Healthy VolunteersPhase 2NCT02543983
Neurobiology of Suicide
A Phase 2 study testing Magnetic Resonance Imaging scanner, 3T, NeurOptics PLRTM-3000 Pupillometer and Experimental Anxiety Devices in people with Healthy Volunteers and Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: There are no good treatments for people considering suicide. Researchers want to study suicide with questions, blood tests, brain imaging, and sleep studies. They hope to better understand suicide, so they can help suicidal people. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers, Depression
- What is being tested?
- Magnetic Resonance Imaging scanner, 3T, NeurOptics PLRTM-3000 Pupillometer and Experimental Anxiety Devices
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 325 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2015to 21 Jul 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Phase I: Groups 1-3 and 5 (Patients)
- 18 to 70 years of age.
- A level of understanding sufficient to agree to all required tests and examinations, sign an informed consent document and verify understanding by a score >= 90% on the Baseline consent quiz
- Individuals who are able to get pregnant must be willing to remain sexually abstinent or use at least one form of effective birth control during participation in Phase I.
- Additional Criteria for Group 1 (Active Crisis): Agree to be hospitalized
- Phase I: Group 4 (Healthy Volunteers)
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- 18 to 70 years of age.
- A level of understanding sufficient to agree to all required tests and examinations, sign an informed consent document.
- Individuals who are able to get pregnant must be willing to remain sexually abstinent or use at least one form of effective birth control during participation in Phase I.
- Phase II: Group 1 (Active Crisis) and Group 5 (Suicide Ideators)
- Patients must have completed Study Phase I as a participant in Group 1 or 5
- Participants must verify understanding of the protocol by a score >= 80% on the Ketamine Response consent quiz.
- Patients in Group 1 or 5 must report at least minimal suicidal ideation, depressive or anxiety symptoms to be eligible for this phase.
- MADRS score of over 10 (10 used as an outcome measure for remission)126
- OR HAMA score of over 7 (7 used as an outcome measure for remission)127
- OR SSI score of 2 or more (indicates any residual suicidal thoughts)
- Individuals who are able to get pregnant must be willing to remain sexually abstinent or use at least one form of effective birth control during participation in Phase II.
- Phase III: Group 1 (Active Crisis) and Group 5 (Suicide Ideators)
- Participants must have met all inclusion criteria for and completed Study Phase II as a participant in Group 1 (active crisis) or Group 5 (Suicide Ideators).
- Individuals who are able to get pregnant must be willing to remain sexually abstinent or use at least one form of effective birth control during participation in Phase III.
Who cannot join
- Phase I: Groups 1-3 and 5 (Patients)
- Current psychotic features or cognitive impairment that would preclude understanding of the consenting process or tests/examinations.
- Current drug or alcohol dependence
- Currently intoxicated or under the acute effects of an illicit substance will not be consented into the study.
- Pregnant or nursing individuals or those who plan to become pregnant.
- Serious, unstable medical conditions/problems including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including blood pressure, ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
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- Clinically significant abnormal laboratory tests.
- Positive HIV test
- Participants who, in the investigator s judgment, pose a current homicidal risk or pose suicide risk that cannot be managed in a secure, voluntary inpatient setting.
- Non-English speakers
- Additional Criteria for Group 1 (Active Crisis): For participants who still experience the effects of their suicide attempt, i.e. someone who overdosed is significantly drowsy or confused, the consenting process will occur after the patient has improved from the effects. If there is a concern around a participant's capacity to consent, the Human Subjects Protections Unit (HSPU) team member who is
- monitoring the informed consent process will complete a capacity assessment. Participants who are determined not to have capacity to consent to research will not be included in the study.
- Phase I: Group 4 (Healthy Volunteers)
- Current or past Axis I diagnosis
- Presence of medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications.
- Current or past alcohol or substance abuse or dependence diagnosis (except for nicotine or caffeine) (or "substance abuse disorder" per DSM-V).
- Presence of psychiatric disorders or a history of suicide attempt or death in first-degree relatives.
- Pregnant or nursing individuals or those who plan to become pregnant.
- No lifetime suicide attempts or ideations
- Non-English speakers
- Positive HIV test
- Exclusions for Imaging:
- Participants with metal objects implanted in the body, such as aneurysm clips, neural stimulators, implanted cardiac pacemakers, or auto-defibrillator, cochlear implant, or ocular foreign body which would make having an MRI scan unsafe
- Participants who are uncomfortable in small closed spaces (have claustrophobia) and would feel uncomfortable in the MRI machine
- Participants with a brain abnormality on an initial MRI scan
- Subjects with hearing loss that has been clinically evaluated and diagnosed and may be worsened through participation in imaging procedures
- Phase II: Group 1 (Active Crisis) and Group 5 (Suicide Ideators)
- Treatment with a reversible MAOI within 2 weeks prior to study Phase II.
- Treatment with any other concomitant medication not allowed within 5 1/2 half-lives prior to study Phase II.
- Subjects with one or more seizures without a clear and resolved etiology
- Participants with a positive urine for an illicit substance no more than 24 hours prior to the ketamine infusion.
- Presence of current psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder as defined in the DSM-IV or DSM-V
- Pregnant or nursing individuals or those who plan to become pregnant.
- A medical finding or condition that in the clinical judgement of the investigator increases the risk of adverse effects from the ketamine administration (for example: findings suggesting difficulties with kidney or cardiac function that may be contraindications for an experimental intervention).
- Phase III: Repeated Administration (Group 1) and Group 5 (Suicide Ideators)
- Intolerable or serious adverse reaction to ketamine during Phase II
- Treatment with a reversible MAOI within 2 weeks prior to study Phase III.
- Treatment with any other concomitant medication not allowed within 5 1/2 half-lives prior to study Phase III.
- Subjects with one or more seizures without a clear and resolved etiology
- Participants with a positive urine for an illicit substance no more than 24 hours prior to each ketamine infusion.
- Presence of current psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder as defined in the DSM-IV or DSM-V
- Pregnant or nursing individuals or those who plan to become pregnant.
- Exclusions for Imaging:
- Participants with metal objects implanted in the body, such as aneurysm clips, neural stimulators, implanted cardiac pacemakers, or auto-defibrillator, cochlear implant, or ocular foreign body which would make having an MRI scan unsafe
- Participants who are uncomfortable in small closed spaces (have claustrophobia) and would feel uncomfortable in the MRI machine
- Participants with a brain abnormality on an initial MRI scan
- Subjects with hearing loss that has been clinically evaluated and diagnosed and may be worsened through participation in imaging procedures
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Carlos Zarate, M.D., 877-646-3644, moodresearch@mail.nih.gov
About this study
Official title: The Neurobiology of Suicide
Background:
There are no good treatments for people considering suicide. Researchers want to study suicide with questions, blood tests, brain imaging, and sleep studies. They hope to better understand suicide, so they can help suicidal people.
Read more
Objective:
To understand what happens in the brain when someone has thought about or attempted suicide.
Eligibility:
Group 1: Adults ages 18 70 who have thought about or attempted suicide recently
Group 2: Adults ages 18 70 who have thought about or attempted suicide in the past
Group 3: Adults ages 18 70 who have depression or anxiety, but have never thought about suicide
Group 4: Healthy volunteers the same ages.
Design:
Participants will be screened in another protocol. Adults who have recently thought about or attempted suicide must be referred by a doctor. They may do up to 3 phases of this study. Groups 2, 3 and 4 will do only Phase 1 and will not get ketamine.
Phase 1: 1 week in hospital. Participants will have:
Physical exam.
Questions about thoughts and feelings.
Thinking and memory tests and simple tasks.
Blood and urine tests.
Two MRI scans. Participants will lie on a table that slides into a metal cylinder that takes pictures. They will have a coil over their head and earplugs and do a computer task.
Sleep test. Disks and bands will be placed on the body to monitor it during sleep.
Magnetic detectors on their head while they perform tasks.
A wrist monitor for activity and sleep.
Lumbar puncture (optional). A needle will collect fluid from the back.
Shock experiments (optional). Participants will observe pictures and sounds and feel a small shock on the hand.
Phase 2: 4 days in hospital. A thin plastic tube will be placed in each arm, one for blood draws, the other to get the drug ketamine once. Participants will repeat most of the Phase 1 tests.
Phase 3: up to 4 more ketamine doses over 2 weeks.
Participants will have follow-up calls or visits at 6 months and then maybe yearly for 5 years.
Read the detailed description
- Objective
Suicide occurs across demographics and psychiatric disorders, killing at least one million individuals worldwide each year. In contrast to other injury-related death such as homicide or motor vehicle accidents, suicide rates have increased, particularly among middle-aged adults. Clinicians have a limited ability to predict imminent suicidal behavior and few, if any, efficacious treatments are available to treat suicidal patients. Advances in the treatment of the suicidal patients have been hampered by an incomplete understanding of the neurobiological underpinnings of the suicidal crisis, as suicidal thoughts and behaviors have not been clearly linked with specific neural circuits.
The aim of this study is to evaluate possible biomarkers of suicidal thoughts and behaviors in individuals currently experiencing a suicidal crisis. In taking a dimensional approach to suicide research, we will be able to study phenomenology across Research Domain Criteria (RDoC) units of analysis, from genes through circuits to self-report and experimental paradigms. Through this approach, we can identify potential neurobiological risk factors for both short and long-term suicide risk. As a secondary aim, we will use ketamine to identify biomarkers of ketamine response in a sample at acute risk for suicide.
- Study Population
Five participant populations will be recruited into this protocol in order to encompass the continuum of suicide risk. A total of 325 individuals will be enrolled in the study. Participant populations are individuals with the following conditions: 1.) recent suicidal ideation with intent and/or suicide attempt (Group 1- "active crisis", n= 65); 2) a past history of suicide attempt, but no suicidal behavior in the last year (Group 2, n= 65, "attempters"); 3) anxiety or mood symptoms, but no recent or past suicidal thoughts or behavior (Group 3, n= 65); 4) healthy controls with no psychiatric or suicide history (Group 4, n= 65); and lifetime suicidal thoughts with intent (Group 5, n=65, ideators ).
- Design
The research protocol will occur across three phases: baseline, ketamine response and optional repeated infusions. All participants will first be consented into Phase I, which may last up to seven days. This baseline phase will entail multimodal assessment, using pathophysiological markers (blood draw, lumbar puncture), neuroimaging (fMRI, MEG), polysomnography, clinical ratings and experimental paradigms (shock experiments). Participants will receive their regularly scheduled daily medications, but will not receive additional treatment (including new prn medications, such as benzodiazepines for management of anxiety or agitation) during this brief baseline phase. After completion of Phase I, eligible participants from Group 1 or 5 only (active crisis or ideators) will be offered participation in Phase II, the ketamine response phase. This phase, which will last up to four days, consists of a single, open-label trial of ketamine (0.5 mg/kg). The focus of this phase will be identification of potential biomarkers of antisuicidal ketamine response. Participants who complete Phase II will be offered Phase III, which will involve repeated ketamine infusions over two weeks (2 times/ per week for 2 weeks). Psychiatric medication adjustment will be permitted during Phase III.
After participation in Phases I-III, participants in Groups 1-3 and 5 will be offered standard clinical treatment (excluding healthy controls), or participation in another protocol. In standard clinical treatment, adjustment of psychiatric medications and commencement of psychotherapeutic interventions will be permitted. Finally, participants in Groups 1-3 and 5 will receive follow-up evaluations at six months after completion of Study Phase I.
- Outcome Measures
In Phase I, the outcome measures will be underlying psychiatric, psychological, neuroimaging, sleep and biological differences between the participant groups. In Phase II, the outcome measures will be reductions in suicidal thoughts and depressive and anxiety symptoms at 24 hours post-ketamine infusion.
- Conditions
- Healthy Volunteers, Depression
- Being tested
- Magnetic Resonance Imaging scanner, 3T, NeurOptics PLRTM-3000 Pupillometer, Experimental Anxiety Devices, Magnetic Resonance Imaging scanner, 7T, Ketamine Hydrochloride
- Keywords
- Neurobiology, Suicide, Ketamine, Major Depressive Disorder, Biomarkers
- Medical subject headings
- Depression, Suicide, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance Imaging scanner, 3TDevice
Non-significant risk device used for brain imaging.
NeurOptics PLRTM-3000 PupillometerDevice
The NeurOptics PLRTM-3000 Pupillometer will use quantitative infrared technology to objectively and accurately measure pupil size and dynamics.
Experimental Anxiety DevicesDevice
Acoustic startle and shock devices are used to evaluate anxious responses to stimuli. Both are considered non-significant risk under this study.
Magnetic Resonance Imaging scanner, 7TDevice
Non-significant risk device used for brain imaging.
Ketamine HydrochlorideDrug
A non-competitive N-methyl-D-aspartate receptor antagonist. This drug is exempt from FDA IND review under the study.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Ketamine Hydrochloride infusion Receives: Device: Magnetic Resonance Imaging scanner, 3T; Device: NeurOptics PLRTM-3000 Pupillometer; Device: Experimental Anxiety Devices; Device: Magnetic Resonance Imaging scanner, 7T; Drug: Ketamine Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study as Whole: Psychiatric, psychological, neuroimaging, sleep and biological differences between participants in Groups 1, 2, 3, 4, and 5
Clinical and research data and samples
Measured: multiple time-points
Phase II: Scale for Suicide Ideation
Clinical rating scale of suicidal ideation
Measured: multiple time-points
Phase II: Montgomery-Asberg Depression Rating Scale
Clinical rating scale of depression
Measured: multiple time-points
Phase II: Hamilton Psychiatric Rating Scale for Anxiety
Clinical rating scale of depression
Measured: multiple time-points
Phase II: Clinical Global Impression Scale
Clinical rating scale of psychiatric symptomology
Measured: multiple time-points
Secondary outcomes (2)
Anhedonia and Hopelessness via the Snaith-Hamilton Pleasure Scale & the Beck Hopelessness Scale
Clinical rating scale of anhedonia and hopelessness
Measured: multiple time-points
Baseline and Response Biomarkers
Biomarkers
Measured: multiple time-points
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2015 (estimated)
- Study start1 Dec 2015
- Primary completion21 Jul 2030 (estimated)
- Study completion21 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 325 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Carlos A Zarate, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02543983
- Sponsor's protocol ID
- 150188
- Other IDs
- 15-M-0188
- Status last verified
- 4 Sep 2026
- First submitted
- 5 Sep 2015
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Clinical and demographic and biomarker participant data collected during the trial, after deidentification.
Publications
Ballard ED, Hafermann H, Hurst K, Farmer C, Greenstein D, Kvarta M, May AM, Zarate CA Jr. Treatments for Individuals with Suicidal Thoughts: Use, Indications, and Helpfulness. J Affect Disord Rep. 2026 Dec;26:101165. doi: 10.1016/j.jadr.2026.101165. Epub 2026 Sep 7.
PubMed 42808010Gorka A, Evans J, Kvarta M, Ballard E, Zarate C. Major depressive disorder is associated with reduced intrinsic connectivity between the bed nucleus of the stria terminalis and ventral striatum. J Psychiatry Neurosci. 2026 Jan 1;51:1-7. doi: 10.1139/jpn-2025-0160.
PubMed 42171126Hu H, Lee Y, Tillman AN, Ballard ED, Waldman L, Yuan P, Johnston JN, Peng S, Kvarta MD, Verbalis JG, Zarate CA Jr. Blunted arginine vasopressin secretion in individuals experiencing a major depressive episode with comorbid post-traumatic stress disorder: Results from an exploratory study using copeptin as a surrogate marker. J Neuroendocrinol. 2026 Jan;38(1):e70133. doi: 10.1111/jne.70133.
PubMed 41555748Lee Y, Gilbert JR, Waldman LR, Zarate CA Jr, Ballard ED. Potential association between suicide risk, aggression, impulsivity, and the somatosensory system. Soc Cogn Affect Neurosci. 2024 Jul 2;19(1):nsae041. doi: 10.1093/scan/nsae041.
PubMed 38874947Lamontagne SJ, Gilbert JR, Zabala PK, Waldman LR, Zarate CA Jr, Ballard ED. Clinical, behavioral, and electrophysiological profiles along a continuum of suicide risk: evidence from an implicit association task. Psychol Med. 2024 May;54(7):1431-1440. doi: 10.1017/S0033291723003331. Epub 2023 Nov 24.
PubMed 37997749Ballard ED, Park LT, Pao M, Zarate CA. Clinical Trials With Suicidal Individuals Can Be Conducted Safely. J Clin Psychiatry. 2020 Aug 4;81(5):20l13353. doi: 10.4088/JCP.20l13353. No abstract available.
PubMed 32757505