NCT02543983

Brief 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. 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
325

participants targeted

Target at P75+ for phase_2 healthy-volunteers

Timeline
51mo left

Started Dec 2015

Longer than P75 for phase_2 healthy-volunteers

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress71%
Dec 2015Jul 2030

First Submitted

Initial submission to the registry

September 5, 2015

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 9, 2015

Completed
3 months until next milestone

Study Start

First participant enrolled

December 1, 2015

Completed
14.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 21, 2030

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 21, 2030

Last Updated

March 27, 2026

Status Verified

March 25, 2026

Enrollment Period

14.6 years

First QC Date

September 5, 2015

Last Update Submit

March 26, 2026

Conditions

Keywords

NeurobiologySuicideKetamineMajor Depressive DisorderBiomarkers

Outcome Measures

Primary Outcomes (5)

  • 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

    multiple time-points

  • Phase II: Scale for Suicide Ideation

    Clinical rating scale of suicidal ideation

    multiple time-points

  • Phase II: Montgomery-Asberg Depression Rating Scale

    Clinical rating scale of depression

    multiple time-points

  • Phase II: Hamilton Psychiatric Rating Scale for Anxiety

    Clinical rating scale of depression

    multiple time-points

  • Phase II: Clinical Global Impression Scale

    Clinical rating scale of psychiatric symptomology

    multiple time-points

Secondary Outcomes (2)

  • Anhedonia and Hopelessness via the Snaith-Hamilton Pleasure Scale & the Beck Hopelessness Scale

    multiple time-points

  • Baseline and Response Biomarkers

    multiple time-points

Study Arms (1)

1

EXPERIMENTAL

Ketamine Hydrochloride infusion

Device: Magnetic Resonance Imaging scanner, 3TDevice: NeurOptics PLRTM-3000 PupillometerDevice: Experimental Anxiety DevicesDevice: Magnetic Resonance Imaging scanner, 7TDrug: Ketamine Hydrochloride

Interventions

Non-significant risk device used for brain imaging.

1

The NeurOptics PLRTM-3000 Pupillometer will use quantitative infrared technology to objectively and accurately measure pupil size and dynamics.

1

Acoustic startle and shock devices are used to evaluate anxious responses to stimuli. Both are considered non-significant risk under this study.

1

Non-significant risk device used for brain imaging.

1

A non-competitive N-methyl-D-aspartate receptor antagonist. This drug is exempt from FDA IND review under the study.

1

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Phase I: Groups 1-3 and 5 (Patients)
  • 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)
  • 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
  • +4 more criteria

You may not qualify if:

  • 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.
  • 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.
  • +30 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (4)

  • Hu 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.

  • Lee 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.

  • Lamontagne 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.

  • Ballard 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.

Related Links

MeSH Terms

Conditions

DepressionSuicideDepressive Disorder, Major

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Behavioral SymptomsBehaviorSelf-Injurious BehaviorDepressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Study Officials

  • Carlos A Zarate, M.D.

    National Institute of Mental Health (NIMH)

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura R Waldman, L.C.S.W.

CONTACT

Carlos A Zarate, M.D.

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 5, 2015

First Posted

September 9, 2015

Study Start

December 1, 2015

Primary Completion (Estimated)

July 21, 2030

Study Completion (Estimated)

July 21, 2030

Last Updated

March 27, 2026

Record last verified: 2026-03-25

Data Sharing

IPD Sharing
Will share

Clinical and demographic and biomarker participant data collected during the trial, after deidentification.

Shared Documents
SAP
Time Frame
Starting within 1 year of completion of the study.
Access Criteria
The Branch Chief will review requests and access will need to be approved by the NIMH/DIRP SD and OCD NIMH and the NIH IRB.

Locations