Neurobiology of Suicide
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02543983 |
Recruitment Status :
Recruiting
First Posted : September 9, 2015
Last Update Posted : April 25, 2024
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Healthy Volunteers Depression | Device: Magnetic Resonance Imaging scanner, 3T Device: NeurOptics PLRTM-3000 Pupillometer Device: Experimental Anxiety Devices Device: Magnetic Resonance Imaging scanner, 7T Drug: Ketamine Hydrochloride | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 325 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Basic Science |
Official Title: | The Neurobiology of Suicide |
Actual Study Start Date : | December 1, 2015 |
Estimated Primary Completion Date : | July 21, 2025 |
Estimated Study Completion Date : | July 21, 2025 |
Arm | Intervention/treatment |
---|---|
Experimental: 1
Ketamine Hydrochloride infusion
|
Device: Magnetic Resonance Imaging scanner, 3T
Non-significant risk device used for brain imaging. Device: NeurOptics PLRTM-3000 Pupillometer The NeurOptics PLRTM-3000 Pupillometer will use quantitative infrared technology to objectively and accurately measure pupil size and dynamics. Device: Experimental Anxiety Devices Acoustic startle and shock devices are used to evaluate anxious responses to stimuli. Both are considered non-significant risk under this study. Device: Magnetic Resonance Imaging scanner, 7T Non-significant risk device used for brain imaging. Drug: Ketamine Hydrochloride A non-competitive N-methyl-D-aspartate receptor antagonist. This drug is exempt from FDA IND review under the study. |
- Study as Whole: Psychiatric, psychological, neuroimaging, sleep and biological differences between participants in Groups 1, 2, 3, 4, and 5 [ Time Frame: multiple time-points ]Clinical and research data and samples
- Phase II: Scale for Suicide Ideation [ Time Frame: multiple time-points ]Clinical rating scale of suicidal ideation
- Phase II: Montgomery-Asberg Depression Rating Scale [ Time Frame: multiple time-points ]Clinical rating scale of depression
- Phase II: Hamilton Psychiatric Rating Scale for Anxiety [ Time Frame: multiple time-points ]Clinical rating scale of depression
- Phase II: Clinical Global Impression Scale [ Time Frame: multiple time-points ]Clinical rating scale of psychiatric symptomology
- Anhedonia and Hopelessness via the Snaith-Hamilton Pleasure Scale & the Beck Hopelessness Scale [ Time Frame: multiple time-points ]Clinical rating scale of anhedonia and hopelessness
- Baseline and Response Biomarkers [ Time Frame: multiple time-points ]Biomarkers
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
- INCLUSION CRITERIA:
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 greater than or equal to 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)
- 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 greater than or equal to 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 (see Monitoring Suicide Risk section).
- 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.
EXCLUSION CRITERIA:
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.
- 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 (Omega) 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 (Omega) 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02543983
Contact: Laura R Waldman, L.C.S.W. | (301) 402-9348 | moodresearch@mail.nih.gov | |
Contact: Carlos A Zarate, M.D. | (877) 646-3644 | zaratec@mail.nih.gov |
United States, Maryland | |
National Institutes of Health Clinical Center | Recruiting |
Bethesda, Maryland, United States, 20892 |
Principal Investigator: | Carlos A Zarate, M.D. | National Institute of Mental Health (NIMH) |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | National Institute of Mental Health (NIMH) |
ClinicalTrials.gov Identifier: | NCT02543983 |
Other Study ID Numbers: |
150188 15-M-0188 |
First Posted: | September 9, 2015 Key Record Dates |
Last Update Posted: | April 25, 2024 |
Last Verified: | March 4, 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | .Clinical and demographic and biomarker participant data collected during the trial, after deidentification. |
Supporting Materials: |
Statistical Analysis Plan (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. |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | Yes |
Device Product Not Approved or Cleared by U.S. FDA: | Yes |
Neurobiology Suicide Ketamine Major Depressive Disorder Biomarkers |
Suicide Behavioral Symptoms Self-Injurious Behavior Ketamine Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anesthetics, Dissociative |
Anesthetics, Intravenous Anesthetics, General Anesthetics Central Nervous System Depressants Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action |