Brain and Stress Study

Stress, Psychological Clinical Trial

— BASS  

Official title:

Neuroinflammatory Mechanisms Linking Chronic Stress to Motivational Deficits

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06044090
• Other study ID #: 21-3111
• Status: Completed
• Phase: Phase 4
• Start date: September 12, 2022
• Est. completion date: December 19, 2023

Study information

• Verified date: April 2024
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 19, 2023
• Est. primary completion date: December 19, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 50 Years

Eligibility

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)

Related Conditions & MeSH terms

• Motivation
• Stress, Psychological

Intervention

Drug:
• Minocycline
Participants will take 2 pills of 100 mg totaling a 200 mg dose of minocycline per day.
• Placebo
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.

Locations

Country	Name	City	State
United States	Howell Hall	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Robert Wood Johnson Foundation

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 placebo
Secondary	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.	within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 placebo
Secondary	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.	within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 placebo