Circadian Effects of Escitalopram
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|ClinicalTrials.gov Identifier: NCT01214044|
Recruitment Status : Completed
First Posted : October 4, 2010
Results First Posted : August 6, 2019
Last Update Posted : August 6, 2019
|Condition or disease||Intervention/treatment||Phase|
|Depression||Drug: placebo/escitalopram||Not Applicable|
Background: The human biological clock (circadian pacemaker) has long been thought to play a role in non-seasonal depression. A connection is suggested by the demonstration of 24-hour rhythms in mood, subjective and objective changes in sleep with depression, and reports of changes in the timing and amplitude of biological rhythms in depression. Furthermore, it is known that the neurotransmitter serotonin has a significant role in regulating biological rhythms and that drugs that act on serotonin (such as some antidepressants) are able to reset the biological clock in animals.
Objective: The aim of the study is to obtain preliminary data that will test whether the antidepressant medication escitalopram has a resetting effect on the human biological clock and whether the improvement in depression symptoms with escitalopram correlates with the degree to which the timing of the biological clock is realigned with the timing of sleep.
Design: 14-16-week, fixed dose (after titration), open label trial.
Setting and Subjects: 50 individuals will be screened for participation. 15 individuals with unipolar, non-seasonal depression will be studied over 1 year.
Intervention: Subjects will first complete a one week, single-blind placebo lead-in phase. Subjects will then receive escitalopram for 8 weeks (10 mg/day for the first 2 weeks of treatment and then 20mg/day for the remaining 6 weeks of treatment).
Measurements: Subjects will keep a sleep diary and wear a wrist activity monitor throughout the study to document the timing and quality of sleep. On two occasions (end of placebo week and end of last treatment week) blood and/or saliva will be sampled every 30 minutes for 7 hours and the resulting samples will be assayed for melatonin. The onset of melatonin secretion (dim light melatonin onset or DLMO) will be used to mark the timing of the biological clock (circadian phase). Circadian misalignment will be measured using the time interval between the DLMO and the average midsleep of the prior week (phase angle difference or PAD). Mood will be assessed throughout the study using the Hamilton Depression Rating Scale (HAM-D) as well as the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Determination of the Circadian Resetting Effects of Escitalopram and Testing for Correlations Between Circadian Resetting and Antidepressant Effects|
|Actual Study Start Date :||May 2008|
|Actual Primary Completion Date :||December 2011|
|Actual Study Completion Date :||December 2011|
Experimental: Study Drug
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 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.
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.
- Change in Dim Light Melatonin Onset [ Time Frame: 8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram) ]
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).
- Change in Hamilton Depression Rating Scale (HAM-D) Scores [ Time Frame: 8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram) ]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.
- Change in Beck Depression Inventory II (BDI-II) Scores [ Time Frame: 8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram) ]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.
- Change in Phase Angle Difference (PAD) [ Time Frame: 8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram) ]
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 numbers indicate a longer time interval between the DLMO and midpoint of sleep.
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.
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.
These three measures are used to determine if there is a correlation (Spearman's rank-order correlation, Spearman's Rho or rs) between the change in the Hamilton-21 and Beck Depression Inventory-II scores with escitalopram treatment and the change in the phase angle difference.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01214044
|United States, Oregon|
|Oregon Health & Science University|
|Portland, Oregon, United States, 97239|
|Principal Investigator:||Jonathan Emens, MD||Oregon Health and Science University|