Clinical trial NCT06018727: Role Of Sensitivity to neuroEndocrine Systems in Social Decisions
Official title: Role Of Sensitivity to neuroEndocrine Systems in Social Decisions
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Borderline Personality Disorder
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2023-08-31
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Goal-directed decision-making in the Social Decision Tree Task (SDTT)
timeFrame: Collected for 30 minutes ~1 hour into Session 2, which takes place on approximately Day 7 of the study
measure: Change in salivary cortisol
timeFrame: 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
measure: Pupil diameter during SDTT
timeFrame: Collected for 30 minutes ~1 hour into Session 2, which takes place on approximately Day 7 of the study
Secondary outcomes:
measure: Change in valence, measured via the affect grid
timeFrame: 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
measure: Change in arousal, measured via the affect grid
timeFrame: 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
measure: Change in stress, measured via the subjective stress scale
timeFrame: 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
Other outcomes:
measure: Personality Assessment Inventory-Borderline Scale (PAI-BOR) score
timeFrame: Session 1, which takes place on Day 0
measure: Interbeat Interval (IBI) time series during SDTT
timeFrame: Collected approximately 1 hour into Session 2 for 30 minutes (which takes place on approximately Day 7)
measure: Heart rate variability (HRV) during SDTT
timeFrame: Collected approximately 1 hour into Session 2 for 30 minutes (which takes place on approximately Day 7)
measure: Electrodermal activity (EDA) during SDTT
timeFrame: Collected approximately 1 hour into Session 2 for 30 minutes (which takes place on approximately Day 7)
measure: Skin conductance response during SDTT
timeFrame: Collected approximately 1 hour into Session 2 for 30 minutes (which takes place on approximately Day 7)
measure: World Health Organization Disability Assessment Schedule 2.0 (WHODAS) score
timeFrame: Session 1, which takes place on Day 0
measure: Working memory, assessed by the digit span score
timeFrame: Session 1, which takes place on Day 0
measure: Big Five Inventory (BFI-II) Score
timeFrame: Collected for 45 minutes after the drug/placebo administration in Session 2 (beginning ~10 minutes into the session), which takes place on approximately Day 7
measure: Inventory of Interpersonal Problems (IIP-90) Score
timeFrame: Collected for 45 minutes after the drug/placebo administration in Session 2 (beginning ~10 minutes into the session), which takes place on approximately Day 7
measure: Traumatic Life Events Questionnaire (TLEQ) Score
timeFrame: Collected for 45 minutes after the drug/placebo administration in Session 2 (beginning ~10 minutes into the session), which takes place on approximately Day 7
measure: Urgency, Premeditation (lack of), Perseverance (lack of), Sensation Seeking, Positive Urgency, Impulsive Behavior (UPPS-P) Score
timeFrame: Collected for 45 minutes after the drug/placebo administration in Session 2 (beginning ~10 minutes into the session), which takes place on approximately Day 7
measure: Drug Use Disorders Identification Test (DUDIT) Score
timeFrame: Collected for 45 minutes after the drug/placebo administration in Session 2 (beginning ~10 minutes into the session), which takes place on approximately Day 7
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) Severity of Substance Use (Past 3 months) - Calibrated Items
timeFrame: Collected for 45 minutes after the drug/placebo administration in Session 2 (beginning ~10 minutes into the session), which takes place on approximately Day 7
measure: Alcohol Use Disorders Identification Test (AUDIT) Score
timeFrame: Collected for 45 minutes after the drug/placebo administration in Session 2 (beginning ~10 minutes into the session), which takes place on approximately Day 7
measure: Personality Inventory for DSM-5 Faceted Brief Form (PID-5-FBF) Score
timeFrame: Collected for 45 minutes after the drug/placebo administration in Session 2 (beginning ~10 minutes into the session), which takes place on approximately Day 7
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Michael N Hallquist, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huys QJ, Eshel N, O'Nions E, Sheridan L, Dayan P, Roiser JP. Bonsai trees in your head: how the pavlovian system sculpts goal-directed choices by pruning decision trees. PLoS Comput Biol. 2012;8(3):e1002410. doi: 10.1371/journal.pcbi.1002410. Epub 2012 Mar 8.