Clinical trial NCT06786637: Investigating the Protective Impact of LY-2940094 on Stress-induced Depression- and Anxiety-related Phenotypes in Humans
Official title: A Combined Investigation of the Protective Impact of the NOF/Q Antagonist LY-2940094 on Stress-induced Depression- and Anxiety-related Phenotypes in Humans
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Depression - Major Depressive Disorder
Anxiety
Stress
Lead sponsor: Mclean Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2025-01-22
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This project will integrate pharmacological and psychophysiological methodology to mechanistically investigate, in humans, the role of N/OFQ in laboratory phenotypes of both disorders. Specifically, a N/OFQ receptor (NOPR) antagonist will be used to test the hypothesis that NOPR blockage will have antidepressant-like effects (potentiate reward processing); in addition, this study will also evaluate a key anxiety phenotype (fear learning). Finally, the impact of recent life stress on these processes will be assessed. Results will demonstrate the specificity of NOPR blockage on depressive phenotypes or suggest a common pathway for emotional disorders and will confirm a modulatory role of life stress.


Eligibility criteria: Inclusion Criteria:

* Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse), as assessed by subject history and a structured clinical interview (diagnosed using the SCID-5)
* Written informed consent
* Absence of any medications for at least 3 weeks

Exclusion Criteria:

* Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician
* Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception
* Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
* History of seizure disorder
* History or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, obsessive-compulsive disorder, patients with mood congruent or mood incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse; which will lead to exclusion)
* History of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine)
* History of use of dopaminergic drugs (including methylphenidate)
* History or current diagnosis of dementia
* Patients with mood congruent or mood incongruent psychotic features
* Current use of other psychotropic drugs
* Clinical or laboratory evidence of hypothyroidism
* Patients with a lifetime history of electroconvulsive therapy
* Abnormal ECG and lab results
* History of seizure disorder or currently on anticonvulsants

Primary outcomes:
measure: Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (SCID-5)
timeFrame: Baseline
measure: Childhood Trauma Questionnaire (CTQ)
timeFrame: Baseline
measure: List of Threatening Experiences Questionnaire (LTE)
timeFrame: Baseline
measure: Combined Cue-Context Fear Conditioning Task: Subjective Fear Ratings
timeFrame: Baseline
measure: Probabilistic Reward Task (PRT)
timeFrame: Baseline
measure: Perceived Stress Scale
timeFrame: Baseline
measure: Combined Cue-Context Fear Conditioning Task: Skin Conductance Responce (SCR)
timeFrame: Baseline
measure: Combined Cue-Context Fear Conditioning Task: Fear-Potentiated Startle (FPS)
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Mclean Hospital
name: Manuel Kuhn, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: