Vilazodone for Corticosteroid-Induced Memory Impairment

Phase 2

Completed

Conditions: Memory Impairment

Interventions: Drug: Vilazodone
Drug: Placebo
Drug: Hydrocortisone

Registration Number: NCT01828515

Lead Sponsor: University of Texas Southwestern Medical Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Vilazodone and Hydrocortisone, then Placebo and Hydrocortisone	Vilazodone	Vilazodone titrated to 10 mg x 7 days, 20 mg x 7 days and 40 mg x 5 days (19 days) and hydrocortisone 160 mg x 4 days (days 16-19) following vilazodone pre-treatment. After a 23 day medication washout the procedure will be repeated using placebo daily for 19 days and hydrocortisone 160 mg x 4 days (days 16-19) following placebo pre-treatment.
Placebo and Hydrocortisone, then Vilazodone and Hydrocortisone	Placebo	Placebo daily for 19 days and hydrocortisone 160 mg x 4 days (days 16-19) following placebo pre-treatment. After a 23 day medication washout the procedure will be repeated using Vilazodone titrated to 10 mg x 7 days, 20 mg x 7 days and 40 mg x 5 days (19 days) and hydrocortisone 160 mg x 4 days (days 16-19) following vilazodone pre-treatment.
Vilazodone and Hydrocortisone, then Placebo and Hydrocortisone	Placebo	Vilazodone titrated to 10 mg x 7 days, 20 mg x 7 days and 40 mg x 5 days (19 days) and hydrocortisone 160 mg x 4 days (days 16-19) following vilazodone pre-treatment. After a 23 day medication washout the procedure will be repeated using placebo daily for 19 days and hydrocortisone 160 mg x 4 days (days 16-19) following placebo pre-treatment.
Vilazodone and Hydrocortisone, then Placebo and Hydrocortisone	Hydrocortisone	Vilazodone titrated to 10 mg x 7 days, 20 mg x 7 days and 40 mg x 5 days (19 days) and hydrocortisone 160 mg x 4 days (days 16-19) following vilazodone pre-treatment. After a 23 day medication washout the procedure will be repeated using placebo daily for 19 days and hydrocortisone 160 mg x 4 days (days 16-19) following placebo pre-treatment.
Placebo and Hydrocortisone, then Vilazodone and Hydrocortisone	Hydrocortisone	Placebo daily for 19 days and hydrocortisone 160 mg x 4 days (days 16-19) following placebo pre-treatment. After a 23 day medication washout the procedure will be repeated using Vilazodone titrated to 10 mg x 7 days, 20 mg x 7 days and 40 mg x 5 days (19 days) and hydrocortisone 160 mg x 4 days (days 16-19) following vilazodone pre-treatment.
Placebo and Hydrocortisone, then Vilazodone and Hydrocortisone	Vilazodone	Placebo daily for 19 days and hydrocortisone 160 mg x 4 days (days 16-19) following placebo pre-treatment. After a 23 day medication washout the procedure will be repeated using Vilazodone titrated to 10 mg x 7 days, 20 mg x 7 days and 40 mg x 5 days (19 days) and hydrocortisone 160 mg x 4 days (days 16-19) following vilazodone pre-treatment.

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures