Exploratory Study on the Mood and Cytokine Levels in Female Healthy Participants and Major Depressive Disorder Patients
Exploratory Study on the Mood and Cytokine Levels in Female Healthy Participants and Major Depressive Disorder Patients
The purpose of this study is to explore the effect of an inflammatory and a psychosocial
 stressor and the combination thereof on mood in healthy young and elderly participants and
 patients with Major Depressive Disorder (MDD).
This is a 2-way crossover (method used to switch patients from one treatment arm to another
 in a clinical study), randomized (the study medication is assigned by chance),
 placebo-controlled (an inactive substance that is compared with a study medication to test
 whether the medication has a real effect in a clinical study) study in 3 cohorts (group of
 individuals with similar characteristics) ie, 18 healthy young female participants; 18
 healthy elderly female participants; 18 female patients with a past history of MDD.
 Participants will be randomized to 1 of 6 possible treatment groups: Group 1: Treatment AB,
 Group 2: Treatment BA, Group 3: Treatment AC, Group 4: Treatment CA, Group 5: Treatment AD,
 Group 6: Treatment DA, where Treatment A is placebo vaccination, Treatment B is typhoid
 vaccination, Treatment C is psychosocial stress (Trier Social Stress Test [TSST]) followed by
 placebo vaccination, and Treatment D is psychosocial stress (TSST) followed by typhoid
 vaccination. Participants from each of the 3 cohorts will be randomized to these 6 treatment
 groups. In all the 6 groups the 1st treatment comes under Period 1 and 2nd treatment under
 Period 2 (eg, In Group 1: Treatment A [Period 1] and Treatment B [Period 2]) and there will
 be a minimally 7- and maximally 14- day washout period (period when no treatment is received)
 between the study periods. The study will consist of an eligibility screening examination
 (from 21 to 2 days prior to Day 1 of Period 1); a run-in visit (only prior to Period 1) in
 which eligible participants will be briefly explained about the cognitive test battery and
 immediately thereafter the baseline of cognitive function will be measured via these tests; 2
 single-blind (a clinical study in which the person giving the treatment, but not the patient,
 knows which treatment the patient is receiving) treatment periods (2-way crossover); and a
 follow-up examination by phone (approximately 7 to 14 days after last treatment [Period 2]).
 For each participant, the maximal study duration will not exceed 8 weeks.
Inclusion criteria:

 -  Has body mass index (BMI) [weight in kilograms / (height in meters x height in
 meters)] between 18 and 30 kg/m2

 -  For young healthy participants: female, 25 to 45 years of age; elderly healthy
 participants: female: ≥ 65 years of age & with baseline C-reactive protein (CRP) > 5
 mg/mL; (partially) remitted MDD patients: female, 25 to 45 years of age

 -  Inclusion criteria specific for patients with MDD: -Patients with a history (within 24
 months) of MDD must have a Montgomery-Asberg Depression Rating Scale (MADRS) total
 score < 15 and symptom remission (temporary absence of disease symptoms) relative to
 the acute episode must have been present for at least 3 months

 Exclusion Criteria:

 -  Has a current Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) axis I
 diagnosis (other than MDD)

 -  Has recently experienced a psychosocial stressor within 6 months

 -  Has acute symptoms of suicidality (the likelihood of an individual completing suicide)

 -  Has a DSM-IV diagnosis of substance abuse or dependence within 6 months prior to
 screening evaluation

 -  Has been exposed to an experimental medication or experimental medical device within
 90 days before screening

 -  Has a serology (scientific study of blood serum and other bodily fluids) positive for
 hepatitis B surface antigen (HBsAg), hepatitis C antibodies or HIV antibodies at
 screening

 -  Has been exposed to typhoid or typhoid vaccine within 5 years before screening

 -  Has been prior exposed to the Trier Social Stress Test (TSST)

 -  Has received electroconvulsive therapy (shock therapy) within 3 months before
 screening

 -  Has been involuntarily committed to psychiatric hospitalization

 -  Has donated 1 or more units (approximately 450 mL) of blood or had an acute loss of an
 equivalent amount of blood within 90 days prior to study medication administration