Stress and Inflammation in Late-Life Depression

NCT02389465 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 5R01MH098260-02
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; Inflammation

Keywords

Depression; Geriatric; Inflammation

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

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.

Drug: Escitalopram + Celecoxib; Drug: Escitalopram + Placebo

Interventions

Escitalopram + Celecoxib DRUG

Participants will receive celecoxib in addition to escitalopram

Experimental - treatment

Escitalopram + Placebo DRUG

Participants will receive a placebo in addition to escitalopram.

Experimental - treatment

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• DSM-IV criteria for Major Depressive Disorder
• HAM-D greater than 18

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 35332134 DERIVED

MeSH Terms

Conditions

Depression; Inflammation

Interventions

Escitalopram; Celecoxib

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Yvette Sheline, McLure Professor of Radiology, Neurology and Psychiatry
• Organization: University of Pennsylvania

sheline@pennmedicine.upenn.edu

(215) 573-0082

Study Officials

• Yvette Sheline

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2015
• First Posted: March 17, 2015
• Study Start: August 1, 2014
• Primary Completion: July 18, 2022
• Study Completion: July 18, 2022
• Last Updated: October 2, 2023
• Results First Posted: October 2, 2023

Record last verified: 2023-09

Locations

US (1)