Ketamine in Borderline Personality Disorder

NCT03395314 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 2000021457
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to test the potential of the rapid-acting anti-depressant ketamine to decrease suicidality in Borderline Personality Disorder (BPD). The rate of completed suicide in BPD is similar to that of depression or schizophrenia. There is currently no specific medication treatment for BPD. Ketamine is an FDA-approved anesthetic agent that has been shown to rapidly decrease suicidality and improve mood in people with Major Depressive Disorder (MDD). Though symptoms overlap, effective treatments for MDD and BPD differ. This clinical trial tests if ketamine also decreases suicidality and improves mood in BPD. This trial will also measure several other outcomes after ketamine versus placebo in BPD: adverse events, BPD symptoms, pain, social cognition, and neuroplasticity.

Conditions

Borderline Personality Disorder

Keywords

Borderline Personality Disorder; Ketamine; Suicide; Social Cognition

Outcome Measures

Primary Outcomes (4)

• Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS)

  The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. Scores are averaged across items and can range from 0 to 6 (with 0 indicating enjoying life, and 6 indicating explicit plans for suicide). Outcome description updated when results were entered.

  Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

• Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS)

  Suicide Rating Scale from 1-5; higher numbers indicate increased suicidal thinking.

  Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

• Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16)

  The Quick Inventory of Depressive Symptomatology (QIDS SR-16) is a a self-report measure of depression. Each item is scored from 0-3. Higher scores denote more severe load of depressive symptoms. Item 12 measures thoughts of death or suicide from 0 (no thoughts) to 3 (specific suicide plan or action.). Presented is the mean score across items with a range of 0 to 3 where the higher score indicates greater depressive symptoms. Outcome description was updated at the time of results entry.

  Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

• Change in Suicidality as Measured by Item 9 on Beck Depression Inventory

  When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is used to quantify the participant's degree of depression from 0 = no depression to 63 = maximally severe depression. Item 9 measures degree of suicidal thoughts or wishes from 0 = no thoughts to 3 = suicidal intent.

  Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

Secondary Outcomes (14)

• Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

  Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

• Change in Beck Depression Inventory Score

  Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

• Change in Beck Anxiety Inventory Score

  Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

• Change in Zanarini Rating Scale for Borderline Personality Disorder

  Timepoints will be baseline and at 1, 3, 7, 14, & 28 days after infusion.

• Change in Preferred Distance in Stop-distance Paradigm (SDP)

  Timepoints will be at baseline and 3, 7, 14, 28 days after infusion

Other Outcomes (3)

• Change in Bias Scores on the Implicit Association Tests (IAT) of Death, Escape and Self Harm Imagery.

  Timepoints: at baseline and 1, 3, 7, 28 days after infusion.

• Change in Resting State Electroencephalography (EEG)

  Timepoints: at baseline and 1 and/or 7 days after infusion.

• Change in Electroencephalography (EEG) Signal During Behavioral Neuroplasticity Task

  Timepoints: at baseline and 1 and/or 7 days after infusion.

Study Arms (2)

midazolam

PLACEBO COMPARATOR

Midazolam IV; 0.04mg/kg over 40 minutes

Drug: Midazolam

low dose ketamine

ACTIVE COMPARATOR

ketamine IV; 0.5 mg/kg over 40 minutes

Drug: Ketamine

Interventions

Ketamine DRUG

1 single dose of IV ketamine

low dose ketamine

Midazolam DRUG

1 single dose of IV midazolam

midazolam

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 21-60
• Clinical diagnosis of Borderline Personality Disorder
• Has suicidal ideation.
• Fluent in English
• Has a current mental health treater, and agrees for study to communicate with treater

You may not qualify if:

• Current suicidal intent
• Med changes in last 4 weeks
• Any ketamine in any context in the last one year.
• Current prescription for topiramate, lamotrigine, or lithium.
• Psychotic disorder in self or first-degree relative
• Current substance dependence including alcohol dependence
• Any history of NMDA (N-methyl-D-aspartate )-antagonist abuse
• Any history of opiate abuse
• History of major medical illness especially neurologic or cardiovascular condition, or any other medical contra-indication to ketamine administration at the discretion of the study MD.
• Positive urine test for drugs of abuse screening on day of ketamine administration
• Positive pregnancy test on day of ketamine administration
• At the discretion of study staff

Sponsors & Collaborators

• Yale University: lead
• Nathan Kline Institute for Psychiatric Research: collaborator
• American Foundation for Suicide Prevention: collaborator

Study Sites (2)

Connecticut Mental Health Center

New Haven, Connecticut, 06519, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Conditions

Borderline Personality Disorder; Suicide

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Personality Disorders; Mental Disorders; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Sarah Fineberg, MD, PhD
• Organization: Yale School of Medicine

sarah.fineberg@yale.edu

(203) 974-7265

Study Officials

• Sarah Fineberg, MD/PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2017
• First Posted: January 10, 2018
• Study Start: February 15, 2018
• Primary Completion: May 6, 2022
• Study Completion: May 6, 2022
• Last Updated: June 26, 2023
• Results First Posted: June 26, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)