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

NCT03523767 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: HSC-MS-16-0496
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

Typhoid Vaccine, then Normal Saline

EXPERIMENTAL

0.5 ml of S.typhi injection, then 0.5 ml of normal saline injection

Biological: S.typhi Injection; Biological: Normal Saline Injection

Normal Saline, then Typhoid Vaccine

PLACEBO COMPARATOR

0.5 ml of normal saline injection, then 0.5 ml of S.typhi injection

Biological: S.typhi Injection; Biological: Normal Saline Injection

Interventions

S.typhi Injection BIOLOGICAL

0.5 ml of S.typhi injection

Normal Saline, then Typhoid Vaccine; Typhoid Vaccine, then Normal Saline

Normal Saline Injection BIOLOGICAL

0.5 ml of normal saline injection

Normal Saline, then Typhoid Vaccine; Typhoid Vaccine, then Normal Saline

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

Sudhakar Selvaraj

Houston, Texas, 77054, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Sudhakar Selvaraj, 7134862627

  Prinicpal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The study clinician/ nurse will be aware of the nature of the injection. The study subjects and researcher collecting/analyzing the data will remain blinded to the intervention due to the possible confounding effects of the participant expectations and researcher analyzing the data.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sudhakar Selvaraj, MBBS., DPhil (Oxon)., MRCPsych

Model Details: In this double blind 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.

Study Record Dates

• First Submitted: May 1, 2018
• First Posted: May 14, 2018
• Study Start: February 7, 2018
• Primary Completion: February 7, 2020
• Study Completion: February 7, 2020
• Last Updated: April 4, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)