Role Of Sensitivity to neuroEndocrine Systems in Social Decisions

Phase 4

Withdrawn

• Conditions: Borderline Personality Disorder
• Interventions: Drug: Placebo; Drug: Hydrocortisone; Dietary Supplement: Yohimbine

• Registration Number: NCT06018727
• Lead Sponsor: University of North Carolina, Chapel Hill

Brief Summary

The purpose of this research study is to investigate how personality traits and neuroendocrine systems relate to decision-making patterns in individuals 18-45 years old. The main question it aims to answer is how neuroendocrine activity impacts decision-making.

This study has two components. First, there will be an online session that participants complete to consent into the study, complete self-report surveys and a cognitive assessment, and confirm their eligibility for the second part of the study. If eligible to continue, participants will complete one in-person experiment session, during which they will complete self-report measures and a decision-making task. During the in-person session, participants will be randomly assigned (like flipping a coin) to ingest either a placebo (non-active) or the combination of hydrocortisone and yohimbine.

Detailed Description

This study has two components. First, there will be a 60 minute online session. During this session, participants will first be asked to complete the informed consent process, a demographics and contact form, a series of questionnaires, a working memory assessment, and a HIPAA authorization. Researchers will also conduct a brief interview about the participant's medical history (including questions about mood, personality, and symptoms of borderline personality disorder), which is used to assess eligibility for participation in the study.

If eligible to continue, participants will complete one 90 minute in-person experiment session. During the in-person session, participants will be randomly assigned (like flipping a coin) to ingest either a placebo (non-active) or the combination of hydrocortisone and yohimbine. Ingesting hydrocortisone and yohimbine will increase participants' neuroendocrine (hormone) levels, which naturally become elevated in response to stress. After ingesting either the placebo or hydrocortisone plus yohimbine, participants will complete a series of questionnaires on a computer as well as an online decision-making task. While completing the computer task, participants' heart rate and pupil size activity will be monitored using an ECG monitor and an eye tracker. Three salivary samples will also be collected during this session: one immediately before participants ingest the placebo or hydrocortisone/yohimbine combination and two immediately before and after participants complete the computer game. These salivary samples will be collected, stored, then assayed, a process that allows us to measure participants' cortisol levels, a hormone important for the body's stress response.

Study Timeline

• Status Verified: 2023-08
• Study First Submitted: 2023-08-22
• Study First Submitted QC: 2023-08-28
• Study First Posted: 2023-08-31
• Last Update Submitted: 2024-06-03
• Last Update Posted: 2024-06-05
• Study Start: 2024-07
• Primary Completion: 2025-07
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Borderline Personality Disorder (BPD) group:

• Score of 38 or higher on PAI-BOR

• Participants in the BPD group will be primarily recruited from the two DEPENd lab studies that maintain large samples of BPD participants. To ensure maximal similarity between BPD participants recruited from other DEPENd lab studies and BPD participants recruited through other recruitment sources, the investigators will use the same criteria for the BPD group in the ROSES study as the criteria used in the other DEPENd lab studies. BPD participants in the two DEPENd lab studies from which the investigators will be recruiting must meet the following criteria:

  1. 3+ BPD symptoms, one of which must be affective instability, per clinical interview
  2. Participants must score at least 80 on the Reynolds Intellectual Screening Test (RIST).

Matched Control (MC) group:

• Score of 12 or lower on PAI-BOR
• Score below 50th percentile on WHODAS

Combined Inclusion Criteria:

• Ages 18-45
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and lifestyle considerations and availability for the duration of the study
• Willingness to participate in all components of the study
• Access to necessary resources for participating in the virtual Session 1 (i.e., computer, smartphone, internet access)
• Participants must be able to speak, understand and read English.
• Participants must have at least 20/40 visual acuity (correct or uncorrected).

Exclusion Criteria

• Current use of medications that interact adversely with yohimbine

  a. Iobenguane radiopharmaceutical products

• Current use of medications that interact adversely with hydrocortisone

  1. Aldesleukin
  2. Bacillus Calmette-Guérin (BCG) Products
  3. Cladribine
  4. Dengue Tetravalent Vaccine
  5. Desmopressin
  6. Indium 111 Capromab Pendetide
  7. Macimorelin
  8. Mifamurtide
  9. MiFEPRIStone
  10. Natalizumab
  11. Pimecrolimus:
  12. Ruxolitinib (Topical)
  13. Tacrolimus (Topical)
  14. Talimogene Laherparepvec
  15. Tertomotide
  16. Phenytoin
  17. Rifampin
  18. Troleandomycin
  19. Ketoconazole
  20. High-dose aspirin (>30 mg/kg/day)

• Contraindicated medical conditions of yohimbine

  1. Renal dysfunction
  2. Hepatic dysfunction
  3. Heart failure
  4. Psychotic Disorder or psychosis
  5. Hypotension
  6. Diabetes
  7. Heart disease
  8. Kidney disease
  9. Liver disease
  10. Nervous disorder
  11. Gastric ulcer
  12. Duodenal ulcer

• Contraindicated medical conditions of hydrocortisone

  1. Hypersensitivity to hydrocortisone or any component of the formulation
  2. Systemic fungal infections
  3. Latent Tuberculosis, Tuberculosis reactivity, active Tuberculosis
  4. Cardiovascular disease
  5. Diabetes
  6. Gastrointestinal diseases

  i. Diverticulitis ii. Fresh intestinal anastomoses iii. Active or latent peptic ulcer iv. Ulcerative colitis v. Abscess vi. Renal insufficiency vii. Other pyogenic infection g. Hepatic impairment h. Kidney impairment i. Myasthenia gravis j. Osteoporosis k. Pheochromocytoma l. Seizure disorders m. Septic shock or sepsis syndrome n. Systemic sclerosis o. Thyroid disease p. Strongyloides (threadworm) infestation q. Ocular herpes simplex r. Hypertension

• Given a live vaccine within 2 weeks of completing Visit 1. Recent administration of the following vaccines are specifically contraindicated for hydrocortisone:

  1. Typhoid Vaccine
  2. Yellow Fever Vaccine
  3. Poliovirus Vaccine (Live/Trivalent/Oral)
  4. Rubella- or Varicella-Containing Live Vaccines

• Have a current infection

• Pregnancy

• Individuals lactating

• Recent antihypertensive agents

• History of psychotic disorder, Bipolar I disorder, autism spectrum disorder, reactive attachment disorder, pervasive developmental disorder, motor disorder, head injury, mental retardation, neurological disorder, or current substance dependence

• Family history of Bipolar I disorder in a first degree relative.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hydrocortisone + Yohimbine	Yohimbine	Participants will ingest hydrocortisone and yohimbine during Session 2 approximately 10 minutes into the session.
Placebo + Placebo	Placebo	Participants will orally ingest two placebos during Session 2 approximately 10 minutes into the session.
Hydrocortisone + Yohimbine	Hydrocortisone	Participants will ingest hydrocortisone and yohimbine during Session 2 approximately 10 minutes into the session.

Primary Outcome Measures

Name	Time	Method
Goal-directed decision-making in the Social Decision Tree Task (SDTT)	Collected for 30 minutes ~1 hour into Session 2, which takes place on approximately Day 7 of the study	Measured by choice behavior in SDTT, which is based on the decision tree framework. After each action, participants receive feedback about the effect of that action and the extent to which it added to or took away from their points. If participants make a given choice, the subsequent actions that they can choose are different than if they were to initially make a different choice.; An action in SDTT is goal-directed if the possible net gain an individual can earn before the end of the current epoch (a "day" in the SDTT) is equal to or higher than the amount they could gain by choosing the alternative action. The investigators will subset trials so that 1 is coded as choosing the immediately valuable action at the expense of the optimal and 0 is coded as choosing the optimal at the expense of the immediately valuable action. This outcome variable is binary. An action is defined as social if it is paired with a visual cue with a face on it and non-social if not.
Pupil diameter during SDTT	Collected for 30 minutes ~1 hour into Session 2, which takes place on approximately Day 7 of the study	The outcome will be measured using eye tracking technology.
Change in salivary cortisol	Collected immediately before the drug/placebo administration (~5 minutes into the session) and 45 minutes after the drug/placebo administration (~50 minutes into the session) in Session 2, which takes place on approximately Day 7	The investigators will collect a saliva sample immediately before participants ingest the drugs (or placebos, if in the control condition). They will collect a second saliva sample 45 minutes after the drug (or placebo) ingestion. They will measure cortisol levels in both samples through an assay. The investigators will calculate the change in salivary cortisol by subtracting the measured cortisol in the first saliva sample (collected pre-drug/placebo ingestion) from the measured cortisol in the second saliva sample (collected 45 minutes after the drug/placebo ingestion). Salivary cortisol is measured as nmol/L. Salivary cortisol expected to generally be below 200 nmol/L.

Secondary Outcome Measures

Name	Time	Method
Change in valence, measured via the affect grid	Collected immediately before the first saliva collection in Session 2 (~5 minutes into the session) and 45 minutes after the second saliva collection in Session 2 (~50 minutes into the session), which takes place on approximately Day 7	Change in valence will be assessed through the affect grid. Participants will be presented with a 9x9 grid. The vertical dimension of the grid represents arousal, while horizontal dimension of the grid represents valence. The left side of the grid represents negative valence and the right side represents positive valence. Participants will click a square on the grid with their computer mouse to indicate their current affect. Their valence will be measured before the drug/placebo ingestion and 45 minutes after the drug/placebo administration. The minimum valence score is -4, representing extreme negative valence, and the maximum valence score is 4, representing extreme positive valence. The largest change in valence value is 8 (the maximum positive change in valence from time point 1 to time point 2). The smallest change in valence value is -8 (the maximum negative change in valence from time point 1 to time point 2). If no change in valence, the score will be 0.
Change in stress, measured via the subjective stress scale	Collected immediately before the first saliva collection in Session 2 (~5 minutes into the session) and 45 minutes after the second saliva collection in Session 2 (~50 minutes into the session), which takes place on approximately Day 7	Will be assessed via self-report using the one-item subjective stress scale. The scale ranges from 0 to 10. High values indicate more stress, whereas low values indicate less stress.
Change in arousal, measured via the affect grid	Collected immediately before the first saliva collection in Session 2 (~5 minutes into the session) and 45 minutes after the second saliva collection in Session 2 (~50 minutes into the session), which takes place on approximately Day 7	Change in arousal will be assessed through the affect grid. Participants will be presented with a 9x9 grid. The vertical dimension of the grid represents arousal, while horizontal dimension of the grid represents valence. The top of the grid represents high arousal and the bottom represents low arousal. Participants will click a square on the grid with their computer mouse to indicate their current affect. Their arousal will be measured before the drug/placebo ingestion and 45 minutes after the drug/placebo administration. The minimum arousal score is -4, representing extremely low arousal, and the maximum arousal score is 4, representing extremely high arousal. The largest change in arousal value is 8 (the maximum positive change in arousal from time point 1 to time point 2). The smallest change in arousal value is -8 (the maximum negative change in arousal from time point 1 to time point 2). If no change in arousal, the score would be 0.

Trial Locations

Locations (1)

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States