Stress, PsychologicalPhase 4BASSNCT06044090
Brain and Stress Study
A Phase 4 study testing Minocycline in people with Stress, Psychological and Motivation, run by University of North Carolina, Chapel Hill at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 25 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Stress, Psychological, Motivation
- What is being tested?
- Minocycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Sep 2022to 19 Dec 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Neuroinflammatory Mechanisms Linking Chronic Stress to Motivational Deficits
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.
Read the 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 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
- Stress, Psychological, Motivation
- Being tested
- Minocycline, Placebo
- Medical subject headings
- Stress, Psychological
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Also called Minocin, Solodyn, Ximino, CoreMino
Participants will take 2 pills of 100 mg totaling a 200 mg dose of minocycline per day.
PlaceboDrug
Also called sugar pill
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo followed by Minocycline | Experimental | 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. Receives: Drug: Minocycline; Drug: Placebo |
| Minocycline followed by Placebo | Experimental | 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. Receives: Drug: Minocycline; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 placebo
Secondary outcomes (2)
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.
Measured: within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 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.
Measured: within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study start12 Sep 2022
- Primary completion19 Dec 2023
- Study completion19 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Stress, PsychologicalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Robert Wood Johnson Foundation
- Responsible party
- Sponsor
- Investigators
- Gabriella Alvarez, PhD, Study director, University of North Carolina, Chapel HillKeely Muscatell, PhD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06044090
- Sponsor's protocol ID
- 21-3111
- Acronym
- BASS
- Status last verified
- Apr 2024
- First submitted
- 12 Sep 2023
- Last updated
- 18 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 35435644Snaith 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.
PubMed 7551619Llerena 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.
PubMed 23351831
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroinflammatory Mechanisms Linking Chronic Stress to Motivational Deficits
- ClinicalTrials.gov ID
- NCT06044090
- Acronym / sponsor ID
- BASS / 21-3111
- Conditions
- Stress, Psychological, Motivation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Robert Wood Johnson Foundation
- Study start
- 12 Sep 2022 (actual)
- Primary completion
- 19 Dec 2023 (actual)
- Study completion
- 19 Dec 2023 (actual)
- First posted
- 21 Sep 2023 (actual)
- Results
- Posted 18 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo followed by Minocycline | Experimental | Drug: Minocycline, Drug: PlaceboIn 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. |
| Minocycline followed by Placebo | Experimental | Drug: Minocycline, Drug: PlaceboIn 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. |
Who may qualify
- Ages
- 25 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MinocyclineAlso: Minocin, Solodyn, Ximino, CoreMinoParticipants will take 2 pills of 100 mg totaling a 200 mg dose of minocycline per day. | Drug | Minocycline followed by Placebo, Placebo followed by Minocycline |
| PlaceboAlso: sugar pillA 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. | Drug | Minocycline followed by Placebo, Placebo followed by Minocycline |
Primary outcome
Change in Response Bias During the Probabilistic Reward Task
Time frame: within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 placebo
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.
2 secondary outcomes
Change in Snaith Hamilton Pleasure Scale Score
Time frame: within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 placebo
Change in Motivation and Pleasure Scale (MAPS) Score
Time frame: within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 placebo
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 35435644Kangas 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.
- Background: PubMed 7551619Snaith 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.
- Background: PubMed 23351831Llerena 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gabriella Alvarez, PhD study director
University of North Carolina, Chapel Hill
Keely Muscatell, PhD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Minocycline in people with Stress, Psychological and Motivation, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Response Bias During the Probabilistic Reward Task (time frame: within approximately 24 hours after the final dose; Day 6 minocycline to Day 6 placebo). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06044090, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024; AzTrials last refreshed its copy on 27 Oct 2026.