Vilazodone for Corticosteroid-Induced Memory Impairment

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01828515
• Collaborator: Forest Laboratories (Industry)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 16
• Patients Per Site Per Month: 1.5

Study Details

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
• 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: Dec 1, 2012
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 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 Names: 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 Names: 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 [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

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• 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: Apr 10, 2013
• Last Update Posted: Apr 11, 2019
• Last Verified: Mar 1, 2019

• Additional relevant MeSH terms: Memory Disorders; Hydrocortisone; Vilazodone Hydrochloride

Study Results

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 Detail	Healthy control participants without any history of major psychiatric illness, drug/alcohol abuse/dependence, history of neurological disorders, or significant medical conditions were included.

Arm/Group Title	Vilazodone and Hydrocortisone,Then Placebo and Hydrocortisone	Placebo and Hydrocortisone, Then Vilazodone and Hydrocortisone
Arm/Group Description	Vilazodone was initiated at 10 mg/day for 7 days and increased to 20 mg/day for 7 days. After that time an additional increase to 40 mg/day for 5 days (totaling 19 days). On the 2nd day of the 40 mg a day portion, 160 mg of hydrocortisone/day was given for 4 days. After a washout period of 23 days, placebo was given for 19 days and hydrocortisone was given for 4 days.	Placebo was given for 19 days and hydrocortisone was given for 4 days. After a washout period of 23 days, Vilazodone was initiated at 10 mg/day for 7 days and increased to 20 mg/day for 7 days. After that time an additional increase to 40 mg/day for 5 days (totaling 19 days). On the 2nd day of the 40 mg a day portion, 160 mg of hydrocortisone/day was given for 4 days.
Period Title: First Intervention (19 Days)
STARTED	13	11
COMPLETED	11	9
NOT COMPLETED	2	2
Period Title: First Intervention (19 Days)
STARTED	11	9
COMPLETED	6	8
NOT COMPLETED	5	1
Period Title: First Intervention (19 Days)
STARTED	6	8
COMPLETED	6	5
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Participants who were randomized to receive either Vilazodone and hydrocortisone or placebo and hydrocortisone.
Overall Participants	24
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	24 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	10 41.7%
Male	14 58.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 29.2%
Not Hispanic or Latino	17 70.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 8.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 8.3%
White	18 75%
More than one race	2 8.3%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline RAVLT (Rey Auditory Verbal Learning Test) Total T-Score at Day 19
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.

Arm/Group Title	Vilazodone and Hydrocortisone	Placebo and Hydrocortisone
Arm/Group Description	Vilazodone was initiated at 10 mg/day for 7 days and increased to 20 mg/day for 7 days. After that time an additional increase to 40 mg/day for 5 days (totaling 19 days). On the 2nd day of the 40 mg a day portion, 160 mg of hydrocortisone/day was given for 4 days.	Placebo was given for 19 days and hydrocortisone was given for 4 days.
Measure Participants	14	14
Mean (Standard Deviation) [T-score]	-3 (12.48)	0 (7.98)

Adverse Events

Time Frame	Adverse events were collected during the study between baseline and end of study procedures (after 2 complete cycles of treatment) or an average of 2 months.
Adverse Event Reporting Description	Adverse events were assessed by a weekly questionnaire at each appointment.
Arm/Group Title	Vilazodone and Hydrocortisone		Placebo and Hydrocortisone
Arm/Group Description	Vilazodone was initiated at 10 mg/day for 7 days and increased to 20 mg/day for 7 days. After that time an additional increase to 40 mg/day for 5 days (totaling 19 days).		Placebo group received medication in identical color/sizes as the Vilazodone group. Placebo was given for 19 days.
All Cause Mortality
	Vilazodone and Hydrocortisone		Placebo and Hydrocortisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)
Serious Adverse Events
	Vilazodone and Hydrocortisone		Placebo and Hydrocortisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Vilazodone and Hydrocortisone		Placebo and Hydrocortisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/24 (8.3%)		0/24 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	1/24 (4.2%)	1	0/24 (0%)	0
Vascular disorders
Varicocele	1/24 (4.2%)	1	0/24 (0%)	0

Limitations/Caveats

The sample size was modest and attrition rate was high; The study also lacked neuroimaging or other biomarkers to correlate changes in memory; Study drug adherence was only assessed with pill counts not with metered dosing counts or blood levels.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.