Effects of Ketamine in the Acute Phase of Suicidal Ideation

Suicidal Ideation Clinical Trial

— KETIS  

Official title:

Evaluation of the Effects of Ketamine in the Acute Phase of Suicidal Ideation: a Multicenter Randomized Double-blind Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02299440
• Other study ID #: PHRC-N/2013/MA-01
• Secondary ID: 2014-001324-30
• Status: Completed
• Phase: Phase 3
• Start date: April 2015
• Est. completion date: March 26, 2019

Study information

• Verified date: March 2019
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to assess the efficacy of ketamine versus a placebo for the short-term (at 72h, i.e. 24h after the last perfusion) relief of suicidal ideation, measured using the BSS hetero questionnaire, in patients hospitalized for suicide risk.

Description:

The secondary objectives of this study are to assess:

A. The maintenance of medium-term effectiveness of ketamine on the resolution of suicidal ideation

B. The evolution of the full spectrum of suicidality under ketamine compared to placebo

C. The evolution of psychic and physical pain scores under ketamine compared to placebo

D. The evolution of Beck Hopelessness score which is a predictor of long-term suicide risk, under ketamine compared to placebo

E. The early antidepressant efficacy of ketamine in depressed, uni- or bipolar patients

F. The somatic and psychological tolerance of ketamine

G. An overall improvement in the clinical condition of the patient by the practitioner

H. Creation of a biological collection for future ancillary studies dedicated to genetic analysis (microRNA and mRNA).

I. The efficacy of ketamine versus a placebo for the short-term (at 72h, i.e. 24h after the last perfusion) relief of suicidal ideation, measured using the BSS self-report questionnaire, in patients hospitalized for suicide risk.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: March 26, 2019
• Est. primary completion date: March 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• French speaking patients freely hospitalized for prevention of suicide and who have a medium or high suicide risk score according to a MINI structured interview

• The patient is able to understand how the study is carried out and the tests performed

• The patient is deemed capable of giving his/her informed consent

• The patient has been correctly informed

• The patient must have given his/her informed and signed consent.

• The patient must be insured or beneficiary of a health insurance plan.

• Presence of suicidal ideation according to the SSI score (score > 3)

• Negative pregnancy test for women of childbearing age

Exclusion Criteria:

• The patient is participating in another interventional study

• Within the past three months, the patient has participated in another interventional study

• The patient is in an exclusion period determined by a previous study

• The patient is under judicial protection

• The patient is an adult under guardianship

• The patient refuses to sign the consent

• The patient is not able to understand the informed consent

• Pregnancy or breastfeeding

• History of schizophrenia or other psychotic disorders

• Presence of psychotic symptoms at initial interview

• Schizoid or schizotypic personality disorder

• Positive urine screening for illicit substances, excluding cannabis

• Substance dependence in the preceding month (excluding nicotine or caffeine)

• Concomitant treatment with electroconvulsive therapy

• Unstable somatic pathology

• Clinically significant anomalies found during clinical examination, biological test or ECG

• Non-stabilized hypertension or hypertension > 180/100

• Known or suspected contra-indication for ketamine (includes interactions):

hypersensitivity to ketamine, hypertension, class IV cardiac insufficiency, history of stroke, hepatic or cutaneous porphyria, history of intracranial hypertension

Related Conditions & MeSH terms

• Suicidal Ideation

Intervention

Other:
• Baseline evaluation
Before perfusions begin, each patient will have a baseline evaluation including the following: the Columbia Suicide Severity Rating Scale (CSSRS), the Beck Scale for Suicide Ideation (BSSI), a physical pain VAS (visual analog scale), a mental pain VAS, the Clinical Global Impressions Scale (CGI-S), Beck's Hopeless scale (BHS), the Inventory of Depressive Symptomatology for the Clinician (IDS-C30), the Patient Rated Inventory of Side Effects (PRISE), the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS).

Drug:
• 1st perfusion of ketamine
A 1st perfusion of ketamine is performed: 0.5 mg/kg diluted in saline, administered over 40 minutes by intravenous (IV) pump and cardiorespiratory monitoring. (Day 0)
• 1st perfusion of saline
A 1st perfusion of saline is performed: the same volume of saline as in the ketamine arm, administered over 40 minutes by IV pump and cardiorespiratory monitoring. (Day 0)

Other:
• Follow-up between perfusions
Patients will be re-evaluated with a selection of questionnaires at 40 minutes, 120 minutes, 4 hours, and 24 hours after the end of the first perfusion, and then again at 48 hours after the end of the first perfusion and right before the second perfusion and then again Day 3, Day 4, Week 2, Week 4 and Week 6.

Drug:
• 2nd perfusion of ketamine
A 2nd perfusion of ketamine is performed: 0.5 mg/kg diluted in saline, administered over 40 minutes by intravenous (IV) pump and cardiorespiratory monitoring. (Day 2)
• 2nd perfusion of saline
A 2nd perfusion of saline is performed: the same volume of saline as in the ketamine arm, administered over 40 minutes by IV pump and cardiorespiratory monitoring. (Day 2)

Locations

Country	Name	City	State
France	CHU de Clermont Ferrand - Hôpital Gabriel-Montpied	Clermont Ferrand
France	CHRU de Lille - Hôpital Michel Fontan	Lille
France	CHRU de Montpellier - Hôpital Lapeyronie	Montpellier
France	Clinique Les Sophoras	Nîmes
France	CHRU de Nîmes - Hôpital Universitaire Carémeau	Nîmes Cedex 09
France	APHP - Hôpital Lariboisière	Paris
France	CMME Centre Hospitalier Sainte Anne	Paris
France	Centre Hospitalier Sainte-Anne	Paris cedex 14
France	CHRU de Tours - Clinique Psychiatrique Universitaire	Saint Cyr sur Loire

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	BSSI score	A suicidal ideation score measured using the BSS (Beck et al. 1979) in its hetero questionnaire form = 3 at 24 hours after the second infusion of ketamine or placebo (yes/no). A threshold = 3 separates the resolution of suicidal ideas from their persistence (Holi et al. 2005; DiazGranados et al. 2010).	Day 3
Secondary	The occurrence of a suicide attempt or a completed suicide (yes/no)		6 weeks
Secondary	Evaluation of the full spectrum of suicidality using the CSSRS		Baseline (Day-2 to Day 0)
Secondary	Evaluation of the full spectrum of suicidality using the CSSRS		Day 1
Secondary	Evaluation of the full spectrum of suicidality using the CSSRS		Day 2
Secondary	Evaluation of the full spectrum of suicidality using the CSSRS		Day 3
Secondary	Evaluation of the full spectrum of suicidality using the CSSRS		Day 4
Secondary	Evaluation of the full spectrum of suicidality using the CSSRS		Week 2
Secondary	Evaluation of the full spectrum of suicidality using the CSSRS		Week 4
Secondary	Evaluation of the full spectrum of suicidality using the CSSRS		Week 6
Secondary	The BSSI score		Baseline (Day-2 to Day 0)
Secondary	The BSSI score		40 min after end of 1st perfusion (Day 0)
Secondary	The BSSI score		120 min after end of 1st perfusion (Day 0)
Secondary	The BSSI score		4 hours after end of 1st perfusion (Day 0)
Secondary	The BSSI score		Day 1
Secondary	The BSSI score		Day 2
Secondary	The BSSI score		Day 4
Secondary	The BSSI score		Week 2
Secondary	The BSSI score		Week 4
Secondary	The BSSI score		Week 6
Secondary	Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Baseline (Day-2 to Day 0)
Secondary	Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		40 min after end of 1st perfusion (Day 0)
Secondary	Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		120 min after end of 1st perfusion (Day 0)
Secondary	Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		4 hours after end of 1st perfusion (Day 0)
Secondary	Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Day 1
Secondary	Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Day 2
Secondary	Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Day 3
Secondary	Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Day 4
Secondary	Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Week 2
Secondary	Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Week 4
Secondary	Evaluation of physical pain using a visual analog scale of 0 to 10 following a Lickert model		Week 6
Secondary	Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Baseline (Day-2 to Day 0)
Secondary	Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		40 min after end of 1st perfusion (Day 0)
Secondary	Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		120 min after end of 1st perfusion (Day 0)
Secondary	Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		4 hours after end of 1st perfusion (Day 0)
Secondary	Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Day 1
Secondary	Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Day 2
Secondary	Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Day 3
Secondary	Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Day 4
Secondary	Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Week 2
Secondary	Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Week 4
Secondary	Evaluation of mental pain using a visual analog scale of 0 to 10 following a Lickert model		Week 6
Secondary	Evaluation of despair using the Beck Hopelessness Scale		Baseline (Day-2 to Day 0)
Secondary	Evaluation of despair using the Beck Hopelessness Scale		Day 1
Secondary	Evaluation of despair using the Beck Hopelessness Scale		Day 2
Secondary	Evaluation of despair using the Beck Hopelessness Scale		Day 3
Secondary	Evaluation of despair using the Beck Hopelessness Scale		Day 4
Secondary	Evaluation of despair using the Beck Hopelessness Scale		Week 2
Secondary	Evaluation of despair using the Beck Hopelessness Scale		Week 4
Secondary	Evaluation of despair using the Beck Hopelessness Scale		Week 6
Secondary	Evaluation of depression by the clinician (IDS-C30)		Baseline (Day-2 to Day 0)
Secondary	Evaluation of depression by the clinician (IDS-C30)		4 hours after end of 1st perfusion (Day 0)
Secondary	Evaluation of depression by the clinician (IDS-C30)		Day 1
Secondary	Evaluation of depression by the clinician (IDS-C30)		Day 2
Secondary	Evaluation of depression by the clinician (IDS-C30)		Day 3
Secondary	Evaluation of depression by the clinician (IDS-C30)		Day 4
Secondary	Evaluation of depression by the clinician (IDS-C30)		Week 2
Secondary	Evaluation of depression by the clinician (IDS-C30)		Week 4
Secondary	Evaluation of depression by the clinician (IDS-C30)		Week 6
Secondary	Evaluation of somatic tolerance of ketamine using the Patient Rated Inventory of Side Effects (PRISE) throughout follow-up		Baseline (Day-2 to Day 0)
Secondary	Evaluation of somatic tolerance of ketamine using the Patient Rated Inventory of Side Effects (PRISE) throughout follow-up		Day 1
Secondary	Evaluation of somatic tolerance of ketamine using the Patient Rated Inventory of Side Effects (PRISE) throughout follow-up		Day 2
Secondary	Evaluation of somatic tolerance of ketamine using the Patient Rated Inventory of Side Effects (PRISE) throughout follow-up		Day 3
Secondary	Evaluation of somatic tolerance of ketamine using the Patient Rated Inventory of Side Effects (PRISE) throughout follow-up		Day 4
Secondary	Evaluation of psychic tolerance using the Young Mania Rating Scale (YMRS)		Baseline (Day-2 to Day 0)
Secondary	Evaluation of psychic tolerance using the Young Mania Rating Scale (YMRS)		Day 1
Secondary	Evaluation of psychic tolerance using the Young Mania Rating Scale (YMRS)		Day 2
Secondary	Evaluation of psychic tolerance using the Young Mania Rating Scale (YMRS)		Day 3
Secondary	Evaluation of psychic tolerance using the Young Mania Rating Scale (YMRS)		Day 4
Secondary	Evaluation of psychic tolerance using the Brief Psychiatric Rating Scale (BPRS)		Baseline (Day-2 to Day 0)
Secondary	Evaluation of psychic tolerance using the Brief Psychiatric Rating Scale (BPRS)		Day 1
Secondary	Evaluation of psychic tolerance using the Brief Psychiatric Rating Scale (BPRS)		Day 2
Secondary	Evaluation of psychic tolerance using the Brief Psychiatric Rating Scale (BPRS)		Day 3
Secondary	Evaluation of psychic tolerance using the Brief Psychiatric Rating Scale (BPRS)		Day 4
Secondary	Presence/absence of abnormal monitoring values throughout the study: hypertension	Any abnormal hypertension, pulse oxymetry or cardiac frequency values observed during the study will be noted.	6 weeks
Secondary	Presence/absence of abnormal monitoring values throughout the study: pulse oxymetry	Any abnormal hypertension, pulse oxymetry or cardiac frequency values observed during the study will be noted.	6 weeks
Secondary	Presence/absence of abnormal monitoring values throughout the study: cardiac frequency	Any abnormal hypertension, pulse oxymetry or cardiac frequency values observed during the study will be noted.	6 weeks
Secondary	Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Baseline (Day-2 to Day 0)
Secondary	Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		40 min after end of 1st perfusion (Day 0)
Secondary	Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		120 min after end of 1st perfusion (Day 0)
Secondary	Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		4 hours after end of 1st perfusion (Day 0)
Secondary	Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Day 1
Secondary	Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Day 2
Secondary	Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		120 min after end of 2nd perfusion (Day 2)
Secondary	Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Day 3
Secondary	Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Day 4
Secondary	Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Week 2
Secondary	Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Week 4
Secondary	Evaluation of the improvement of the patient's clinical condition using the Clinical Global Impression scale - Improvement (CGI-I)		Week 6
Secondary	The BSSI score	A suicidal ideation score measured using the BSS (Beck et al. 1979) in its self report questionnaire form = 3 at 24 hours after the second infusion of ketamine or placebo (yes/no). This scale is validated in French (de Man, Balkou & Iglesias 1987); a threshold = 3 separates the resolution of suicidal ideas from their persistence (Holi et al. 2005; DiazGranados et al. 2010)	24 hours after the last perfusion