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Brain and Stress Study (BASS)

Primary Purpose

Stress, Psychological, Motivation

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Minocycline
Placebo
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Stress, Psychological

Eligibility Criteria

25 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 25-50 years old Unemployed (working less than 20 hours per week) Have been unemployed for at least 6 months Seeking employment Having trouble finding a job (i.e., actively seeking and applying for jobs but not successful in landing a job) Reports greater than 5 points on Job Stress Items Regular access to a mobile phone Exclusion Criteria: Self-reported physical illnesses: diabetes, cardiovascular diseases, high blood pressure, inflammatory bowel diseases, rheumatoid arthritis, asthma, autoimmune disease, Crohn's disease, ulcerative colitis, lupus neurological conditions (e.g., Traumatic Brain Injury, stroke) pregnant (as measured by urine pregnancy screen) or breastfeeding current use of psychotropic medications Current regular recreational drug or alcohol use (i.e., 4 or more times per week) chronic diseases that significantly impact inflammatory markers (e.g., cancer) known allergies or hypersensitivities to tetracycline antibiotics, aspirin or other NSAIDs current antibiotic use regular use of steroidal or non-steroidal anti-inflammatory medications (i.e., 2 or more times a week)

Sites / Locations

  • Howell HallRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Placebo followed by Minocycline

Minocycline followed by Placebo

Arm Description

In this arm, participants will take a 5-day course of placebo-control pills and then a 5-day course of 200 mg of minocycline. Sessions will be separated by a minimum washout period of 14 days.

In this arm, participants will take a 5-day course of 200 mg of minocycline and then a 5-day course of placebo-control pills. Sessions will be separated by a minimum washout period of 14 days.

Outcomes

Primary Outcome Measures

Change in response bias during the Probabilistic Reward Task
The aim of Probabilistic Reward Task (PRT) is to win as much money as possible by correctly identifying the presence of a short versus long mouth on a cartoon face. The task aims to produce a response bias toward the mouth length that is more often positively reinforced. The response bias score is a ratio of the number of times the participant chooses the high reward versus the low reward stimulus. Scores range from -1 to +1, with a positive score indicating a stronger bias toward the high reward stimulus. The change in response bias is calculated by subtracting response bias during the PRT in the placebo condition from the minocycline condition. This difference measures an individual's change in reward behavior after a 5-day dosage of an anti-neuroinflammatory agent.

Secondary Outcome Measures

Change in Snaith Hamilton Pleasure Scale score
The Snaith-Hamilton Pleasure Scale (SHAPS) is a tool to assess symptoms of reduced motivation. The SHAPS uses 14 questions, each rated on a Likert scale of 1-4. The total score on the scale ranges from 14-56, with lower scores reflecting lower motivation. Scores will be compared across conditions to determine whether motivation changes in the minocycline condition as compared to the placebo.
Change in Motivation and Pleasure Scale (MAPS) score
The Motivation and Pleasure Scale (MAP) will be used to capture self-reported aspects of reduced motivation. The scale uses 18 questions, each rated on a Likert scale of 0-4. The total score on the scale ranges from 0-72, with lower scores reflecting lower motivation. Scores will be compared across conditions to determine whether motivation changes in the minocycline condition as compared to the placebo.

Full Information

First Posted
September 12, 2023
Last Updated
September 12, 2023
Sponsor
University of North Carolina, Chapel Hill
Collaborators
Robert Wood Johnson Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT06044090
Brief Title
Brain and Stress Study
Acronym
BASS
Official Title
Neuroinflammatory Mechanisms Linking Chronic Stress to Motivational Deficits
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 12, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
Robert Wood Johnson Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Motivational deficits such as anhedonia are core to several psychiatric disorders and underlie significant functional impairment. This double-blind, placebo-controlled crossover trial of minocycline, an anti-[neuro]inflammatory agent, examines links between chronic stress and responses to a reward-related motivation task. It will evaluate the effects of pharmacologically attenuating neuroinflammation on behavioral responses to a reward-related motivation task in individuals experiencing unemployment. Understanding the effects of neuroinflammation on reward function among individuals experiencing chronic stress represents a critical first step in identifying novel neuroimmune targets for future clinical trials.
Detailed Description
This study seeks to conduct translational work that extends rich preclinical findings to the clinical domain to validate whether neuroinflammatory dysregulation is strongly tied to anhedonia. This project addresses critical gaps in the scientific literature by recruiting a chronically stressed sample of individuals-employment seeking individuals who report significant stress-- and will use an experimental therapeutics approach to attenuate neuroinflammation and assess behavioral changes in motivation. One major obstacle in understanding how neuroinflammation influences motivation involves technological challenges such that conventional approaches are invasive, expensive, and/or lacking specificity. Although static levels of neuroinflammation in humans have been measured via cross sectional studies, capturing behavioral shifts following experimental manipulation has not been done. This gap limits the ability to develop a more precise understanding of how neuroinflammation causes motivational deficits in humans. The proposed project will employ a mechanistic clinical trial of the anti-[neuro]inflammatory agent, minocycline, to address these limitations. In animal models, minocycline has attenuated the deleterious effects of neuroinflammation on neurogenesis, long-term potentiation, and neuronal survival. This study will extend research to humans to examine whether links between neuroinflammation and behavioral responses to a reward-related motivation task differ among chronically stressed individuals taking minocycline and the placebo control. The proposed project will provide preliminary evidence for potential neural targets that have relevance for motivational deficits due to neuroinflammation. Once screening is complete, participants will come to UNC to complete quality-of-life surveys, learn about the full study schedule, and receive the first dose of medication. This visit will last about 90 minutes. Participants will be asked to participate in two medication periods, meaning they will take both minocycline (antibiotic medication) for 5-days, and an inactive substance (placebo sugar pill) for 5-days. This will investigate whether there are changes in their responses to negative and positive information. After taking the first medication for five days, participants will come in to complete computer tasks (Probabilistic Reward Task, Negative Emotion Dot Probe, and Threatening Visual Search Task) and some follow-up surveys (Snaith-Hamilton Pleasure Scale and Motivation and Pleasure Scale). This visit will last about 90 minutes. Participants will then get at least a 2-week break before taking the second medication for five days. Then, they will come back for another 90-minute visit to complete the same computer tasks and follow-up surveys. The total study duration including the break is about one month. The total time in study sessions on campus over the month will be 4.5 hours.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stress, Psychological, Motivation

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
38 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo followed by Minocycline
Arm Type
Experimental
Arm Description
In this arm, participants will take a 5-day course of placebo-control pills and then a 5-day course of 200 mg of minocycline. Sessions will be separated by a minimum washout period of 14 days.
Arm Title
Minocycline followed by Placebo
Arm Type
Experimental
Arm Description
In this arm, participants will take a 5-day course of 200 mg of minocycline and then a 5-day course of placebo-control pills. Sessions will be separated by a minimum washout period of 14 days.
Intervention Type
Drug
Intervention Name(s)
Minocycline
Other Intervention Name(s)
Minocin, Solodyn, Ximino, CoreMino
Intervention Description
Participants will take 2 pills of 100 mg totaling a 200 mg dose of minocycline per day.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
sugar pill
Intervention Description
A placebo is a sugar pill that has no therapeutic effect and will be administered orally. Participants will receive 2 placebo tablets matching the Minocycline tablets daily for 5 days.
Primary Outcome Measure Information:
Title
Change in response bias during the Probabilistic Reward Task
Description
The aim of Probabilistic Reward Task (PRT) is to win as much money as possible by correctly identifying the presence of a short versus long mouth on a cartoon face. The task aims to produce a response bias toward the mouth length that is more often positively reinforced. The response bias score is a ratio of the number of times the participant chooses the high reward versus the low reward stimulus. Scores range from -1 to +1, with a positive score indicating a stronger bias toward the high reward stimulus. The change in response bias is calculated by subtracting response bias during the PRT in the placebo condition from the minocycline condition. This difference measures an individual's change in reward behavior after a 5-day dosage of an anti-neuroinflammatory agent.
Time Frame
within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 placebo
Secondary Outcome Measure Information:
Title
Change in Snaith Hamilton Pleasure Scale score
Description
The Snaith-Hamilton Pleasure Scale (SHAPS) is a tool to assess symptoms of reduced motivation. The SHAPS uses 14 questions, each rated on a Likert scale of 1-4. The total score on the scale ranges from 14-56, with lower scores reflecting lower motivation. Scores will be compared across conditions to determine whether motivation changes in the minocycline condition as compared to the placebo.
Time Frame
within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 placebo
Title
Change in Motivation and Pleasure Scale (MAPS) score
Description
The Motivation and Pleasure Scale (MAP) will be used to capture self-reported aspects of reduced motivation. The scale uses 18 questions, each rated on a Likert scale of 0-4. The total score on the scale ranges from 0-72, with lower scores reflecting lower motivation. Scores will be compared across conditions to determine whether motivation changes in the minocycline condition as compared to the placebo.
Time Frame
within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 placebo

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 25-50 years old Unemployed (working less than 20 hours per week) Have been unemployed for at least 6 months Seeking employment Having trouble finding a job (i.e., actively seeking and applying for jobs but not successful in landing a job) Reports greater than 5 points on Job Stress Items Regular access to a mobile phone Exclusion Criteria: Self-reported physical illnesses: diabetes, cardiovascular diseases, high blood pressure, inflammatory bowel diseases, rheumatoid arthritis, asthma, autoimmune disease, Crohn's disease, ulcerative colitis, lupus neurological conditions (e.g., Traumatic Brain Injury, stroke) pregnant (as measured by urine pregnancy screen) or breastfeeding current use of psychotropic medications Current regular recreational drug or alcohol use (i.e., 4 or more times per week) chronic diseases that significantly impact inflammatory markers (e.g., cancer) known allergies or hypersensitivities to tetracycline antibiotics, aspirin or other NSAIDs current antibiotic use regular use of steroidal or non-steroidal anti-inflammatory medications (i.e., 2 or more times a week)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gabriella Alvarez, PhD
Phone
(919) 843-9113
Email
alvarezg@unc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Keely Muscatell, PhD
Phone
(919) 843-9113
Email
kmuscatell@unc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gabriella Alvarez, PhD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Keely Muscatell, PhD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
Howell Hall
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charlotte Boettiger, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
IPD Sharing Time Frame
beginning 9 and continuing for 36 months following publication
IPD Sharing Access Criteria
Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.
Citations:
PubMed Identifier
35435644
Citation
Kangas BD, Der-Avakian A, Pizzagalli DA. Probabilistic Reinforcement Learning and Anhedonia. Curr Top Behav Neurosci. 2022;58:355-377. doi: 10.1007/7854_2022_349.
Results Reference
background
PubMed Identifier
7551619
Citation
Snaith RP, Hamilton M, Morley S, Humayan A, Hargreaves D, Trigwell P. A scale for the assessment of hedonic tone the Snaith-Hamilton Pleasure Scale. Br J Psychiatry. 1995 Jul;167(1):99-103. doi: 10.1192/bjp.167.1.99.
Results Reference
background
PubMed Identifier
23351831
Citation
Llerena K, Park SG, McCarthy JM, Couture SM, Bennett ME, Blanchard JJ. The Motivation and Pleasure Scale-Self-Report (MAP-SR): reliability and validity of a self-report measure of negative symptoms. Compr Psychiatry. 2013 Jul;54(5):568-74. doi: 10.1016/j.comppsych.2012.12.001. Epub 2013 Jan 22.
Results Reference
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Brain and Stress Study

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