Ketamine in Borderline Personality Disorder

NCT ID: NCT03395314

Last Updated: 2023-06-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-15
• Study Completion Date: 2022-05-06

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.

Detailed Description

This clinical trial primarily tests the impact of ketamine on suicidal thoughts in Borderline Personality Disorder (BPD). It also tests the impact of ketamine on symptom intensity (for mood, BPD, and pain symptoms), social cognition, and neuroplasticity in people with BPD.

Suicidal ideation and action are too common in BPD, occurring at rates similar to those in people with depression or schizophrenia. Intensive psychotherapy helps, but many people with BPD do not have access to that treatment, and not everyone responds to psychotherapy if they do get access. No medication is FDA-approved for BPD, and no medication has been shown to decrease suicidality in BPD.

Ketamine is a promising medication for this problem. It is an FDA-approved anesthetic medication with N-methyl D-aspartate activity. Sub-anesthetic doses of ketamine decrease suicidality and improve mood in people with Major Depressive Disorder (MDD). This effect is rapid, with symptom improvement within hours that endures approximately two weeks. People with BPD can have symptoms that overlap with those of MDD, however, the effective treatments for BPD and MDD differ. This clinical trial will test if ketamine, which is effective in MDD, is also effective in BPD.

The investigators will use semi-structured interviews and self-report questionnaires to measure suicidal ideation and clinical symptoms (adverse events, mood symptoms, BPD symptoms, and pain). Social cognition will be also be measured using both interviews/questionnaires and cognitive psychology tasks.

One proposed mechanism of ketamine's effect in MDD is increased neuroplasticity - opening a window during which new learning can occur. This mechanism has been demonstrated in rodent models of depression. In BPD, negatively-biased social interpretations impede meaningful recovery and increase suicide risk over time. A post-ketamine neuro-plastic window may provide an opportunity for revisions of rigid social attributions. The investigators will test for changes in neuroplasticity using a cognitive psychology task and electro-encephalography.

Baseline measures of demographics, life experiences, and symptoms may also be used to predict outcomes or as co-variates in our analyses.

Conditions

Borderline Personality Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

midazolam

Midazolam IV; 0.04mg/kg over 40 minutes

Group Type: PLACEBO_COMPARATOR

Midazolam

Intervention Type: DRUG

1 single dose of IV midazolam

low dose ketamine

ketamine IV; 0.5 mg/kg over 40 minutes

Group Type: ACTIVE_COMPARATOR

Ketamine

Intervention Type: DRUG

1 single dose of IV ketamine

Interventions

Ketamine

1 single dose of IV ketamine

Intervention Type: DRUG

Midazolam

1 single dose of IV midazolam

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nathan Kline Institute for Psychiatric Research

OTHER

Sponsor Role: collaborator

American Foundation for Suicide Prevention

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sarah Fineberg, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Connecticut Mental Health Center

New Haven, Connecticut, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2000021457

Identifier Type: -

Identifier Source: org_study_id