Brain and Stress Study

NCT ID: NCT06044090

Last Updated: 2024-12-18

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-12

Study Completion Date

2023-12-19

Brief Summary

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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

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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 a computer task (Probabilistic Reward 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 task 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.

Conditions

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Stress, Psychological Motivation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Placebo followed by Minocycline

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.

Group Type EXPERIMENTAL

Minocycline

Intervention Type DRUG

Participants will take 2 pills of 100 mg totaling a 200 mg dose of minocycline per day.

Placebo

Intervention Type DRUG

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.

Minocycline followed by Placebo

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.

Group Type EXPERIMENTAL

Minocycline

Intervention Type DRUG

Participants will take 2 pills of 100 mg totaling a 200 mg dose of minocycline per day.

Placebo

Intervention Type DRUG

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.

Interventions

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Minocycline

Participants will take 2 pills of 100 mg totaling a 200 mg dose of minocycline per day.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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Minocin, Solodyn, Ximino, CoreMino sugar pill

Eligibility Criteria

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Inclusion Criteria

* 25-60 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)
Minimum Eligible Age

25 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Robert Wood Johnson Foundation

OTHER

Sponsor Role collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gabriella Alvarez, PhD

Role: STUDY_DIRECTOR

University of North Carolina, Chapel Hill

Keely Muscatell, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

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Howell Hall

Chapel Hill, North Carolina, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 35435644 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7551619 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23351831 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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21-3111

Identifier Type: -

Identifier Source: org_study_id