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

• ClinicalTrials.gov Identifier: NCT02420327
• Recruitment Status: Completed
• First Posted: April 17, 2015
• Results First Posted: August 17, 2018
• Last Update Posted: November 4, 2019
• Sponsor: University of Maryland, Baltimore
• Information provided by (Responsible Party): Britta Hahn, University of Maryland, Baltimore

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Basic Science Study of the Mechanisms of Attentional Enhancement by Compounds Acting on the Nicotinic Receptor	Drug: Placebo patch & placebo capsule; Drug: Placebo patch & galantamine capsule; Drug: Nicotine patch & placebo capsule; Drug: Nicotine patch and galantamine capsule	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: The Use of Low-Dose Galantamine to Potentiate the Attention-Enhancing Effects of Low-Dose Nicotine
• Study Start Date: September 2014
• Actual Primary Completion Date: March 2017
• Actual Study Completion Date: March 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Placebo patch and placebo capsule; On the double-placebo test day, participants receive a placebo patch and a placebo capsule.	Drug: Placebo patch & placebo capsule; On this test day, cognition is assessed after administration of a placebo patch and a placebo capsule.
Experimental: Nicotine patch and placebo capsule; On the nicotine test day, participants receive a nicotine patch (7 mg/24 hrs) and a placebo capsule.	Drug: Nicotine patch & placebo capsule; On this test day, cognition is assessed after administration of a nicotine patch (7 mg/24 hrs) and a placebo capsule.
Experimental: Placebo patch and galantamine capsule; On the galantamine test day, participants receive a placebo patch and a capsule containing 4 mg of galantamine.	Drug: Placebo patch & galantamine capsule; On this test day, cognition is assessed after administration of a placebo patch and a galantamine capsule (4 mg p.o.).
Experimental: Nicotine patch and galantamine capsule; 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; 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.).

Outcome Measures

Primary Outcome Measures :

1. Spatial Attentional Resource Allocation Task Predictive Trials Reaction Time [ Time Frame: 45 min ]
   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.
2. Rapid Visual Information Processing Task Hit Rate [ Time Frame: 30 min ]
   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.
3. Change Detection Task Accuracy [ Time Frame: 15 min ]

   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.

4. Spatial Attentional Resource Allocation Task (SARAT) Non-predictive Trial Reaction Time [ Time Frame: 45 min ]
   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.
5. Rapid Visual Information Processing Task Reaction Time [ Time Frame: 30 min ]
   The task requires the detection of three consecutive odd or three consecutive even digits in a stream of sequentially presented digits.
6. Change Detection Task Reaction Time [ Time Frame: 15 min ]

   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.

Secondary Outcome Measures :

1. Profile of Mood Scale - Total Mood Disturbance [ Time Frame: 5 min ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, Maryland

University of Maryland School of Medicine, Maryland Psychiatric Research Center

Catonsville, Maryland, United States, 21228

Sponsors and Collaborators

University of Maryland, Baltimore

Investigators

• Principal Investigator: Britta Hahn, Ph.D.; University of Maryland, Baltimore

  Study Documents (Full-Text)

Documents provided by Britta Hahn, University of Maryland, Baltimore:

Study Protocol and Statistical Analysis Plan  [PDF] July 3, 2018

More Information

• Responsible Party: Britta Hahn, Associate Professor, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT02420327
• Other Study ID Numbers: HP-00057097
• First Posted: April 17, 2015
• Results First Posted: August 17, 2018
• Last Update Posted: November 4, 2019
• Last Verified: October 2019

Keywords provided by Britta Hahn, University of Maryland, Baltimore:

nicotine; galantamine; attention; cognition; non-smoker

Additional relevant MeSH terms:

Galantamine; Nicotine; Ganglionic Stimulants; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinesterase Inhibitors; Enzyme Inhibitors; Parasympathomimetics; Nootropic Agents