Influence of Escitalopram on Fear Conditioning

• ClinicalTrials.gov Identifier: NCT01398514
• Recruitment Status: Completed
• First Posted: July 20, 2011
• Results First Posted: September 27, 2013
• Last Update Posted: June 11, 2014
• Sponsor: Massachusetts General Hospital
• Collaborator: Forest Laboratories
• Information provided by (Responsible Party): Naomi M. Simon, Massachusetts General Hospital

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Basic Science
• Condition: Fear Conditioning
• Intervention: Drug: Escitalopram
• Enrollment: 65

Participant Flow

Recruitment Details	Participants free of DSM-IV Axis I disorders with varying levels of subsyndromal anxiety were recruited by advertisements (e.g., postings on Craigslist, postings on Massachusetts General Hospital research participation registry) from March 2009 through April 2011.
Pre-assignment Details	65 participants signed consent and were screened for enrollment. 10 participants did not meet study entry criteria due to exclusionary psychiatric conditions. Of the 55 eligible participants, 3 withdrew and 1 was lost to follow up. 52 participants were randomly assigned to a treatment arm. Fourteen were excluded from analyses.

Arm/Group Title	Active Medication	Placebo
Arm/Group Description	Escitalopram 10mg/day	Matched pill placebo
Period Title: Overall Study
Started	26	26
Completed	18	20
Not Completed	8	6
Reason Not Completed
Adverse Event	1	0
Non-compliance with study procedures	2	0
Physiologic non-responsiveness	1	3
Failure to show a conditioned response	4	3

Baseline Characteristics

Arm/Group Title		Active Medication	Placebo	Total
Arm/Group Description		Escitalopram 10mg/day	Matched pill placebo	Total of all reporting groups
Overall Number of Baseline Participants		26	26	52
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants	26 participants	52 participants
	<=18 years	1 3.8%	0 0.0%	1 1.9%
	Between 18 and 65 years	25 96.2%	26 100.0%	51 98.1%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	26 participants	26 participants	52 participants
		34.04 (11.56)	30.46 (11.46)	32.25 (11.54)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants	26 participants	52 participants
	Female	14 53.8%	12 46.2%	26 50.0%
	Male	12 46.2%	14 53.8%	26 50.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	26 participants	26 participants	52 participants
		26	26	52

Outcome Measures

1. Primary Outcome

Title	Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Early Extinction Trials 1 to 4
Description	Three-way interaction between group (active vs. placebo), CS (+ vs. -), and trials (1 - 4). CS+ refers to the conditioned stimulus associated with the unconditioned stimulus (electric shock). Higher numbers reflect higher skin conductance response to the CS+ (conditioned stimulus). CS- refers to the stimulus not associated with the unconditioned stimulus. Higher numbers reflect higher skin conductance response to a CS-. Square-root transformed skin conductance conditioned response are reported for trials 1 to 4 of the Early Extinction Phase.
Time Frame	Day 2 of Fear Conditioning Paradigm (15 to 18 days post medication initiation)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Medication CS-	Active Medication CS+	Placebo CS-	Placebo CS+
Arm/Group Description:	Escitalopram 10mg/day	Matched pill placebo	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	16	16	18	18
Mean (Standard Error); Unit of Measure: micro-Siemens (square rooted)
Trial 1	0.745 (0.130)	0.853 (0.853)	0.799 (0.122)	0.717 (0.123)
Trial 2	0.496 (0.103)	0.634 (0.114)	0.386 (0.097)	0.558 (0.108)
Trial 3	0.544 (0.111)	0.520 (0.124)	0.438 (0.105)	0.787 (0.117)
Trial 4	0.374 (0.110)	0.361 (0.116)	0.309 (0.104)	0.510 (0.109)

2. Primary Outcome

Title	Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Acquisition Trials 1 to 5
Description	Three-way interaction between group (active vs. placebo), CS (+ vs. -), and trials (1 - 5). CS+ refers to the conditioned stimulus associated with the unconditioned stimulus (electric shock). Higher numbers reflect higher skin conductance response to the CS+ (conditioned stimulus). CS- refers to the stimulus not associated with the unconditioned stimulus. Higher numbers reflect higher skin conductance response to a CS-. Square-root transformed skin conductance conditioned response are reported for trials 1 to 5 of the Acquisition Phase.
Time Frame	Baseline on Day 1 of Fear Conditioning Paradigm (14 to 17 days post medication initiation)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Medication CS-	Active Medication CS+	Placebo CS-	Placebo CS+
Arm/Group Description:	Escitalopram 10mg/day	Matched pill placebo	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	18	18	20	20
Mean (Standard Error); Unit of Measure: micro-Siemens (square rooted)
Trial 1	0.634 (0.093)	0.574 (0.111)	0.532 (0.088)	0.634 (0.105)
Trial 2	0.419 (0.122)	0.870 (0.113)	0.428 (0.116)	0.817 (0.107)
Trial 3	0.230 (0.119)	0.685 (0.104)	0.331 (0.112)	0.856 (0.099)
Trial 4	0.231 (0.086)	0.626 (0.102)	0.181 (0.082)	0.677 (0.096)
Trial 5	0.281 (0.071)	0.543 (0.118)	0.144 (0.067)	0.714 (0.112)

Adverse Events

Time Frame	AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation.
Adverse Event Reporting Description	AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject’s participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Arm/Group Title	Active Medication		Placebo
Arm/Group Description	Escitalopram 10mg/day		Matched pill placebo
All-Cause Mortality
	Active Medication		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Active Medication		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0.00%)		0/26 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Active Medication		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/25 (52.00%)		7/26 (26.92%)
Gastrointestinal disorders
Appetite decrease † 1	2/25 (8.00%)	2	0/26 (0.00%)	0
Constipation † 1	1/25 (4.00%)	1	0/26 (0.00%)	0
Diarrhea † 1	0/25 (0.00%)	0	1/26 (3.85%)	1
Weightloss † 1	1/25 (4.00%)	1	0/26 (0.00%)	0
Dry Mouth † 1	1/25 (4.00%)	1	0/26 (0.00%)	0
General disorders
Vivid or Disturbing Dreams † 1	1/25 (4.00%)	1	1/26 (3.85%)	1
Fatigue † 1	1/25 (4.00%)	1	0/26 (0.00%)	0
Sedation / Drowsiness † 1	3/25 (12.00%)	3	0/26 (0.00%)	0
Insomnia † 1	3/25 (12.00%)	3	0/26 (0.00%)	0
Sweating / Hot Flashes † 1	1/25 (4.00%)	1	0/26 (0.00%)	0
Head cold * 1	0/25 (0.00%)	0	1/26 (3.85%)	1
Nervous system disorders
Tremor / Shakiness † 1	1/25 (4.00%)	1	0/26 (0.00%)	0
Jitteriness / Restlessness † 1	1/25 (4.00%)	1	2/26 (7.69%)	2
Headache † 1	3/25 (12.00%)	3	1/26 (3.85%)	1
Lightheadedness * 1	0/25 (0.00%)	0	1/26 (3.85%)	1
Muscle cramping / spasm † 1	0/25 (0.00%)	0	1/26 (3.85%)	1
Psychiatric disorders
Anxiety / Nervousness † 1	2/25 (8.00%)	2	0/26 (0.00%)	0
Difficulty Concentrating † 1	1/25 (4.00%)	1	0/26 (0.00%)	0
Irritability † 1	0/25 (0.00%)	0	1/26 (3.85%)	1
Reproductive system and breast disorders
Sexual Dysfunction † 1	2/25 (8.00%)	2	0/26 (0.00%)	0
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MGH IRB 4.12.07

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The sponsor shall require the PI to furnish the sponsor with a copy of any proposed publication at least 60 days prior to submission. The sponsor shall be entitled to review such proposed publications. The PI shall give due regard to the sponsor's comments on the proposed publication. If the sponsor reasonably believes a patent application claiming an invention should be filed prior to such publication, such submission shall not be submitted until applicable patent applications have been filed.

Results Point of Contact

• Name/Title: Dr. Naomi Simon
• Organization: Massachusetts General Hospital
• Phone: 617-726-7913
• EMail: nsimon@partners.org

• Responsible Party: Naomi M. Simon, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01398514 History of Changes
• Other Study ID Numbers: 2008-P-001314
• First Submitted: July 12, 2011
• First Posted: July 20, 2011
• Results First Submitted: July 25, 2013
• Results First Posted: September 27, 2013
• Last Update Posted: June 11, 2014