- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01214044
Circadian Effects of Escitalopram
Determination of the Circadian Resetting Effects of Escitalopram and Testing for Correlations Between Circadian Resetting and Antidepressant Effects
Study Overview
Detailed Description
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
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Oregon
-
Portland, Oregon, United States, 97239
- Oregon Health & Science University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 18-65 years old
- able to comply with requirements of the experimental protocol
- competent to sign informed consent
- have mild to severe major depressive disorder without psychotic features and without a seasonal pattern
- currently be under the care of a licensed mental health care provider or primary care physician
- Score > 7 when interviewed by a trained rater using the 21-Item Hamilton Depression Scale (HAM-D)
- be in good physical health
- not be suicidal
- not be taking any other antidepressant medications besides escitalopram during the study
- be free of antidepressant medications for 2-4 weeks prior to beginning the study
- not have a history of transmeridian travel or shift work in the past 2 months and have no plans for transmeridian travel or shift work for the duration of the study
- be able to maintain a regular sleep wake schedule for the weeks one and nine of study
- women of childbearing potential must have a negative pregnancy test and practice an acceptable method of birth control
Exclusion Criteria:
- abnormal heart, liver, or kidney function
- significant laboratory abnormalities on Complete Blood Count, Complete Metabolic Set, Thyroid Stimulating Hormone, EKG, & urinalysis
- shift work or transmeridian travel in the last 2 months
- current use of melatonin
- evidence of a primary sleep disorder by history
- women who are pregnant or lactating
- be taking medications with known sedative or stimulating effects or that would interfere with the production of melatonin
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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). |
8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram)
|
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.
|
8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram)
|
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 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.
|
8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram)
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Jonathan Emens, MD, Oregon Health and Science University
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Depression
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Parasympatholytics
- Autonomic Agents
- Peripheral Nervous System Agents
- Muscarinic Antagonists
- Cholinergic Antagonists
- Cholinergic Agents
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Antidepressive Agents, Second-Generation
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Citalopram
- Dexetimide
Other Study ID Numbers
- LXP-MD-132
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Depression
-
ProgenaBiomeRecruitingDepression | Depression, Postpartum | Depression, Anxiety | Depression Moderate | Depression Severe | Clinical Depression | Depression in Remission | Depression, Endogenous | Depression ChronicUnited States
-
Washington University School of MedicineCompletedTreatment Resistant Depression | Late Life Depression | Geriatric Depression | Refractory Depression | Therapy-Resistant DepressionUnited States, Canada
-
Kintsugi Mindful Wellness, Inc.Sonar Strategies; Vituity PsychiatryRecruitingDepression | Depression Moderate | Depression Severe | Depression MildUnited States
-
University of California, San FranciscoRecruitingDepression Moderate | Depression Mild | Depression, TeenUnited States
-
University GhentUniversiteit Antwerpen; Janssen-Cilag Ltd.RecruitingDepression Moderate | Depression Severe | Depression MildBelgium
-
Baylor College of MedicineUniversity of TexasRecruitingDepression | Depression Moderate | Depression Severe | Suicide and Self-harm | Depression in Adolescence | Depression MildUnited States
-
University of Cape TownNational Institute of Mental Health (NIMH)CompletedPostpartum Depression | Clinical Depression | Moderate DepressionSouth Africa
-
Washington University School of MedicinePatient-Centered Outcomes Research Institute; National Institute of Mental...CompletedMajor Depressive Disorder | Treatment Resistant Depression | Treatment-Refractory Depression | Late Life Depression | Geriatric DepressionUnited States, Canada
-
Northern Illinois UniversityUniversity Autonoma de Santo DomingoTerminatedDepression Moderate | Depression MildUnited States, Dominican Republic
-
Lawson Health Research InstituteTerminated
Clinical Trials on placebo/escitalopram
-
Rigshospitalet, DenmarkUniversity of Cambridge; Lundbeck FoundationCompleted
-
Boston UniversityCompletedCoronary Artery Disease
-
Shanghai Municipal Hospital of Traditional Chinese...Shanghai Mental Health Center; Xuhui Central Hospital, Shanghai; Shanghai Huangpu...Recruiting
-
Johns Hopkins UniversityMedical University of South Carolina; University of South Carolina; University... and other collaboratorsRecruiting
-
Universidade do PortoCompletedSpinal Cord InjuriesPortugal
-
Shanghai 7th People's HospitalNot yet recruitingDepressive Disorder, MajorChina
-
Ryerson UniversityUnknownInsomnia | Major Depressive DisorderCanada
-
University of PennsylvaniaWashington University School of MedicineCompleted
-
First Affiliated Hospital of Zhejiang UniversityRecruitingAdolescent | Depressive DisorderChina
-
University of California, Los AngelesUnknownInsomnia | Major Depressive DisorderUnited States