Galantamine Effects on Nicotine Responses in Smokers

This will be a 2-4 week double-blind, placebo-controlled study. Twenty four male and female smokers will first have two 4-day treatment periods, in which they will be randomized to galantamine (8 mg/day) or placebo. These treatment periods will be separated by a 3 to 14 day washout period. During the first 3-days of each treatment period, smokers will have daily clinic visits, where they will receive study medications and any adverse effects from study medications will be monitored. Starting at 10 p.m. on Day 1 of each treatment period, subjects will refrain from smoking for approximately 2.5 days, until the experimental session on Day 4. Compliance with non-smoking will be verified by CO levels < 10 ppm. During the experimental sessions, subjects will receive saline or 1.0 mg/70 kg of nicotine intravenously in a random, double-blind manner. The sequence of nicotine treatments will be counterbalanced among subjects such that equal number of subjects will receive saline first or nicotine first. Following each saline and nicotine treatments, physiological, subjective and cognitive measurements will be obtained

Study Overview

• Status: Completed
• Conditions: Smoking; Tobacco Withdrawal
• Intervention / Treatment: Drug: Galantamine; Drug: IV Nicotine

Detailed Description

In this double-blind, crossover study, the investigators are proposing to evaluate galantamine's effects on the subjective nicotine effects and the severity of tobacco withdrawal symptoms. Twenty four male and female smokers will first have two 4-day treatment periods, in which subjects will be randomized to galantamine (8 mg/day) or placebo. These treatment periods will be separated by a 3 to 14 day washout period. This range of washout period, while minimizing carryover medication effects between treatments, will provide flexibility for subjects to comply with study procedures. During study participation, subjects will be instructed to continue to smoke as usual during the study except the 2.5 days of smoking abstinence before each test session. Starting at 10 p.m. on Day 1 of each treatment period, subjects will refrain from smoking for approximately 2.5 days, until the test session on Day 4. Subjects will have twice daily outpatient visits during the first 3 days and a test session on day 4. During the outpatient visits, study medication will be administered and tobacco withdrawal symptoms and compliance with smoking abstinence will be monitored. On Day 4 of each treatment phase subjects will have a test session, where they will receive saline or 1.0 mg/70 kg of nicotine intravenously in a random, double-blind manner. The sequence of nicotine treatments will be counterbalanced among subjects such that equal number of subjects will receive saline first or nicotine first. Following each saline and nicotine administration, physiological, subjective and cognitive measurements will be obtained.

Currently 12 subjects completed this protocol. This study is in data analysis. (April 2011)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Department of Veterans Affairs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• female and male smokers, aged 18 to 55 years;
• history of smoking daily for the past 12 months, at least 15 cigarettes daily;
• CO level > 10ppm;
• for women: not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.

Exclusion criteria:

• history of major medical illnesses including asthma or chronic obstructive lung disease, history or current gastrointestinal ulcer, hepatic or renal impairment and cardiac rhythm disturbances or other medical conditions that the study physician deems contraindicated for the subject to be in the study;
• regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics) and/or recent psychiatric diagnosis and treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia and panic disorder within the past year;
• current dependence on alcohol or on drugs or treatments for drug or alcohol addiction ;
• use of drugs that slow heart rate (eg, beta-blockers), which may increase the risk of bradycardia and AV block, or NSAIDs, which may increase potential for developing ulcers/active or occult gastrointestinal bleeding;
• known allergy to galantamine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Galantamine; galantamine will be given with intravenous nicotine	Drug: Galantamine; 8mg/a day or placebo; Other Names: Razadyne, Razadyne ER
Experimental: Nicotine; Subject will be given IV Nicotine	Drug: IV Nicotine; 1.0 mg/70 kg of nicotine against saline; Other Names: liquid nicotine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Galantamine Effects on Nicotine Responses in Smokers	Urine sample and blood samples anticipated for 24 male and females	1 year to complete

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D., Yale University

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: April 5, 2011
• First Submitted That Met QC Criteria: August 12, 2011
• First Posted (Estimate): August 16, 2011

Study Record Updates

• Last Update Posted (Estimate): July 8, 2015
• Last Update Submitted That Met QC Criteria: July 7, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: nicotine; galantamine; subjective nicotine; tobacco withdrawal symptoms
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nootropic Agents; Cholinesterase Inhibitors; Parasympathomimetics; Nicotine; Galantamine
• Other Study ID Numbers: HIC1001006227; NCT01417429 (Registry Identifier: Clinical trials)