Memory Impairment
Conditions
Brief summary
The purpose of this study is to examine whether vilazodone attenuates the memory and mood effects of corticosteroids on the human hippocampus in 24 healthy controls.
Detailed description
In animals and humans, stress and corticosteroid excess are associated with changes in hippocampal structure and functioning. These findings have important implications to the millions of patients taking prescription corticosteroids and to patients with major depressive disorder or bipolar disorder who have elevated cortisol levels and memory impairment. The investigators believe that vilazodone may be a medication that can block the effects of hydrocortisone on the human hippocampus. The investigators propose to examine whether vilazodone attenuates the effects of corticosteroids in a randomized, double-blind, placebo-controlled pilot study using a within-subject crossover design.
Interventions
DRUGVilazodone
Participants will be randomized to either vilazodone or placebo titrated as follows: 10 mg x 7 days, 20 mg x 7 days and 40 mg x 5 days.
DRUGPlacebo
DRUGHydrocortisone
Participants receive 160 mg x 4 days after vilazodone or placebo pre-treatment
Sponsors
Forest Laboratories
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy men and women age 18-50 years * Education of ≥ 12 years and baseline RAVLT total words recalled score ≥ 35 (normal baseline memory) * BMI between 18.5-30 (not underweight or obese)
Exclusion criteria
* History of major psychiatric illness defined as major depressive disorder, bipolar disorder, posttraumatic stress disorder, panic disorder, schizoaffective disorder, schizophrenia, eating disorders, or drug/alcohol abuse/dependence or current tobacco use * History of neurological disorders including seizures, brain surgery, multiple sclerosis, Parkinson's disease * Taking CNS-acting medications within 30 days of study * History of allergic reaction or medical contraindication to vilazodone or hydrocortisone * Significant medical conditions (e.g., myocardial infarction, cancer, diabetes) * Vulnerable population including pregnant or nursing women, the incarcerated, and severe cognitive disorders * Baseline HRSD (Hamilton Rating Scale for Depression) \> 7 or current suicidal ideation or history of suicide attempt * History of systemic Corticosteroid (CS) use or recent (past 6 months) inhaled CS use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline RAVLT (Rey Auditory Verbal Learning Test) Total T-Score at Day 19 | Baseline and Day 19 | The Rey Auditory Verbal Learning Test (RAVLT) measures verbal or declarative learning and memory. The test consists of 15 nouns read aloud for five consecutive trials with each trial followed by a free-recall trial. Following the fifth trial, an interference list of 15 different words is presented followed by a free-recall trial of that list. Delayed recall of the first list is tested immediately following the interference list and after a 20-minute delay. Equivalent, alternative versions (different words) were used to minimize practice or learning effects from repeated administration. The raw scores (number of words correct across trials 1-5) are converted to standardized T-scores (M=50; SD=10). This score is used to determine the participant's performance in relation to norm-referenced expectations based on age and sex. Higher score reflects better performance, and the values reflect scores at baseline minus the scores at Day 19. |
Countries
United States
Participant flow
Recruitment details
24 participants with at least one post-baseline visit were recruited at our research clinic in Dallas, TX and included for analysis.
Pre-assignment details
Healthy control participants without any history of major psychiatric illness, drug/alcohol abuse/dependence, history of neurological disorders, or significant medical conditions were included.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants who were randomized to receive either Vilazodone and hydrocortisone or placebo and hydrocortisone. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 24 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 2 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Change From Baseline RAVLT (Rey Auditory Verbal Learning Test) Total T-Score at Day 19
The Rey Auditory Verbal Learning Test (RAVLT) measures verbal or declarative learning and memory. The test consists of 15 nouns read aloud for five consecutive trials with each trial followed by a free-recall trial. Following the fifth trial, an interference list of 15 different words is presented followed by a free-recall trial of that list. Delayed recall of the first list is tested immediately following the interference list and after a 20-minute delay. Equivalent, alternative versions (different words) were used to minimize practice or learning effects from repeated administration. The raw scores (number of words correct across trials 1-5) are converted to standardized T-scores (M=50; SD=10). This score is used to determine the participant's performance in relation to norm-referenced expectations based on age and sex. Higher score reflects better performance, and the values reflect scores at baseline minus the scores at Day 19.
Time frame: Baseline and Day 19
Population: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vilazodone and Hydrocortisone | Change From Baseline RAVLT (Rey Auditory Verbal Learning Test) Total T-Score at Day 19 | -3 T-score | Standard Deviation 12.48 |
| Placebo and Hydrocortisone | Change From Baseline RAVLT (Rey Auditory Verbal Learning Test) Total T-Score at Day 19 | 0 T-score | Standard Deviation 7.98 |