Day 28
measure: Change From Baseline in Discriminability on the Penn Continuous Performance Neurocognitive Task at Day 28 (i.e., Week 4)
timeFrame: Baseline and Day 28
Secondary outcomes:
measure: Change From Baseline in Smoking Behavior (i.e., Cigarettes Per Day) at Day 28 (i.e., Week 4)
timeFrame: Baseline and Day 28
measure: Summary Side Effect Score at Day 28 (i.e., Week 4)
timeFrame: Day 28
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: Andrew Strasser, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References: