Investigating the Protective Impact of LY-2940094 on Stress-induced Depression- and Anxiety-related Phenotypes in Humans

Mass General Brigham

Status and phase: Withdrawn; Phase 2

Conditions: Anxiety; Stress; Depression - Major Depressive Disorder

Treatments: Drug: Nociceptin Receptor Antagonist (LY-2940094); Device: DS8R Biphasic Constant Current Stimulator

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06786637

5P50MH119467-05 (U.S. NIH Grant/Contract)

2023A062574

Details and patient eligibility

About

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.

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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0 participants in 2 patient groups, including a placebo group

Participants receiving the nociceptin receptor antagonist

Experimental group

Description:

After a diagnostic interview during the first visit, participants will receive the nociceptin receptor antagonist (LY-2940094) at the beginning of the second visit. Participants will then complete two computerized tasks (the Probabilistic Rewards Task (PRT) and a context fear conditioning paradigm). Tasks will begin 2 hours after the nociceptin receptor antagonist is administered.

Treatment:

Device: DS8R Biphasic Constant Current Stimulator

Drug: Nociceptin Receptor Antagonist (LY-2940094)

Participants receiving the placebo

Placebo Comparator group

Description:

After a diagnostic interview during the first visit, participants will receive the placebo at the beginning of the second visit. Participants will then complete two computerized tasks (the Probabilistic Rewards Task (PRT) and a context fear conditioning paradigm). Tasks will begin 2 hours after the placebo is administered.

Treatment:

Device: DS8R Biphasic Constant Current Stimulator