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Over 18% of Americans aged 65 years and older have depression. Recent evidence suggests that there is a link between depression and inflammatory disease. This study investigates the relationship between inflammation in the brain and depression. Comparing biological and psychological differences in depressed and non-depressed people allows researchers to find better ways to treat and prevent depression. All participants will have: neuropsychological tests, an EKG, a spinal tap, a blood draw, and, if depressed, given either an antidepressant coupled with an anti-inflammatory medication or an anti-depressant coupled with a placebo for six weeks. The investigators are trying to correlate brain function with depression levels and biomarkers from the blood and spinal fluid.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | No Intervention | This arm is for participants who are not depressed. | |
| Experimental - treatment | Experimental | Depressed participants will receive an antidepressant (escitalopram) AND either a non-steroidal anti-inflammatory drug (celecoxib) OR placebo (sugar pill) for 6 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Escitalopram + Celecoxib | Drug | Participants will receive celecoxib in addition to escitalopram |
|
| Measure | Description | Time Frame |
|---|---|---|
| IL-6 Levels | IL6 levels were measured in participants by blood draw 6 weeks after the first dose was given. | up to week 6 |
| Montgomery Asberg Depression Rating Scale (MADRS) | This depression rating scale will be used to determine clinical outcome for depressed participants. Scores range from 0-60. The higher the score, the worse the outcome (see below) Normal: 0-6 Mild Depression: 7-19 Moderate Depression: 20-34 Severe Depression: 35+ Very Severe Depression: 60 | Week 6 |
| IL10 Levels | IL10 levels were measured in participants by blood draw 6 weeks after the first dose was given | up to 6 weeks |
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Inclusion Criteria:
Additional Inclusion Criteria for Depressed Participants:
Exclusion Criteria:
Additional Exclusion Criteria for Depressed Subjects:
1) Active suicidality or current suicidal risk as determined by the investigator
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| Name | Affiliation | Role |
|---|---|---|
| Yvette Sheline | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35332134 | Derived | Luning Prak ET, Brooks T, Makhoul W, Beer JC, Zhao L, Girelli T, Skarke C, Sheline YI. No increase in inflammation in late-life major depression screened to exclude physical illness. Transl Psychiatry. 2022 Mar 24;12(1):118. doi: 10.1038/s41398-022-01883-4. |
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Total recruitment was 119 but 24 screen failed so the actual recruitment was 95
SEPTA and PATCO advertisements, radio advertisements on WHYY, WMGK, and WURD, Newspaper advertisements in Metro, Milestones, Golden Times, and Haddonfield Sun, recruitment flyers, iConnect, emailing doctors for referrals, and advertising in clinics
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| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Control | Participants do not meet DSM-IV criteria for MDD, and did not receive any medication throughout the study |
| FG001 | Experimental - Placebo | Participants meet DSM-IV criteria for MDD, and received placebo pills for the 6 week duration of the study |
| FG002 | Escitalopram | Participants meet DSM-IV criteria for MDD and received a dose of escitalopram between 10-20mg, or a 10-20mg dose of escitalopram as well as a placebo pill daily for the 6 week duration of the study. |
| FG003 | Escitalopram + Celecoxib | Participants meet DSM-IV criteria for MDD and received a 10-20mg dose of escitalopram and a 400mg dose of celecoxib daily for the 6 week duration of the study |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Control | Participants do not meet DSM-IV criteria for MDD, and did not receive any medication throughout the study |
| BG001 | Placebo | Participants meet DSM-IV criteria for MDD, and received placebo pills for the 6 week duration of the study |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | IL-6 Levels | IL6 levels were measured in participants by blood draw 6 weeks after the first dose was given. | Not everybody completed the final blood draw | Posted | Mean | Standard Deviation | pg/mL | up to week 6 |
|
Baseline to 6 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Healthy Control | Participants do not meet DSM-IV criteria for MDD, and did not receive any medication throughout the study |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated Blood Pressure | Cardiac disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vasovagal Response | Vascular disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Yvette Sheline, McLure Professor of Radiology, Neurology and Psychiatry | University of Pennsylvania | (215) 573-0082 | sheline@pennmedicine.upenn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 19, 2019 | Aug 14, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 4, 2020 | Jul 18, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000089983 | Escitalopram |
| D000068579 | Celecoxib |
| ID | Term |
|---|---|
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009570 | Nitriles |
| D001572 |
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| Escitalopram + Placebo | Drug | Participants will receive a placebo in addition to escitalopram. |
|
| Physician Decision |
|
| Withdrawal by Subject |
|
| BG002 | Escitalopram | Participants meet DSM-IV criteria for MDD and received a dose of escitalopram between 10-20mg, or a 10-20mg dose of escitalopram as well as a placebo pill daily for the 6 week duration of the study. |
| BG003 | Escitalopram + Celecoxib | Participants meet DSM-IV criteria for MDD and received a 10-20mg dose of escitalopram and a 400mg dose of celecoxib daily for the 6 week duration of the study |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Montgomery Asberg Depression Rating Scale (MADRS) | This depression rating scale will be used to determine clinical outcome for depressed participants. Scores range from 0-60. The higher the score, the worse the outcome (see below) Normal: 0-6 Mild Depression: 7-19 Moderate Depression: 20-34 Severe Depression: 35+ Very Severe Depression: 60 | Mean | Standard Deviation | Total score (sum of points) |
|
| IL-6 Levels | Mean | Standard Deviation | pg/mL |
|
| IL-10 Levels | Mean | Standard Deviation | pg/mL |
|
Participants meet DSM-IV criteria for MDD and received a dose of escitalopram between 10-20mg, or a 10-20mg dose of escitalopram as well as a placebo pill daily for the 6 week duration of the study. |
| OG003 | Escitalopram + Celecoxib | Participants meet DSM-IV criteria for MDD and received a 10-20mg dose of escitalopram and a 400mg dose of celecoxib daily for the 6 week duration of the study |
|
|
|
| Primary | Montgomery Asberg Depression Rating Scale (MADRS) | This depression rating scale will be used to determine clinical outcome for depressed participants. Scores range from 0-60. The higher the score, the worse the outcome (see below) Normal: 0-6 Mild Depression: 7-19 Moderate Depression: 20-34 Severe Depression: 35+ Very Severe Depression: 60 | Posted | Mean | Standard Deviation | Total Score (Sum of Points) | Week 6 |
|
|
|
|
| Primary | IL10 Levels | IL10 levels were measured in participants by blood draw 6 weeks after the first dose was given | Not everybody completed the last blood draw | Posted | Mean | Standard Deviation | pg/mL | up to 6 weeks |
|
|
|
|
| 0 |
| 30 |
| 0 |
| 30 |
| 0 |
| 30 |
| EG001 | Placebo | Participants meet DSM-IV criteria for MDD, and receieved placebo pills daily for the 6 week duration of the study Escitalopram + Placebo: Participants will receive a placebo in addition to escitalopram. | 0 | 20 | 0 | 20 | 1 | 20 |
| EG002 | Escitalopram | Participants meet DSM-IV criteria for MDD and received a dose of escitalopram between 10-20mg, or a 10-20mg dose of escitalopram as well as a placebo pill daily for the 6 week duration of the study. | 0 | 29 | 2 | 29 | 7 | 29 |
| EG003 | Escitalopram + Celecoxib | Participants meet DSM-IV criteria for MDD and received a 10-20mg dose of escitalopram and a 400mg dose of celecoxib daily for the 6 week duration of the study | 0 | 16 | 2 | 16 | 9 | 16 |
| Dizziness | General disorders | Non-systematic Assessment |
|
| Confusion | Nervous system disorders | Non-systematic Assessment |
|
| Bradycardia | Cardiac disorders | Non-systematic Assessment |
|
| Thoughts of Suicide in Response to Cognitive Task Item | Psychiatric disorders | Non-systematic Assessment |
|
| Suicidal Ideation | Psychiatric disorders | Non-systematic Assessment |
|
| Headache | General disorders | Non-systematic Assessment |
|
| Dizziness/Light Headed | Nervous system disorders | Non-systematic Assessment |
|
| Jittery | Nervous system disorders | Non-systematic Assessment |
|
| Urinating Frequently | Renal and urinary disorders | Non-systematic Assessment |
|
| Yawning Frequently | General disorders | Non-systematic Assessment |
|
| Claustophobia | Psychiatric disorders | Non-systematic Assessment |
|
| Loss of Libido | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Skin Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Grinding Teeth | Ear and labyrinth disorders | Non-systematic Assessment |
|
| More Tired/Lethargy | Nervous system disorders | Non-systematic Assessment |
|
| Dry Mouth | General disorders | Non-systematic Assessment |
|
| Withdraw Symptoms from Discontinuing Escitalopram Improperly | Psychiatric disorders | Non-systematic Assessment |
|
| Elevated Blood Pressure | Cardiac disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Slipped on Escalator When Leaving Visit | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Sore Chest | Surgical and medical procedures | Non-systematic Assessment |
|
| Sore Lower Back | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Change in Sleep Pattern | General disorders | Non-systematic Assessment |
|
| Sexual Side Effect Delayed Ejaculation | Reproductive system and breast disorders | Non-systematic Assessment |
|
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| Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
|
|
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Wilcoxon (Mann-Whitney) |
| <.001 |
| Superiority |
| MADRS scores at the final visit compared between the healthy control and placebo groups | Wilcoxon (Mann-Whitney) | .034 | Superiority |
| MADRS scores at the final visit compared between the placebo groups and all groups receiving escitalopram (both with and without celecoxib) | ANCOVA | .03 | Superiority |
| .19 |
| Other |
| IL10 levels in the escitalopram group pre- and post-treatment compared using a paired t-test | t-test, 2 sided | .5 | Other |
| IL10 levels in the escitalopram + celecoxib group pre- and post-treatment compared using a paired t-test | t-test, 2 sided | .55 | Other |
| IL10 levels at completion of study compared between all MDD groups (placebo, escitalopram, and escitalopram + celecoxib) and the healthy control group | t-test, 2 sided | .06 | Other |