Overview

Elucidating the Neurocircuitry of Irritability With High-Field Neuroimaging to Identify Novel Therapeutic Targets

Status:
Not yet recruiting
Trial end date:
2026-11-01
Target enrollment:
0
Participant gender:
All
Summary
The study is investigating dysfunctions in neurocircuitry in regards to irritability with healthy controls (HC) and individuals with Major Depressive Disorder (MDD) by performing MRIs. The MDD group will also be randomized to receive ketamine or midazolam to investigate changes post-treatment in neurocircuitry with regards to irritability.
Phase:
Phase 2
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
University of Texas Southwestern Medical Center
Treatments:
Ketamine
Midazolam
Criteria
Inclusion Criteria:

1. Male or female subjects, 18-65 years of age and body weight less than or equal to 120
kg on baseline visit.

2. Participants must have a level of understanding of the English language sufficient to
agree to all tests and examinations required by the study and must be able to
participate fully in the informed consent process.

3. For Healthy Controls: Subjects must be free of any lifetime psychiatric condition
based on the Mini-International Neuropsychiatric Interview (MINI). For MDD: Subjects
must meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for
current unipolar depression [major depressive disorder (MDD) or persistent depressive
disorder (PDD) in a current major depressive episode (MDE)] based on MINI.

4. A woman of childbearing potential who is sexually active with a male must agree to use
an acceptable method of contraception [defined as either one highly effective
(permanent sterilization, intrauterine device or hormonal implant) or two other forms
of contraception (such as oral contraceptive pill and condom)] to avoid pregnancy
throughout the study. Throughout the study and for 90 days (one spermatogenesis cycle)
after receiving the last dose of study drug (ketamine/midazolam) man who is sexually
active with a woman of childbearing potential must use an acceptable method of
contraception (described above) with his female partner and must agree not to donate
sperm.

5. Subjects must either be free of psychotropic medications (including antidepressants,
antipsychotics, benzodiazepines, mood stabilizers, sedative/hypnotics, dopamine
agonists, stimulants, buspirone, and triptans) and certain anticonvulsants (topiramate
and levetiracetam) or be stable on these medications for four weeks prior to the
baseline visit [first magnetic resonance imaging (MRI) scan].

6. Subjects with MDD should be willing to participate in neuroimaging scans before and
after infusions, and be willing to undergo infusions with study drug.

Exclusion Criteria:

1. Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder,
pervasive developmental disorder or intellectual development disorder.

2. Current diagnosis of obsessive-compulsive disorder, anorexia nervosa or bulimia.
Comorbid anxiety, stress and trauma-related disorders are permitted as long as
unipolar depression is the primary diagnosis.

3. Diagnosis of a moderate or severe substance use disorder within the past 6 months per
MINI; all subjects must have a negative urine toxicology test on the day of the MRI,
prior to the scan.

4. Female subjects who are pregnant, nursing, for may become pregnant. Women of
childbearing potential must have a negative urine pregnancy test on the day of the
fMRI, prior to scan, and on days of study drug infusion, prior to infusion.

5. Any unstable medical illnesses including hepatic, renal, gastroenterologic,
respiratory, cardiovascular (including ischemic heart disease), endocrinologic,
immunologic, or hematologic disease.

6. Inadequately treated obstructive sleep apnea (STOP-Bang score of 5-8 if untreated, if
using positive airway pressure device then past-month apnea hypopnea index ≥ 15 per
hour representing moderate or higher severity).

7. Presence of a significant neurological disease such as Parkinson's disease, primary or
secondary seizure disorders, intracranial tumors, or severe head trauma.

8. Presence of neurocognitive or dementing disorders.

9. Clinically significant abnormalities of laboratories, physical examination (including
unstable hypertension - systolic blood pressure >170, diastolic blood pressure >100),
or electrocardiogram at screening visit.

10. Subjects judged to be at serious and imminent suicidal or homicidal risk by the PI or
another study-affiliated psychiatrist.

11. Any contraindications to MRI, including pacemakers or metallic objects in the body.

12. Any claustrophobia or other conditions which may result in inability to lie still in
the MRI scanner for 1 hour or more.

13. Allergy to ketamine or midazolam in subjects with MDD.

14. Must not be on any prohibited concomitant medication.