Vilazodone for Corticosteroid-Induced Memory Impairment

• ClinicalTrials.gov Identifier: NCT01828515
• Recruitment Status: Completed
• First Posted: April 10, 2013
• Results First Posted: July 5, 2018
• Last Update Posted: April 11, 2019
• Sponsor: University of Texas Southwestern Medical Center
• Collaborator: Forest Laboratories
• Information provided by (Responsible Party): Sherwood Brown, MD, PhD, University of Texas Southwestern Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Memory Impairment	Drug: Vilazodone; Drug: Placebo; Drug: Hydrocortisone	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Vilazodone for Corticosteroid-Induced Memory Impairment
• Study Start Date: December 2012
• Actual Primary Completion Date: April 2014
• Actual Study Completion Date: April 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vilazodone and Hydrocortisone, then Placebo and 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.	Drug: Vilazodone; 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.; Other Name: Viibryd; Drug: Placebo; Drug: Hydrocortisone; Participants receive 160 mg x 4 days after vilazodone or placebo pre-treatment
Experimental: Placebo and Hydrocortisone, then Vilazodone and 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.	Drug: Vilazodone; 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.; Other Name: Viibryd; Drug: Placebo; Drug: Hydrocortisone; Participants receive 160 mg x 4 days after vilazodone or placebo pre-treatment

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline RAVLT (Rey Auditory Verbal Learning Test) Total T-Score at Day 19 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Texas

UT Southwestern Medical Center

Dallas, Texas, United States, 75390

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Forest Laboratories

Investigators

• Principal Investigator: E. Sherwood Brown, M.D., Ph.D.; UT Southwestern Medical Center

More Information

• Responsible Party: Sherwood Brown, MD, PhD, Professor, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT01828515
• Other Study ID Numbers: 082012-082
• First Posted: April 10, 2013
• Results First Posted: July 5, 2018
• Last Update Posted: April 11, 2019
• Last Verified: March 2019

Additional relevant MeSH terms:

Memory Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Hydrocortisone; Vilazodone Hydrochloride; Anti-Inflammatory Agents; Antidepressive Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists