Trial of the Rapid Antisuicidal Effects of Intranasal Ketamine in Comorbid Depression and Alcohol Abuse

Sponsor

The University of Texas Health Science Center, Houston (Other)

Overall Status

Recruiting

CT.gov ID

NCT03539887

Collaborator

(none)

Enrollment

Location

Arms

55.8

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This project aims to evaluate the potential rapid and sustained antisuicidal and antidepressant effects of a single intranasal dose of ketamine in inpatients during a mood episode in Major Depressive Disorder (MDD) or Bipolar Disorder (BD) with or without comorbid recent abuse of alcohol.

Condition or Disease	Intervention/Treatment	Phase
Suicidal Ideation Depression Alcohol Abuse	Drug: Intranasal ketamine Drug: Placebo	Phase 3

Detailed Description

Clinicians have a limited ability to predict imminent suicidal behavior and efficacious treatments are not available to treat suicidal patients. Thus, Rapid-acting treatments for suicidal individuals are truly needed. This project aims to evaluate the potential rapid and sustained antisuicidal and antidepressant effects of a single intranasal dose of ketamine in inpatients during a mood episode (in Major Depressive Disorder, MDD or Bipolar Disorder, BD) with or without comorbid recent abuse of alcohol. These results will elucidate the antisuicidal effects of ketamine using the intranasal route along with the identification of associated mediators or moderators; this approach has the potential for enormous public health impact.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, Double-Blind, Placebo-ControlledRandomized, Double-Blind, Placebo-Controlled

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled Trial of the Rapid Antisuicidal Effects of Intranasal Ketamine in Comorbid Depression and Alcohol Abuse

Actual Study Start Date :

May 1, 2018

Anticipated Primary Completion Date :

Oct 30, 2022

Anticipated Study Completion Date :

Dec 25, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intranasal ketamine Intranasal ketamine	Drug: Intranasal ketamine Intranasal ketamine will be prepared as 100mg/ml ketamine in 0.9% saline. An mucosal atomization device will be used to provide 5 intranasal applications of solution (volume 100 μl), separated by 3 minutes, over a total of 15 minutes. Each of five ketamine applications will provide 10 mg of study drug, for a total of 50mg. The dose to be used (0.5-1mg/Kg) is 6 to 18 times lower than the sedation dose (6-9mg/Kg).
Experimental: Intranasal ketamine in alcohol abuse Intranasal ketamine	Drug: Intranasal ketamine Intranasal ketamine will be prepared as 100mg/ml ketamine in 0.9% saline. An mucosal atomization device will be used to provide 5 intranasal applications of solution (volume 100 μl), separated by 3 minutes, over a total of 15 minutes. Each of five ketamine applications will provide 10 mg of study drug, for a total of 50mg. The dose to be used (0.5-1mg/Kg) is 6 to 18 times lower than the sedation dose (6-9mg/Kg).
Placebo Comparator: Placebo non-active placebo	Drug: Placebo Saline alone. An mucosal atomization device will be used to provide 5 intranasal applications of saline (volume 100 μl), separated by 3 minutes, over a total of 15 minutes.
Placebo Comparator: Placebo in alcohol abuse non-active placebo	Drug: Placebo Saline alone. An mucosal atomization device will be used to provide 5 intranasal applications of saline (volume 100 μl), separated by 3 minutes, over a total of 15 minutes.

Outcome Measures

Primary Outcome Measures

Suicidal ideation as assessed by the Scale for Suicide Ideation (SSI) [24 hours]
The scale contains 19 items rated on a scale from 0 to 2, allowing score range from 0 to 38, score over 4 (first five items) will be considered inclusion criteria. Higher values indicate worsening or presence of suicidal ideation.

Secondary Outcome Measures

Depression as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS) [24 hours]
It has ten items, each item yields a score of 0 to 6. Hence the overall score ranges from 0 to 60. Higher scores indicate more severe depression.
Snaith-Hamilton Pleasure Scale [4 and 24 hours]
The Snaith-Hamilton Pleasure Scale (SHAPS) is an assessment of anhedonia, which has been extensively used by our group. The 14-item measure takes 5 minutes to complete (Snaith et al 1995).
Alcohol Urge Questionnaire (AUQ) [4 and 24hs]
Alcohol Urge Questionnaire (AUQ) is a multi-item measure of self- reported urges to drink alcohol, predictor of drinking abuse and relapse (Bohn MJ, Krahn DD, Staehler BA 1995) and AUDIT/CIWA.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Voluntary admission to Harris County Psychiatry Center
Able to provide written informed consent
Current suicidal ideation and depressive symptoms and Diagnostic and Statistical Manual of Mental Disorders -IV- Text Revision(DSM-IV-TR) depressive episode (also MADRS greater than or equal to 12) and Young Mania Rating Scale (YMRS) score lower than 8
DSM-IV-TR criteria for current alcohol abuse (but not intoxicated/withdrawal, abstinent from drinking for > 5 days prior to admission).
Lifetime history of suicide attempt (patient)
Not taking any medication in the last 24hs.
SSI score over 4 (first five items) and Columbia scale (C-SSRS) score 4 or 5

Exclusion Criteria:

Unstable medical condition or medical problem with known central nervous system (CNS) effects, e.g. uncontrolled hypertension systolic blood pressure (SBP) ≥170 and/or diastolic blood pressure (DBP) ≥100) or recent history (6 months) of alcohol-withdrawal seizures or significant abnormal laboratory tests (liver function test (LFT) 3 times higher than normal).
Prior diagnosis of a DSM-IV-TR psychotic spectrum disorder, psychotic symptoms, or personality disorder.
Currently under the acute effects of an illicit substance.
Pregnant or nursing women.
Subjects with a history of DSM-IV drug dependency or abuse (except for caffeine or nicotine dependence) within the preceding 3 months