Trial Outcomes & Findings for Memory Reconsolidation Blockade as a Novel Intervention for Nicotine Dependence (NCT NCT00916721)

Results Overview

Skin conductance level was obtained through 9-mm (sensor diameter) Ag/AgCl electrodes filled with isotonic paste placed on the non-dominant hypothenar surface using a constant-voltage technique. A Coulbourn Modular Instrument System was used to measure SC during 4 periods; baseline, reading, imagery and recovery.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

113 participants

Primary outcome timeframe

skin conductance was measured at visit 3, after presentation of two neutral and two smoking scripts

Results posted on

2014-09-19

Participant Flow

Treatment seeking adults smokers were enrolled from May 2008 to March 2010 at the Center for Addiction Medicine of the Massachusetts General Hospital, in compliance with the Declaration of Helsinki, the U.S. Food and Drug Administration guidelines, and the International Conference on Harmonization Good Clinical Practices Guidelines.

39 were excluded before randomization: Did not meet inclusion criteria (21),Declined to participate (18) Three participants were discontinued before receiving study medication: due to bradycardia (1), cocaine use (1), recent use of albuterol (1)

Participant milestones

Participant milestones
Measure	Propranolol A single oral dose of propranolol or identical placebo capsule in a double-blind fashion. Propranolol dose was 0.67 mg/kg of the short-acting formulation, rounded to the nearest 10 mg, with a minimum dose of 40 mg and a maximum dose of 80 mg	Placebo A single oral dose of identical placebo capsule in a double-blind fashion
Overall Study STARTED	35	39
Overall Study COMPLETED	25	29
Overall Study NOT COMPLETED	10	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Propranolol A single oral dose of propranolol or identical placebo capsule in a double-blind fashion. Propranolol dose was 0.67 mg/kg of the short-acting formulation, rounded to the nearest 10 mg, with a minimum dose of 40 mg and a maximum dose of 80 mg	Placebo A single oral dose of identical placebo capsule in a double-blind fashion
Overall Study Lost to Follow-up	0	1
Overall Study Adverse Event	6	3
Overall Study Withdrawal by Subject	2	2
Overall Study Protocol Violation	2	4

Baseline Characteristics

Memory Reconsolidation Blockade as a Novel Intervention for Nicotine Dependence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Propranolol n=35 Participants	Placebo n=39 Participants	Total n=74 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	35 Participants n=93 Participants	39 Participants n=4 Participants	74 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	41.6 years STANDARD_DEVIATION 10.9 • n=93 Participants	42.5 years STANDARD_DEVIATION 9.84 • n=4 Participants	42.1 years STANDARD_DEVIATION 10.23 • n=27 Participants
Sex: Female, Male Female	8 Participants n=93 Participants	12 Participants n=4 Participants	20 Participants n=27 Participants
Sex: Female, Male Male	27 Participants n=93 Participants	27 Participants n=4 Participants	54 Participants n=27 Participants
Region of Enrollment United States	35 participants n=93 Participants	39 participants n=4 Participants	74 participants n=27 Participants

PRIMARY outcome

Timeframe: skin conductance was measured at visit 3, after presentation of two neutral and two smoking scripts

Skin conductance level was obtained through 9-mm (sensor diameter) Ag/AgCl electrodes filled with isotonic paste placed on the non-dominant hypothenar surface using a constant-voltage technique. A Coulbourn Modular Instrument System was used to measure SC during 4 periods; baseline, reading, imagery and recovery.

Outcome measures

Outcome measures
Measure	Propranolol n=25 Participants	Placebo n=29 Participants
Change in the Skin Conductance Level, Caused by Smoking Cues, Measured Using Script Driven Imagery	0.107 µS Standard Deviation 0.728	-0.040 µS Standard Deviation 0.337

PRIMARY outcome

Timeframe: Heart rate was measured at visit 3, after presentation of two neutral and two smoking scripts

Heart rate was measured through 9-mm (sensor diameter) Ag/AgCl electrodes filled with electrolytic paste and placed on the medial surface of each forearm. Amplified electrocardiogram signal will input to a tachometer that will provide a voltage output reflecting interbeat interval, which will be transformed to HR. A Coulbourn Modular Instrument System was used to measure HR during 4 periods; baseline, reading, imagery and recovery

Outcome measures

Outcome measures
Measure	Propranolol n=25 Participants	Placebo n=29 Participants
Change in Heart Rate (Beats Per Minute), Caused by Smoking Cues, Measured Using Script Driven Imagery	0.877 beats per minute Standard Deviation 2.285	1.162 beats per minute Standard Deviation 2.064

PRIMARY outcome

Timeframe: Corrugator EMG level was measured at visit 3, after presentation of two neutral and two smoking scripts

Corrugator EMG will be obtained through Ag/AgCl electrodes. The amplified EMG signal will be integrated using a 300-msec. time constant. A Coulbourn Modular Instrument System was used to measure corrugator EMG during 4 periods; baseline, reading, imagery and recovery

Outcome measures

Outcome measures
Measure	Propranolol n=25 Participants	Placebo n=29 Participants
Change in the Corrugator Muscle (EMG) Level, Caused by Smoking Cues, Measured Using Script Driven Imagery	0.479 µV Standard Deviation 1.309	1.464 µV Standard Deviation 3.394

SECONDARY outcome

Timeframe: Craving level was measured at visit 3, after presentation of two neutral and two smoking scripts

Craving level will be measured using a 8 point Visual Analogue Scale (VAS) of craving. Participants will be ask "How much do you want a cigarette right now" Participants will answer accordingly: 0=no desire at all; 7=unable to resist craving

Outcome measures

Outcome measures
Measure	Propranolol n=25 Participants	Placebo n=29 Participants
Change in Craving Level to Smoking Cues Caused by Smoking Cues, Measured Using Script Driven Imagery	5.52 units on a scale Standard Deviation 1.1	4.3 units on a scale Standard Deviation 2.1

Adverse Events

Propranolol

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Propranolol n=35 participants at risk	Placebo n=39 participants at risk
Psychiatric disorders major depressive episode and worsen anxiety	2.9% 1/35 • Number of events 1	0.00% 0/39

Other adverse events

Other adverse events
Measure	Propranolol n=35 participants at risk	Placebo n=39 participants at risk
Vascular disorders bradycardia	17.1% 6/35 • Number of events 6	0.00% 0/39

Additional Information

A. Eden Evins, MD, MPH, Director Center for Addiction Medicine

Massachusetts General Hospital

Phone: 617-643-4679

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place