Circadian Effects of Escitalopram

• ClinicalTrials.gov Identifier: NCT01214044
• Recruitment Status: Completed
• First Posted: October 4, 2010
• Results First Posted: August 6, 2019
• Last Update Posted: August 20, 2019
• Sponsor: Oregon Health and Science University
• Collaborator: Forest Laboratories
• Information provided by (Responsible Party): Jonathan Emens, Oregon Health and Science University

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Depression
• Intervention: Drug: placebo/escitalopram
• Enrollment: 19

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Study Drug
Arm/Group Description	Subjects will have a total of 12 visits to Oregon Clinical & Translational Research Institute at Oregon Health & Science University over the 14-16 weeks of study. Subjects will first undergo an initial screening visit to determine eligibility. Subjects who meet criteria will then stop taking their current antidepressant medication (if applicable), during which time the study doctor and staff will conduct weekly mood assessments to ensure safety. Subjects will then have a study initiation/materials visit followed by 9 visits during treatment with placebo or escitalopram. A final post-study follow-up safety visit will be scheduled at the end of treatment. placebo/escitalopram: Subjects will first complete a one week, single-blind placebo lead in phase. Subjects will then receive escitalopram for 8 weeks. Subjects will receive 10 mg/day for the first 2 weeks of active treatment, and then 20 mg/day for the remaining 6 weeks of treatment. Medication will be dispensed on a weekly basis.
Period Title: Visit 1: Screening and Consent, Washout
Started	31
Completed	19
Not Completed	12
Reason Not Completed
Withdrawal by Subject	5
Ineligible	3
Lost to Follow-up	4
Period Title: Visit 2: End Washout & Start Placebo
Started	19
Completed	17 [1]
Not Completed	2
[1] 2 subjects dropped out during the placebo week (between study visits 2 & 3)
Period Title: Visits 3-5: Escitalopram 10 mg Daily
Started	17
Completed	14
Not Completed	3
Reason Not Completed
Withdrawal by Subject	3
Period Title: Visits 6-11: Escitalopram 20 mg Daily
Started	14
Completed	10
Not Completed	4
Reason Not Completed
Withdrawal by Subject	3
Adverse Event	1

Baseline Characteristics

Arm/Group Title		Study Drug
Arm/Group Description		Subjects will have a total of 12 visits to Oregon Clinical & Translational Research Institute at Oregon Health & Science University over the 14-16 weeks of study. An initial screening visit will determine eligibility. Subjects who meet criteria and agree to participate will then stop taking their current antidepressant medication (if applicable), during which time the study doctor and staff will conduct weekly mood assessments to ensure safety. Subjects will then have a study initiation/materials visit followed by 9 visits during treatment with placebo or escitalopram. A final post-study follow-up safety visit will be scheduled at the end of treatment. Placebo/escitalopram: Subjects will first complete a one week, single-blind placebo lead in phase. Subjects will then receive escitalopram for 8 weeks. Subjects will receive 10 mg/day for the first 2 weeks of active treatment, and then 20 mg/day for the remaining 6 weeks of treatment. Medication will be dispensed weekly.
Overall Number of Baseline Participants		10
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	10 100.0%
	>=65 years	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	10 participants
		50.2 (13.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants
	Female	5 50.0%
	Male	5 50.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	10 participants
		10

Outcome Measures

1. Primary Outcome

Title	Change in Dim Light Melatonin Onset
Description	The Dim Light Melatonin Onset (DLMO) is the time of the onset of melatonin secretion under dim light conditions using the equivalent thresholds of 10 pg/ml in plasma and 3 pg/ml in saliva. It is a marker of biological time. Data are provided in decimal and military time (e.g., 9:30 pm equals 21.50). This measure is used to determine if there was a change in the time of the dim light melatonin onset (DLMO) before treatment with escitalopram (at Study Visit 3) and after treatment with escitalopram (at Study Visit 11).
Time Frame	8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram)

Outcome Measure Data

Analysis Population Description

Of the 10 subjects who completed all study procedures, adequate dim light melatonin data from both study visits 3 and 11 were available for 9 subjects.

Arm/Group Title	Study Drug
Arm/Group Description:	Subjects will have a total of 12 visits to Oregon Clinical & Translational Research Institute at Oregon Health & Science University over the 14-16 weeks of study. An initial screening visit will determine eligibility. Subjects who meet criteria and agree to participate will then stop taking their current antidepressant medication (if applicable), during which time the study doctor and staff will conduct weekly mood assessments to ensure safety. Subjects will then have a study initiation/materials visit followed by 9 visits during treatment with placebo or escitalopram. A final post-study follow-up safety visit will be scheduled at the end of treatment. Placebo/escitalopram: Subjects will first complete a one week, single-blind placebo lead in phase. Subjects will then receive escitalopram for 8 weeks. Subjects will receive 10 mg/day for the first 2 weeks of active treatment, and then 20 mg/day for the remaining 6 weeks of treatment. Medication will be dispensed weekly.
Overall Number of Participants Analyzed	9
Mean (Standard Deviation); Unit of Measure: decimal military time (hours)
Baseline DLMO	21.17 (1.24)
Post-escitalopram DLMO	20.77 (1.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug
	Comments	A within subjects comparison was done to compare the time of the dim light melatonin onset before treatment with escitalopram (Study Visit 3) and after treatment with escitalopram (Study Visit 11).
	Type of Statistical Test	Other
	Comments	A paired t-test was done to see if the time of the dim light melatonin onset changed from baseline to post-treatment.
Statistical Test of Hypothesis	P-Value	0.2
	Comments	A priori threshold for significance was p = 0.05.
	Method	t-test, 2 sided
	Comments	paired t-test

2. Secondary Outcome

Title	Change in Hamilton Depression Rating Scale (HAM-D) Scores
Description	The HAM-D is the total score on the 21-question Hamilton Depression Rating Scale. Scores range from 0 to 53 with higher scores indicating worse symptoms of depression.
Time Frame	8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram)

Outcome Measure Data

Analysis Population Description

Of the 10 subjects who completed all study procedures, adequate Hamilton Depression Rating Scale data from both study visits 3 and 11 were available for 7 subjects.

Arm/Group Title	Study Drug
Arm/Group Description:	Subjects will have a total of 12 visits to Oregon Clinical & Translational Research Institute at Oregon Health & Science University over the 14-16 weeks of study. An initial screening visit will determine eligibility. Subjects who meet criteria and agree to participate will then stop taking their current antidepressant medication (if applicable), during which time the study doctor and staff will conduct weekly mood assessments to ensure safety. Subjects will then have a study initiation/materials visit followed by 9 visits during treatment with placebo or escitalopram. A final post-study follow-up safety visit will be scheduled at the end of treatment. placebo/escitalopram: Subjects will first complete a one week, single-blind placebo lead in phase. Subjects will then receive escitalopram for 8 weeks. Subjects will receive 10 mg/day for the first 2 weeks of active treatment, and then 20 mg/day for the remaining 6 weeks of treatment. Medication will be dispensed on a weekly basis.
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: units on scale (scores)
	-2.3 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug
	Comments	We hypothesized that there would be a decrease in the Hamilton-21 score with escitalopram treatment. A within subjects comparison was done to compare the Hamilton-21 score before treatment with escitalopram (Study Visit 3) and after treatment with escitalopram (Study Visit 11).
	Type of Statistical Test	Other
	Comments	A paired t-test was done to see if the Hamilton-21 score decreased from baseline to post-treatment.
Statistical Test of Hypothesis	P-Value	0.01
	Comments	A priori threshold for significance was p = 0.05.
	Method	t-test, 1 sided
	Comments	paired t-test

3. Secondary Outcome

Title	Change in Beck Depression Inventory II (BDI-II) Scores
Description	The BDI-II is the total score on the 21-question Beck Depression Inventory II questionnaire. Scores range from 0 to 63 with higher scores indicating worse symptoms of depression.
Time Frame	8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram)

Outcome Measure Data

Analysis Population Description

Of the 10 subjects who completed all study procedures, Beck Depression Inventory-II data from both study visits 3 and 11 were available for 7 subjects.

Arm/Group Title	Study Drug
Arm/Group Description:	Subjects will have a total of 12 visits to Oregon Clinical & Translational Research Institute at Oregon Health & Science University over the 14-16 weeks of study. An initial screening visit will determine eligibility. Subjects who meet criteria and agree to participate will then stop taking their current antidepressant medication (if applicable), during which time the study doctor and staff will conduct weekly mood assessments to ensure safety. Subjects will then have a study initiation/materials visit followed by 9 visits during treatment with placebo or escitalopram. A final post-study follow-up safety visit will be scheduled at the end of treatment. placebo/escitalopram: Subjects will first complete a one week, single-blind placebo lead in phase. Subjects will then receive escitalopram for 8 weeks. Subjects will receive 10 mg/day for the first 2 weeks of active treatment, and then 20 mg/day for the remaining 6 weeks of treatment. Medication will be dispensed on a weekly basis.
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: units on scale (scores)
	-3.3 (7.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug
	Comments	We hypothesized that there would be a decrease in the Beck Depression Inventory-II score with escitalopram treatment. A within subjects comparison was done to compare the Beck Depression Inventory-II score before treatment with escitalopram (Study Visit 3) and after treatment with escitalopram (Study Visit 11).
	Type of Statistical Test	Other
	Comments	A paired t-test was done to see if the Beck Depression Inventory-II score decreased from baseline to post-treatment.
Statistical Test of Hypothesis	P-Value	0.14
	Comments	A priori threshold for significance was p = 0.05.
	Method	t-test, 1 sided
	Comments	paired t-test

4. Secondary Outcome

Title	Change in Phase Angle Difference (PAD)
Description	The PAD is the time interval (number of hours) between the Dim Light Melatonin Onset (DLMO) and the average midpoint of sleep during the prior week. Larger PADs indicate a longer time interval between the DLMO and midpoint of sleep. A negative change in PAD value indicates a shortening of the time interval from Study Visit 3 to Study Visit 11.
Time Frame	8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram)

Outcome Measure Data

Analysis Population Description

Of the 10 subjects who completed all study procedures, adequate PAD data from both study visits 3 and 11 (derived from dim light melatonin onset and sleep diary) were available for 7 subjects.

Arm/Group Title	Study Drug
Arm/Group Description:	Subjects will have a total of 12 visits to Oregon Clinical & Translational Research Institute at Oregon Health & Science University over the 14-16 weeks of study. An initial screening visit will determine eligibility. Subjects who meet criteria and agree to participate will then stop taking their current antidepressant medication (if applicable), during which time the study doctor and staff will conduct weekly mood assessments to ensure safety. Subjects will then have a study initiation/materials visit followed by 9 visits during treatment with placebo or escitalopram. A final post-study follow-up safety visit will be scheduled at the end of treatment. placebo/escitalopram: Subjects will first complete a one week, single-blind placebo lead in phase. Subjects will then receive escitalopram for 8 weeks. Subjects will receive 10 mg/day for the first 2 weeks of active treatment, and then 20 mg/day for the remaining 6 weeks of treatment. Medication will be dispensed on a weekly basis.
Overall Number of Participants Analyzed	7
Mean (Standard Deviation); Unit of Measure: hours
	-0.6 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Drug
	Comments	We hypothesized that there would be a correlation between the change in phase angle difference and the decrease in the Hamilton-21 score with escitalopram treatment. The phase angle difference is the interval, in hours, between the dim light melatonin onset (a marker of biological time) and the average midpoint of sleep during the prior week.
	Type of Statistical Test	Other
	Comments	Spearman's rank-order correlation (non-parametric test) was used.
Statistical Test of Hypothesis	P-Value	0.06
	Comments	Spearman's rho (rs) = 0.66
	Method	Spearman's rank-order correlation
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Study Drug
	Comments	We hypothesized that there would be a correlation between the change in phase angle difference and the decrease in the Beck Depression Inventory-II score with escitalopram treatment. The phase angle difference is the interval, in hours, between the dim light melatonin onset (a marker of biological time) and the average midpoint of sleep during the prior week.
	Type of Statistical Test	Other
	Comments	Spearman's rank-order correlation (non-parametric test) was used.
Statistical Test of Hypothesis	P-Value	0.48
	Comments	Spearman's rho (rs) = 0.02
	Method	Spearman's rank-order correlation
	Comments	[Not Specified]

Adverse Events

Time Frame	Participants were assessed over 14 weeks (or 16 weeks in two subjects who were on fluoxetine at enrollment and therefore had a 4-week, instead of a 2-week, washout period per the protocol). Subjects had a weekly contact with study personnel throughout the 14 or 16 weeks of study except for the two week medication taper period between the last two study visits.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Visit 1: Screening & Consent, Washout		Visit 2: End Washout & Start Placebo		Visits 3-5: Escitalopram 10 mg Daily		Visits 6-11: Escitalopram 20 mg Daily
Arm/Group Description	Subjects will have a total of 12 visits to Oregon Clinical & Translational Research Institute at Oregon Health & Science University over the 14-16 weeks of study. An initial screening visit will determine eligibility. Subjects who meet criteria and agree to participate will then stop taking their current antidepressant medication (if applicable), during which time the study doctor and staff will conduct weekly mood assessments to ensure safety.		After completing the washout period, Subjects will then complete a one week, single-blind placebo lead in phase.		After the week of placebo, Subjects will then receive 10 mg/day of escitalpram for the first 2 weeks of active treatment.		After receiving 10 mg/day of escitalopram for 2 weeks, subjects will then receive escitalopram, 20 mg/day for the remaining 6 weeks of treatment.
All-Cause Mortality
	Visit 1: Screening & Consent, Washout		Visit 2: End Washout & Start Placebo		Visits 3-5: Escitalopram 10 mg Daily		Visits 6-11: Escitalopram 20 mg Daily
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/31 (0.00%)		0/19 (0.00%)		0/17 (0.00%)		0/14 (0.00%)
Serious Adverse Events
	Visit 1: Screening & Consent, Washout		Visit 2: End Washout & Start Placebo		Visits 3-5: Escitalopram 10 mg Daily		Visits 6-11: Escitalopram 20 mg Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0.00%)		0/19 (0.00%)		0/17 (0.00%)		1/14 (7.14%)
Psychiatric disorders
suicide attempt * [1]	0/31 (0.00%)	0	0/19 (0.00%)	0	0/17 (0.00%)	0	1/14 (7.14%)	1
* Indicates events were collected by non-systematic assessment; [1] In this cohort of subjects with mild to severe Major Depressive Disorder, one subject was admitted to an outside hospital following a suicide attempt and was subsequently transferred to outpatient facility for ongoing treatment.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Visit 1: Screening & Consent, Washout		Visit 2: End Washout & Start Placebo		Visits 3-5: Escitalopram 10 mg Daily		Visits 6-11: Escitalopram 20 mg Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0.00%)		0/19 (0.00%)		1/17 (5.88%)		0/14 (0.00%)
Nervous system disorders
Headache * [1]	0/31 (0.00%)	0	0/19 (0.00%)	0	1/17 (5.88%)	1	0/14 (0.00%)	0
* Indicates events were collected by non-systematic assessment; [1] One subject reported the onset of a headache around 6 pm with subsequent feelings of her heart racing, feeling flushed in her face & neck and some itchiness. The symptoms resolved after 2 hours.

Limitations and Caveats

The sample size was small because this was a preliminary study that aimed to collect pilot data.

More Information

Certain Agreements

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

There is NOT 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.

Results Point of Contact

• Name/Title: Jonathan Emens, M.D.
• Organization: Oregon Health & Science University and VA Portland Health Care System
• Phone: 503-220-8262 ext 58490
• EMail: emensj@ohsu.edu

• Responsible Party: Jonathan Emens, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT01214044
• Other Study ID Numbers: LXP-MD-132
• First Submitted: October 1, 2010
• First Posted: October 4, 2010
• Results First Submitted: November 28, 2018
• Results First Posted: August 6, 2019
• Last Update Posted: August 20, 2019