Effect of Systemic Inflammation on Emotion and Cognition in Patients With Mood Disorder - A Vaccine Study
- Conditions
- Major Depressive Disorder
- Interventions
- Biological: S.typhi InjectionBiological: Normal Saline Injection
- Registration Number
- NCT03523767
- 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).
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 19
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Typhoid Vaccine, then Normal Saline S.typhi Injection 0.5 ml of S.typhi injection, then 0.5 ml of normal saline injection Normal Saline, then Typhoid Vaccine Normal Saline Injection 0.5 ml of normal saline injection, then 0.5 ml of S.typhi injection Typhoid Vaccine, then Normal Saline Normal Saline Injection 0.5 ml of S.typhi injection, then 0.5 ml of normal saline injection Normal Saline, then Typhoid Vaccine S.typhi Injection 0.5 ml of normal saline injection, then 0.5 ml of S.typhi injection
- Primary Outcome Measures
Name Time Method Change in Inflammation as indicated by cytokines baseline, 3-6 hours post-injection 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).
Change in depressed mood as indicated by Hamilton Depression Rating Scale (HAM-D) score baseline, 3-6 hours post-injection 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.
Level of prefrontal, limbic and striatal cortex activation as indicated by fMRI 3-6 hours post-injection Compare prefrontal cortex response to reward anticipation between the experimental and the control group, using fMRI
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Sudhakar Selvaraj
🇺🇸Houston, Texas, United States