Low-Dose Galantamine to Potentiate the Attention-Enhancing Effects of Low-Dose Nicotine

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to test whether the attention-enhancing effects of low-dose nicotine can be enhanced by the drug galantamine, FDA-approved for the treatment of Alzheimer's disease. This proof-of-principle study is performed in healthy non-smokers and involves two single exposures to a nicotine patch (7 mg/24 hrs) and two single exposures to galantamine (4 mg). The dose of galantamine is substantially lower than the clinical dose range of 16-24 mg/day. The hypothesis is that performance-enhancing effects of nicotine are greater in the presence of this low dose of galantamine.

Detailed Description
-----------------
Healthy non-smokers will be screened for study eligibility and receive training on three different attention tasks. Over four test session, participants will then perform these tasks after receiving (1) a placebo patch and a placebo capsule, (2) a nicotine patch (7 mg/24 hrs) and a placebo capsule, (3) a placebo patch and a galantamine capsule, and (4) a nicotine patch and a galantamine capsule. The four test session are performed on separate days and take approximately 7 hours each. During the first 5 hours, the participant may read or watch TV while nicotine and/or galantamine are being absorbed. During the last two hours, the participant will perform the attention tasks on a computer. The investigators hypothesize that performance-enhancing effects of nicotine, which were documented in previous research, will be larger in the presence than in the absence of galantamine. This proof-of-concept would have implications for the development of drugs for the treatment of conditions such as Alzheimer's disease or schizophrenia.

Official Title
-----------------
The Use of Low-Dose Galantamine to Potentiate the Attention-Enhancing Effects of Low-Dose Nicotine

Conditions
-----------------
Basic Science Study of the Mechanisms of Attentional Enhancement by Compounds Acting on the Nicotinic Receptor

Intervention / Treatment
-----------------
* Drug: Placebo patch & placebo capsule
* Drug: Placebo patch & galantamine capsule
* Drug: Nicotine patch & placebo capsule
* Drug: Nicotine patch and galantamine capsule


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 21 to 55 years. No exposure to any nicotine-containing product in the last year. Smoked no more that 40 cigarettes, cigars or cigarillos in lifetime. Normal or corrected to normal vision (at least 20/80). Body weight 110-220 lbs. Exclusion Criteria: Pregnant or breast-feeding. Drug or alcohol abuse or dependence currently or in the last 2 years. DSM Axis I mood, anxiety or psychotic disorder. Cardiovascular or cerebrovascular disease, such as history of myocardial infarction and ischemia, heart failure, angina, stroke, severe arrhythmias, or EKG abnormalities (Wolf-Parkinson-White syndrome, Complete left bundle branch block, PR interval <120 ms or >200 ms, Prolonged QT interval (corrected) >500 ms, Cardiac arrhythmias as defined by PACs >3 per min or PVCs >1 per min). Uncontrolled hypertension (resting systolic BP above 140 or diastolic above 90 mm Hg). Hypotension (resting systolic BP below 90 or diastolic below 60). Significant kidney or liver impairment. Moderate to severe asthma. Obstructive pulmonary disease. Type I or II diabetes. Use of any centrally active medications; any peripherally acting cholinergic medications; cimetidine; ketoconazole; erythromycin; quinidine, or chronic nonsteroidal anti-inflammatory drugs. History of or current neurological illnesses, such as stroke, seizure disorders, neurodegenerative diseases, or organic brain syndrome. Learning disability, mental retardation, or any other condition that impedes cognition. Heart rate <55 bpm. Current or history of gastric ulcer disease. Any surgeries requiring full anesthesia scheduled within 2 weeks of any of the study test sessions. Anemia. Inability to perform the Rapid Visual Information Processing Task.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo patch and placebo capsule<br>On the double-placebo test day, participants receive a placebo patch and a placebo capsule. | Drug: Placebo patch & placebo capsule<br>* On this test day, cognition is assessed after administration of a placebo patch and a placebo capsule.<br>|
| Experimental: Nicotine patch and placebo capsule<br>On the nicotine test day, participants receive a nicotine patch (7 mg/24 hrs) and a placebo capsule. | Drug: Nicotine patch & placebo capsule<br>* On this test day, cognition is assessed after administration of a nicotine patch (7 mg/24 hrs) and a placebo capsule.<br>|
| Experimental: Placebo patch and galantamine capsule<br>On the galantamine test day, participants receive a placebo patch and a capsule containing 4 mg of galantamine. | Drug: Placebo patch & galantamine capsule<br>* On this test day, cognition is assessed after administration of a placebo patch and a galantamine capsule (4 mg p.o.).<br>|
| Experimental: Nicotine patch and galantamine capsule<br>On the nicotine + galantamine test day, participants receive a nicotine patch (7 mg/24 hrs) and a capsule containing 4 mg of galantamine. | Drug: Nicotine patch and galantamine capsule<br>* On this test day, cognition is assessed after administration of a nicotine patch (7 mg/24 hrs) and a galantamine capsule (4 mg p.o.).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spatial Attentional Resource Allocation Task Predictive Trials Reaction Time | The task requires detecting brief target stimuli presented at one of four locations in the four corner of the screen. On predictive trials, a central cue predicts the target location. | 45 min | 
| Rapid Visual Information Processing Task Hit Rate | The task requires following a stream of digits and detecting three consecutive odd or even numbers. The Hit Rate reflects the percentage of all target sequences that were detected. | 30 min | 
| Change Detection Task Accuracy | The task requires encoding the color of 1 or 5 shape items and reporting whether or not one of the items changed color. Accuracy refers to the percentage of all trials in which a correct response was given. One participant's data were excluded from this task because of excessive no-response trials. | 15 min | 
| Spatial Attentional Resource Allocation Task (SARAT) Non-predictive Trial Reaction Time | The task requires responding to brief target stimuli presented randomly in one of four locations in the four corners of the screen. On non-predictive trial, the cue does not provide any advance information about where the target will occur. | 45 min | 
| Rapid Visual Information Processing Task Reaction Time | The task requires the detection of three consecutive odd or three consecutive even digits in a stream of sequentially presented digits. | 30 min | 
| Change Detection Task Reaction Time | The task requires encoding the color of 1 or 5 shape items and reporting whether or not one of the items changed color. One participant's data were excluded from this task because of excessive no-response trials. | 15 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of Mood Scale - Total Mood Disturbance | Participants rate their current subjective state on a list of adjectives, which contribute to six factors/subscales. Total Mood Disturbance is a composite measure, obtained by summing the scores of all subscales, each with a range of 0-4, weighting the one positively valenced factor negatively. Thus, smaller or more negative values represent a more positive mood state. The theoretical range of the Total Mood Disturbance measure is from -4 to +20. | 5 min | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nicotine, galantamine, attention, cognition, non-smoker