The Effects of Memantine and Bupropion on Acute, Reinforcing, and Conditioned Effects of Cigarettes - 1

This study has been completed.
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT00136747
First received: August 25, 2005
Last updated: December 3, 2015
Last verified: December 2015
  Purpose
One of nicotine's effects on the body is at the level of the NMDA receptors in the brain. Memantine is a drug that also affects NMDA receptors, making it a candidate for the treatment of nicotine addiction. The purpose of this study is to evaluate the effectiveness of memantine using a laboratory model of tobacco addiction. The investigators will compare the effects of memantine with bupropion, medication currently used to facilitate smoking cessation.

Condition Intervention Phase
Tobacco Use Disorder
Drug: Memantine
Drug: bupropion
Drug: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Developing Medication For Tobacco Addiction: NMDA Agents

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Response to cigarette cues [ Time Frame: Days 11-13 ] [ Designated as safety issue: No ]
  • Smoking behavior [ Time Frame: Days 11-13 ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: January 2004
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BUPROPION
Participants receive 20 mg bid of memantine, placebo, or bupropion in a double-blind crossover design and are maintained on active or placebo medication for 5 or 10 days before the inpatient testing
Drug: bupropion
Experimental: placebo
Participants receive 20 mg bid of memantine, placebo, or bupropion in a double-blind crossover design and are maintained on active or placebo medication for 5 or 10 days before the inpatient testing
Drug: placebo
Experimental: memantine
Participants receive 20 mg bid of memantine, placebo, or bupropion in a double-blind crossover design and are maintained on active or placebo medication for 5 or 10 days before the inpatient testing
Drug: Memantine
Two capsules of Memantine twice daily for 12 days.

Detailed Description:

Tobacco use is the leading preventable cause of death in the United States. Recent research on the effects of nicotine on the brain and behavior presents an opportunity to advance medication development. Neurotransmission at NMDA receptors in the brain is associated with learning and memory and has been linked to many of nicotine's effects on humans. It is possible that altering NMDA neurotransmission may be helpful in treating nicotine addiction.

The goal of this study is to develop a laboratory model for early-stage testing of new and existing compounds for the treatment of tobacco and nicotine addiction. Specifically, the study will assess the effect of memantine, a non-competitive NMDA antagonist, versus bupropion, a medication currently used to facilitate smoking cessation, on various behavioral aspects related to smoking behavior, including reinforcement and cue-reactivity.

This double-blind, randomized assignment study will consist of three distinct phases (placebo, bupropion, and memantine). Each phase will include 10 days of outpatient medication maintenance, followed by 3 days of inpatient testing. During the outpatient phase, study visits will occur every 2 to 3 days. At these visits, compliance and side effects of medication will be monitored, smoking diaries will be collected, and medication will be dispensed. During the inpatient period participants will be allowed to smoke only at designated times. A variety of assessment will be conducted, including abstinence symptoms, acute effects of cigarettes, responses to cigarette cues, and cigarette self-administration.

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • DSM-IV diagnosis of nicotine dependence with psychological dependence
  • Smokes at least 15 cigarettes per day for the three months prior to enrollment
  • Currently not seeking treatment for nicotine dependence
  • Medically healthy on the basis of physical examination and medical history, vital signs, EKG, and laboratory tests
  • Females must use an effective method of contraception for the duration of the study

Exclusion Criteria:

  • DSM-IV diagnosis of abuse or dependence on alcohol or drugs other than nicotine
  • Current Axis I diagnosis or current treatment with psychotropic medications within the three months prior to enrollment
  • History of schizophrenia or other psychotic disorders, bipolar disorder, or anxiety disorders
  • Currently seeking treatment for nicotine disorders
  • On parole or probation
  • History of seizures or head trauma with loss of consciousness, brain contusion, or fracture
  • History of significant recent violent behavior
  • Blood pressure greater than 150/90
  • History of eating disorders
  • History of allergic reaction to any of the study medications
  • Pregnant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00136747

Locations
United States, New York
New York State Psychiatric Institute
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator: Adam Bisaga, M.D. New York State Psychiatric Institute
  More Information

Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT00136747     History of Changes
Other Study ID Numbers: #4725(1)  R01DA017572  R01DA017572-01  DPMC 
Study First Received: August 25, 2005
Last Updated: December 3, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by New York State Psychiatric Institute:
tobacco use

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Bupropion
Memantine
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Antiparkinson Agents
Anti-Dyskinesia Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on August 25, 2016