Memory Reconsolidation Blockade as a Novel Intervention for Nicotine Dependence
Information source: Massachusetts General Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Smoking Cessation
Intervention: Propranolol (Drug); Placebo (Drug)
Phase: Phase 3
Sponsored by: Massachusetts General Hospital
Official(s) and/or principal investigator(s):
A. Eden Evins, MD, MPH, Principal Investigator, Affiliation: Massachusetts General Hospital
Smoking is the leading cause of preventable morbidity and mortality in the US. While
approximately 70% of smokers attempt to quit each year, only 5-15% maintain abstinence for
12 months, even with effective pharmacological and psychological interventions. Novel
therapies are needed for smoking cessation and relapse prevention. Previous studies show
that early post-cessation craving or urge to smoke is a powerful predictor of relapse. A
current model of the pathogenesis of addiction maintains that a substance of abuse causes a
marked increase release in phasic dopamine release, which in turn strengthens or increases
the salience of the memory of the drug experience, leading to a powerful and persistent
memory that is easily activated, leading to drug craving and often to drug use. This highly
salient memory is also implicated in the physiological arousal associated with craving
responses to smoking cues. This process is thought to be implicated in relapse to drug use
after even long periods of abstinence. Recent animal research indicates that retrieval
returns a consolidated memory such as those associated with drug craving, to a labile state
from which it must be restabilized to persist in a process termed reconsolidation. If
memories of drug-related experiences are labile when reactivated, this could represent a
window of opportunity in which the memory of drug use that underlies drug craving can be
influenced pharmacologically. Our hypothesis is that post-reactivation administration of the
B-adrenergic blocker, propranolol, following retrieval of drug-associated memories will
reduce the strength or salience of the memory by influencing reconsolidation, a process
called memory reconsolidation blockade. In this study we will test the hypothesis that a
single dose of propranolol given one hour prior to smoking-related cue exposure
(post-reactivation treatment) will decrease psychophysiological responses to smoking cues
one week later and will predict clinical response to an ensuing series of 6
post-reactivation treatments with script-driven imagery and propranolol. In order to do so,
we propose to conduct a randomized, double-blind, placebo-controlled trial of
post-reactivation treatment with propranolol in 50 adult smokers. Outcome measures will
include in physiological responses to smoking-related cues after one and six
post-reactivation treatments and smoking behavior during the treatment and during a 3-month
Official title: Memory Reconsolidation Blockade as a Novel Intervention for Nicotine Dependence
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Change in the Skin Conductance Level, Caused by Smoking Cues, Measured Using Script Driven Imagery
Change in Heart Rate (Beats Per Minute), Caused by Smoking Cues, Measured Using Script Driven Imagery
Change in the Corrugator Muscle (EMG) Level, Caused by Smoking Cues, Measured Using Script Driven Imagery
Secondary outcome: Change in Craving Level to Smoking Cues Caused by Smoking Cues, Measured Using Script Driven Imagery
1. To evaluate, in current smokers, the efficacy of a single dose of study medication
given an hour prior to smoking-related cue exposure (post-reactivation treatment) on
psychophysiological response to smoking cues one week later.
2. To evaluate, during the smoking cessation process, the clinical effect of study
medication in an ensuing series of 6 post-reactivation treatments on psychophysiologic
response to smoking cues measured one week after the last post-reactivation treatment.
3. To evaluate whether medication effect on psychophysiologic response during a single
memory reactivation session with script-driven imagery will predict clinical response
to an ensuing series of 6 post-reactivation treatments with script-driven imagery and
4. . To assess whether a single post-reactivation treatment or series of six
post-reactivation treatments is associated with reduction in self-reported craving for
cigarettes as assessed with the Tiffany QSU.
5. To assess whether a series of six post-reactivation treatments is associated with
reduction in smoking as assessed with self-report of cigarettes smoked per day and
expired air Carbon monoxide.
To achieve these aims, we will conduct a double-blind, randomized, placebo-controlled trial
in a convenience sample of 50 smokers.
Minimum age: 18 Years.
Maximum age: 65 Years.
- Healthy smokers aged 18-65 who have smoked at least 10 cigarettes/day for the past 3
- Age <18 or >65
- Systolic blood pressure <100 mm Hg;
- Medical condition that contraindicates the administration of propranolol, e. g.,
history of congestive heart failure, heart block, insulin-dependent diabetes, chronic
bronchitis, emphysema, or asthma. With regard to asthma, because many persons who
say they have had an asthma attack, especially as a child, may only have had hay
fever, another allergy, or another non-asthmatic episode, a blanket exclusion
criterion may be overly restrictive. Therefore, asthma attacks will only be
exclusionary if they a.) occurred within the past ten years, b.) occurred at any time
in life if induced by a B-blocker, or c.) are currently being treated, regardless of
the date of last occurrence. Cardiological consultation will be obtained as
- Previous adverse reaction to, or non-compliance with, a B-blocker;
- Current use of medication that may involve potentially dangerous interactions with
propranolol, including, other B-blockers, antiarrhythmics, or calcium channel
- Use of drugs of abuse other than nicotine or caffeine, such as opiates, marijuana,
cocaine, or amphetamines, as determined by saliva or urine testing;
- Pregnancy (in women of child-bearing potential, a pregnancy test will be performed)
- Current PTSD, or psychotic, melancholic, or bipolar disorder
- Diagnosis of major depressive disorder in the past 6 months or HAM-D score >15 at
- Current participation in any additional nicotine dependence treatment.
- An urgent need to stop smoking: subjects who receive placebo may not achieve optimal
smoking cessation results.
- Inability to understand the study's procedures, risks, and side effects, or to
otherwise give informed consent for participation;
- Subject candidate does not understand English
Locations and Contacts
Massachusetts General Hospital - Center For Addiction Medicine, Boston, Massachusetts 02114, United States
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Starting date: April 2008
Last updated: September 16, 2014