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

Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03539887
• Other study ID #: HSC-MS-17-0903
• Status: Completed
• Phase: Phase 3
• Start date: May 1, 2018
• Est. completion date: January 15, 2022

Study information

• Verified date: February 2023
• Source: The University of Texas Health Science Center, Houston
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: January 15, 2022
• Est. primary completion date: January 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 60 Years

Eligibility

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.

• Scale for Suicide Ideation (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

Related Conditions & MeSH terms

• Alcohol Abuse
• Alcoholism
• Depression
• Depressive Disorder
• Suicidal Ideation

Intervention

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
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.

Locations

Country	Name	City	State
United States	The University of Texas Health Science Center at Houston	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Suicidal Ideation as Assessed by the Scale for Suicide Ideation (SSI)	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.	24 hours
Secondary	Depression as Assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS)	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.	24 hours
Secondary	Snaith-Hamilton Pleasure Scale	The Snaith-Hamilton Pleasure Scale (SHAPS) is an assessment of anhedonia, which is the inability to experience pleasure. The SHAPS has 14 items. Each item has four possible responses: strongly disagree, disagree, agree, or strongly agree. A response of "strongly disagree" or "disagree" equals one point, and a response of "strongly agree" or "agree" equals 0 points. Thus, the final score ranges from 0 to 14. A score of 2 or less constitutes a "normal" score, while an "abnormal" score is defined as 3 or more.	24 hours
Secondary	Alcohol Urge Questionnaire (AUQ)	Alcohol Urge Questionnaire (AUQ) is a multi-item measure of self-reported urges to drink alcohol, predictor of drinking abuse and relapse. AUQ is an 8-item questionnaire.; Each item is scored on a 1 to 7 scale (Strongly Disagree = 1 and Strongly Agree = 7). Items 2 and 7 are reverse scored. Total score ranges from 8 to 56, and a higher score reflects greater craving.	24 hours
Secondary	Manic Symptoms as Assessed by Score on the Young Mania Rating Scale (YMRS)	The YMRS has 11 items, and total score ranges from 0 to 88, with a higher score indicating greater mania.	24 hours
Secondary	Dissociative State as Assessed by Score on Clinician-Administered Dissociative States Scale (CADSS)	The CADSS consists of 23 items, and each item is rated on a scale from 0 (not at all) to 4 (severe), with the total score ranging from 0 to 92. A higher score indicates greater severity of dissociative state.	24 hours

External Links

•   Department of Psychiatry, Dr Rodrigo Machado-Vieira
•   Experimental Therapeutics and Molecular Pathophysiology, UTHealth, Houston, Texas