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Stress and Inflammation in Late-Life Depression (S&I)

Primary Purpose

Depression, Inflammation

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Escitalopram + Celecoxib
Escitalopram + Placebo
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depression focused on measuring Depression, Geriatric, Inflammation

Eligibility Criteria

50 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Age 18-80, male or female, any race;
  2. Absence of clinical dementia
  3. English speaking
  4. Blood pressure not exceeding 150/90 mmHg, treated or untreated
  5. Weight greater than 110 lbs
  6. Normal result on liver-function test
  7. No history of ulcer disease or GI bleeding
  8. No renal insufficiency

Additional Inclusion Criteria for Depressed Participants:

  1. DSM-IV criteria for Major Depressive Disorder
  2. HAM-D greater than 18

Exclusion Criteria:

  1. Known history of relevant severe drug allergy or hypersensitivity (e.g. to Citalopram or Escitalopram, and/or to celecoxib, aspirin, or other NSAIDs only for Phase 2; known demonstration of allergic-type reactions to sulfonamides);
  2. Does not speak English;
  3. Cannot give informed consent;
  4. MRI contraindications (e.g., foreign metallic implants, pacemaker);
  5. Known primary neurological disorders, such as Parkinson's disease, Alzheimer's disease, traumatic brain injury, cognitive impairment or dementia,
  6. Known severe inflammatory disease such as systemic lupus erythematosis, known autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis; Screen + for RF, ANA, HIV, Hepatitis B or C.
  7. Clinical Dementia Rating Scale score greater than 0;
  8. Diagnosis of a chronic psychiatric illness other than MDD at the discretion of the study doctor;
  9. Significant handicaps (e.g. uncorrected hearing or visual impairment, mental retardation) that would interfere with testing;
  10. Bleeding diathesis;
  11. Severe Medical problem, which in the opinion of the investigator would pose a safety risk to the subject;
  12. Clinically significant cardiovascular disease that will be assessed on a case-by-case basis. Clinically significant cardiovascular disease usually includes one or more of the following: cardiac surgery or myocardial infarction within the last 4 weeks; unstable angina; acute decompensated congestive heart failure or class IV heart failure; current significant cardiac arrhythmia or conduction disturbance, particularly those resulting in ventricular fibrillation, or causing syncope or near syncope; uncontrolled high blood pressure; QTc greater than 450msec (by history for subjects with cardiac disease); documented prior stroke;
  13. Clinically significant abnormalities on EKG. Primary AV block or Right bundle branch block are not necessarily exclusionary;
  14. Current diagnosis of cancer
  15. Current diagnosis of HIV, active Hepatitis B and/or Hepatitis C
  16. Use of an Investigational medicine within the past 30 days;
  17. Use of Coumadin, Warfarin within the past 2 months;
  18. Current treatment with psychotropic drugs or drugs that affect the CNS such as beta-blockers, mood stabilizers, antipsychotics, steroids or non-steroidal anti-inflammatory medications or other antidepressants. No subjects will be included in the study unless they have been off all psychotropics for at least 3 weeks, except in the case of fluoxetine, where 5 weeks off treatment will be required;
  19. Current alcohol or substance abuse disorder, schizophrenia or other psychotic disorder, bipolar disorder, or current OCD;
  20. Abnormal liver-function test
  21. History of ulcer disease, Chron's disease, GI bleeding or anemia
  22. Weight less than 110 lbs
  23. Renal insufficiency
  24. Any other factor that in the investigator's judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from this facility);

Additional Exclusion Criteria for Depressed Subjects:

1) Active suicidality or current suicidal risk as determined by the investigator

Sites / Locations

  • University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Control

Experimental - treatment

Arm Description

This arm is for participants who are not depressed.

Depressed participants will receive an antidepressant (escitalopram) AND either a non-steroidal anti-inflammatory drug (celecoxib) OR placebo (sugar pill) for 6 weeks.

Outcomes

Primary Outcome Measures

IL-6 Levels
IL6 levels were measured in participants by blood draw 6 weeks after the first dose was given.
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
IL10 Levels
IL10 levels were measured in participants by blood draw 6 weeks after the first dose was given

Secondary Outcome Measures

Full Information

First Posted
February 27, 2015
Last Updated
September 18, 2023
Sponsor
University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT02389465
Brief Title
Stress and Inflammation in Late-Life Depression
Acronym
S&I
Official Title
Stress and Inflammation in the Pathophysiology of Late Life Depression
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
July 18, 2022 (Actual)
Study Completion Date
July 18, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Inflammation
Keywords
Depression, Geriatric, Inflammation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
119 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
No Intervention
Arm Description
This arm is for participants who are not depressed.
Arm Title
Experimental - treatment
Arm Type
Experimental
Arm Description
Depressed participants will receive an antidepressant (escitalopram) AND either a non-steroidal anti-inflammatory drug (celecoxib) OR placebo (sugar pill) for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Escitalopram + Celecoxib
Intervention Description
Participants will receive celecoxib in addition to escitalopram
Intervention Type
Drug
Intervention Name(s)
Escitalopram + Placebo
Intervention Description
Participants will receive a placebo in addition to escitalopram.
Primary Outcome Measure Information:
Title
IL-6 Levels
Description
IL6 levels were measured in participants by blood draw 6 weeks after the first dose was given.
Time Frame
up to week 6
Title
Montgomery Asberg Depression Rating Scale (MADRS)
Description
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
Time Frame
Week 6
Title
IL10 Levels
Description
IL10 levels were measured in participants by blood draw 6 weeks after the first dose was given
Time Frame
up to 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age 18-80, male or female, any race; Absence of clinical dementia English speaking Blood pressure not exceeding 150/90 mmHg, treated or untreated Weight greater than 110 lbs Normal result on liver-function test No history of ulcer disease or GI bleeding No renal insufficiency Additional Inclusion Criteria for Depressed Participants: DSM-IV criteria for Major Depressive Disorder HAM-D greater than 18 Exclusion Criteria: Known history of relevant severe drug allergy or hypersensitivity (e.g. to Citalopram or Escitalopram, and/or to celecoxib, aspirin, or other NSAIDs only for Phase 2; known demonstration of allergic-type reactions to sulfonamides); Does not speak English; Cannot give informed consent; MRI contraindications (e.g., foreign metallic implants, pacemaker); Known primary neurological disorders, such as Parkinson's disease, Alzheimer's disease, traumatic brain injury, cognitive impairment or dementia, Known severe inflammatory disease such as systemic lupus erythematosis, known autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis; Screen + for RF, ANA, HIV, Hepatitis B or C. Clinical Dementia Rating Scale score greater than 0; Diagnosis of a chronic psychiatric illness other than MDD at the discretion of the study doctor; Significant handicaps (e.g. uncorrected hearing or visual impairment, mental retardation) that would interfere with testing; Bleeding diathesis; Severe Medical problem, which in the opinion of the investigator would pose a safety risk to the subject; Clinically significant cardiovascular disease that will be assessed on a case-by-case basis. Clinically significant cardiovascular disease usually includes one or more of the following: cardiac surgery or myocardial infarction within the last 4 weeks; unstable angina; acute decompensated congestive heart failure or class IV heart failure; current significant cardiac arrhythmia or conduction disturbance, particularly those resulting in ventricular fibrillation, or causing syncope or near syncope; uncontrolled high blood pressure; QTc greater than 450msec (by history for subjects with cardiac disease); documented prior stroke; Clinically significant abnormalities on EKG. Primary AV block or Right bundle branch block are not necessarily exclusionary; Current diagnosis of cancer Current diagnosis of HIV, active Hepatitis B and/or Hepatitis C Use of an Investigational medicine within the past 30 days; Use of Coumadin, Warfarin within the past 2 months; Current treatment with psychotropic drugs or drugs that affect the CNS such as beta-blockers, mood stabilizers, antipsychotics, steroids or non-steroidal anti-inflammatory medications or other antidepressants. No subjects will be included in the study unless they have been off all psychotropics for at least 3 weeks, except in the case of fluoxetine, where 5 weeks off treatment will be required; Current alcohol or substance abuse disorder, schizophrenia or other psychotic disorder, bipolar disorder, or current OCD; Abnormal liver-function test History of ulcer disease, Chron's disease, GI bleeding or anemia Weight less than 110 lbs Renal insufficiency Any other factor that in the investigator's judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from this facility); Additional Exclusion Criteria for Depressed Subjects: 1) Active suicidality or current suicidal risk as determined by the investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yvette Sheline
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35332134
Citation
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.
Results Reference
derived

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Stress and Inflammation in Late-Life Depression

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