Effect of Systemic Inflammation on Emotion and Cognition in Patients With Mood Disorder - A Vaccine Study

The purpose of this pilot study is to investigate and compare the effect of a mild inflammatory stimulus (typhoid vaccine) on immune response, mood and cognition in healthy volunteers compared to patients with history Major Depressive Disorder (MDD) (not currently depressed and no symptoms of depression in the past 6 months).

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Biological: S.typhi Injection; Biological: Normal Saline Injection

Detailed Description

Study design: In this double blind randomized crossover design, each participant will receive saline injection or typhoid vaccine injection at the first study visit, and will then receive the other injection at the second study visit. All participants will undergo study procedures (clinical and imaging) in two separate sessions after each injection given at least 7 days apart (within 10-14 days).

Baseline blood samples will be taken and vital signs will be measured. Participants will be asked to complete the mood questionnaires and computerized reward tasks. Then, injections of normal saline will be administered intramuscularly in the deltoid muscle. At 1.5h, 3h, 4h and 6h after the injection, the subjects will complete the mood questionnaires and vital signs will be assessed. The computer based task will be repeated at 3h.

Between3h and 6h after the injection blood samples will be collected for cytokines measurement. At 4h, a structural magnetic resonance imaging (MRI), and Functional magnetic resonance imaging (fMRI) will be done.

Follow up visits/calls with the patients will be set to check their physical and mood status.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77054
      • Sudhakar Selvaraj

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers, male or female; aged 18-65
• Subjects with history of Major depression (currently asymptomatic - symptom free for more than 6 months)
• Medication free, if not feasible being on antidepressants will be allowed

Exclusion Criteria:

• Volunteers who received this vaccine within 3 years or any other vaccine within 3 months
• Patients with existing inflammatory conditions (connective tissue disorder, autoimmune conditions, neoplastic disease, chronic infections, etc.)
• Patients with acute viral or bacterial infection
• Hospitalized patients
• Patients in acute phase of illness
• Current active medical condition that affect brain anatomy, neurochemistry, or function, e.g. liver insufficiency, kidney insufficiency, cardiovascular problems, systemic infections, cancer, hypothyroidism, auto-immune diseases, and any brain disorder (seizure disorder, stroke, dementia, degenerative neurologic diseases)
• History of any brain diseases, including seizures, stroke, meningitis, encephalitis, dementia, degenerative brain diseases, and serious head injury with loss of consciousness
• Family history of hereditary neurologic disorder
• Floating metallic objects in the body
• Pregnancy
• Exposure to regular use of anti-inflammatory drugs in the last one month
• Excessive exercise, consumption of caffeinated beverages or alcohol, high-fat meals 12 hours before testing
• History of tobacco, alcohol, or drug abuse or dependence.
• History of allergic reaction to vaccination or serious allergic reaction to shellfish or egg allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Typhoid Vaccine, then Normal Saline; 0.5 ml of S.typhi injection, then 0.5 ml of normal saline injection	Biological: S.typhi Injection; 0.5 ml of S.typhi injection; Biological: Normal Saline Injection; 0.5 ml of normal saline injection
Placebo Comparator: Normal Saline, then Typhoid Vaccine; 0.5 ml of normal saline injection, then 0.5 ml of S.typhi injection	Biological: S.typhi Injection; 0.5 ml of S.typhi injection; Biological: Normal Saline Injection; 0.5 ml of normal saline injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Inflammation as indicated by cytokines	To compare proinflammatory cytokines (e.g. IL-6, TNF-α, etc) concentration between the experimental (receiving S.typhi vaccine) and the control group (receiving normal saline).	baseline, 3-6 hours post-injection
Change in depressed mood as indicated by Hamilton Depression Rating Scale (HAM-D) score	To compare the severity of mood symptoms (as scored on the Hamilton Depression Rating Scale) between the experimental and the control group. A score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity of depressive symptoms. Scores range from 0-53.	baseline, 3-6 hours post-injection
Level of prefrontal, limbic and striatal cortex activation as indicated by fMRI	Compare prefrontal cortex response to reward anticipation between the experimental and the control group, using fMRI	3-6 hours post-injection

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Sudhakar Selvaraj, 7134862627, Prinicpal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2018
• Primary Completion (Actual): February 7, 2020
• Study Completion (Actual): February 7, 2020

Study Registration Dates

• First Submitted: May 1, 2018
• First Submitted That Met QC Criteria: May 1, 2018
• First Posted (Actual): May 14, 2018

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Depressive Disorder; Inflammation; Mood Disorders; Depressive Disorder, Major
• Other Study ID Numbers: HSC-MS-16-0496

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No