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Repurposing Cholinesterase Inhibitors for Smoking Cessation

Phase 2
18 Years
60 Years
Open (Enrolling)
Treatment-seeking Smokers, Reporting Consumption of at Least 10 Cigarettes, Per Day for at Least the Past 6 Months

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Trial Information

Repurposing Cholinesterase Inhibitors for Smoking Cessation

Nicotine dependence is a major public health problem and currently available treatments are
ineffective for the majority of smokers. Thus, there is an urgent need to develop and test
new medications to aid in smoking cessation. Recent evidence from a genetic study of
prospective smoking cessation conducted at the CIRNA suggested smoking cessation may be
influenced by variationin acetylcholine levels. The proposed proof-of-concept study is a
randomized, double-blind, placebo-controlled, parallel arm pilot study of the effects of the
acetylcholinesterase inhibitor, galantamine (vs. placebo), on short-term abstinence among 24
treatment-seeking smokers. The primary outcome is the number of days abstinence a 7 day quit
attempt. Secondary outcomes include: smoking rate during the run-up and monitored
abstinence phase, medication adherence, side effects, cognitio, and smoking urges and other
withdrawal symptons. The pilot data generated will be used to support an NIH grant
application by a new investigatot to evaluate whether acetylcholinesterase inhibitors could
be effective smoking cessation medications.

Inclusion Criteria:

- Smokers ages 18-60, 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, and express interest in quitting smoking in the next 2 to 6 months. Using a
scale from 0 to 100, they must rate their confidence that they will make a quit
attempt in the next 6 months a 50 or higher. Following the current study,
participants will be referred to a free smoking cessation program in our Center.
Those who wish to quit sooner can be referred directly to another program.

Exclusion Criteria:

- Smoking Behavior

1. Daily use of chewing tobacco, snuff, and/or snus.

2. Current enrollment in a smoking cessation program, or use of other smoking
cessation medications in the last month or plans to do either in the next month.

3. Provide a carbon monoxide (CO) breath sample reading less than 10 parts per
million (ppm) at Medical Screening.


1. Lifetime history of substance abuse (other than nicotine) and/or currently
receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine,
stimulants, PCP, benzodiazepines, or study prohibited medications/recreational
drugs) as determined by self-report during the phone screen and/or through the
MINI during the Intake.

2. Current alcohol consumption that exceeds 25 standard drinks/week over the past 6

3. Providing a breath alcohol concentration (BrAC) reading of greater than or equal
to 0.01 at Intake, Baseline, or Testing Days.

4. A positive urine drug screen for cocaine, amphetamines, methamphetamines,
benzodiazepines, PCP, methadone, barbiturates, and opiates at the Intake,
Baseline visit, and Testing days.


1. Women who are pregnant, planning a pregnancy in the next 3 months, or lactating;
all female subjects shall undergo a urine pregnancy test at the Intake and must
agree in writing to use an approved method of contraception. Following
enrollment, pregnancy tests will be conducted at the Baseline and Testing days
for all female subjects of child-bearing potential.

2. Diagnosis of Alzheimer's Disease or dementia.

3. Current treatment of cancer or diagnosed with cancer (except basal cell
carcinoma) in the past 6 months.

4. Liver/kidney failure, peptic ulcer disease, benign prostate hypertrophy.

5. Asthma or chronic obstructive pulmonary disease (COPD).

6. History (last 6 months) of abnormal heart rhythms, tachycardia and/or
cardiovascular disease (stroke, angina, heart attack). These conditions will be
evaluated on a case by case basis by the Study Physician/Health Care Provider.

7. Serious or unstable disease within the past 6 months, as determined by the Study
Physician/Health Care Provider.

8. Clinically significant abnormalities within physical examination and vital signs
at Intake. Abnormalities will be assessed by the Study Physician/Health Care
Provider and eligibility will be determined on a case-by-case basis.

9. Any impairment (physical and/or neurological) including visual or other
impairment preventing cognitive task performance.

10. Uncontrolled high blood pressure (SBP greater than 160 or DBP greater than 100).

11. Hearing impairment, significant hearing loss (more than 20% in either ear),
cochlear implants, or bi-lateral hearing aids.

12. History of brain injury.

13. History of epilepsy or a seizure disorder.

14. Color Blindness.

15. Low or borderline intellectual functioning - determined by receiving a score of
less than 90 on the Shipley Institute of Living Scale (SILS) which correlates
with the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Estimated IQ Test
(administered at Intake).

Psychiatric Exclusion (as determined by self-report on phone screen and/or
through MINI during Intake)

1. Current diagnosis of major depression. Persons with a history of major
depression, in remission for 6 months or longer, are eligible, provided they are
not excluded based on medications (below).

2. Suicide risk score on MINI greater than 0.

3. History or current diagnosis of schizophrenia, psychosis, and/or bipolar

4. Current or past hypomanic/manic episode.

5. Current or history of a diagnosis of Attention-Deficit/Hyperactivity Disorder

1. Current use, recent discontinuation (within the last month) of any form of
smoking cessation medications (i.e., Zyban, Wellbutrin, Wellbutrin SR, Chantix,
nicotine replacement therapy);

2. Current use or recent discontinuation (within the last 60 days) of:

1. Anti-anxiety or panic disorder medications.

2. Anti-psychotic medications.

3. Mood-stabilizers (e.g., Lithium, Lamictal/lamotrigine,
Neurontin/gabapentin, Topamax/topiramate, valproic acid,

4. Anti-depressants (e.g., Wellbutrin, MAOIs, SSRIs, tricyclic

5. Prescription stimulants (e.g., Provigil, Ritalin, Adderall).

6. Systemic Steroids (e.g., Prednisone).

7. Alzheimer's disease medications (e.g., Acetylcholinesterase inhibitors
(ACIs), Aricept/donepezil, Exelon/rivastigmine, Tacrine, or memantine).

8. Parkinson's disease medications(e.g., Cogentin/benztropine).

9. Irritable bowel syndrome medication (e.g., Dicylomine/Bentyl).

10. Heart medications (e.g., quinidine or Procardia/nifedipine).

11. Peptic ulcer disease medication (e.g, Zantac/ranitidine).

12. Muscle relaxants (e.g., Soma/carisoprodol, Anectine/succinylcholine).

13. Anti-fungal medication (e.g., Nizoral/ketoconazole).

14. Anti-seizure medications (e.g., Ativan, Banzel, Carbatrol, Dilantin,
Lamictal, Gabitril, Lyrica, Neurontin, Tegretol, Topomax).

15. COPD medication (e.g., Atrovent/Ipratropium Bromide).

16. Urinary retention medications (e.g., Duvoid/bethanechol,
Proscar/finasteride, Avodart/dutasteride, Dibenzyline/phenoxybenzamine,

17. Eye medication (e.g., Atropine).

3. Daily use of:

1. Opiate-containing medications for chronic pain (e.g., Duragesic/fentanyl
patches, Percocet, Oxycontin).

2. Medication for asthma (e.g., albuterol, Serevent, Combivent, Advair,
Flovent, Azmacort, Symbicort).

4. Known allergy to study medication.

Subjects will be instructed to refrain from using any study prohibited drugs/medications
(both recreational and prescription) throughout their participation in the study. After
final eligibility is confirmed, subjects who report taking contraindicated medication(s)
over the course of the study period may only remain eligible if the Study Physician and/or
Principal Investigator determines that the contraindicated medication(s) do/did not impact
the study design, data quality, and/or subject safety/welfare. Subjects are permitted to
take necessary prescription medications not included within the exclusion list during the

General Exclusion

1. Current, anticipated, or pending enrollment in another research program over the next
2-3 months that could potentially affect subject safety and/or the study data/design
as determined by the Principal Investigator and/or Study Physician.

2. Not planning to live in the area for the next two months.

3. Any medical condition, illness, disorder, or concomitant medication that could
compromise participant safety or treatment, as determined by the Principal
Investigator and/or Study Physician.

4. Inability to provide informed consent or complete any of the study tasks as
determined by the Principal Investigator.

5. Completion of neurocognitive assessments and/or use of study medication(s) at the
CIRNA in the past 6-months that could influence performance on study tasks as
determined by the Principal Investigator.

6. Not able to effectively communicate in English (reading, writing, speaking).

7. Missing 2 or more consecutive sessions, or 3 or more sessions during the medication

8. Missing 2 or more consecutive doses during the medication period.

9. Missing 3 or more doses throughout the medication period.

Type of Study:


Study Design:

Primary Purpose: Diagnostic

Outcome Measure:

Number of Adverse Events

Outcome Time Frame:

7 days

Safety Issue:


Principal Investigator

Rebecca Ashare, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania


United States: Institutional Review Board

Study ID:

UPCC 15912



Start Date:

January 2013

Completion Date:

December 2016

Related Keywords:

  • Treatment-seeking Smokers, Reporting Consumption of at Least 10 Cigarettes
  • Per Day for at Least the Past 6 Months



Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania  19104-4283