The Effect of Intravenous Ketamine on Non Suicidal Self Injuries.

The Effect of Intravenous Ketamine on Non-suicidal Self-injuries in Women Suffering From Complex Post Traumatic Stress Disorder (cPTSD)

Non-suicidal self-injuries (NSSI) is a deliberate harm a person causes directly to their body, resulting in structural or functional damage, without suicidal ideation. This behavior is related to unbearable internal stress, thoughts, or mental pain, which NSSI assists in dismantling. To date, there is no generally approved therapy that assists in lowering NSSI. Ketamine is a sedative drug, presently at the focus of psychopharmacologic research, which was found to improve depression, when taken orally, and lower suicidal ideation, when given intravenously. Our aim is to assess the efficiency of intravenous ketamine in decreasing NSSI symptomology in women with a history of childhood sexual abuse presenting with such behavior. Participants will be recruited among hospitalized patients from the Tel-Aviv Medical Central psychiatric ward, who will present with either NSSI urges or behavior. The study design is a randomized control, double blind trial. Each patient will be assessed before, during, and after the trial by physical examination, blood tests and questionnaires. The patients will be randomized into research group (treated by ketamine and midazolam intravenously) or control group (treated intravenously via midazolam only). Our hypothesis is that treatment by intravenous ketamine will lower NSSI symptomology, and enable optimal treatment while being hospitalized.

Study Overview

• Status: Recruiting
• Conditions: Non Suicidal Self Injury
• Intervention / Treatment: Drug: Ketamine; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lior Dvorak, M.D.; Phone Number: 972527360974; Email: liordv@tlvmc.gov.il
• Study Contact Backup: Name: Michal Tevet, Ms.; Phone Number: 97236973685; Email: michaltev@tlvmc.gov.il

Study Locations

• Israel
  • Tel-Aviv, Israel
    • Recruiting
    • Psychiatric Service, Tel-Aviv Sourasky Medical Center
    • Contact: Miki Bloch, Ph.D.; Phone Number: 972-3-6974568
    • Principal Investigator: Miki Bloch, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age 18-65 y.o.
• Women
• Hospitalized
• Willing to sign the informed consent
• Fluent in Hebrew
• Reporting unbearable urge for self-injury and / or active NSSI behaviour) upon admittance, or on the preceding week.
• Not pregnant, nor breast feeding
• No history of drugs abuse
• No previous treatment with ketamine
• No psychotic disorder, nor severe physical condition (including unstable hypertension, arrhythmias or severe / active neurological condition)

Exclusion Criteria:

• Age < 18 year; Age >65 years
• Men
• Inability to sign informed consent, Non-Fluent in Hebrew.
• No report of NSSI, last NSSI event took place further than preceding week
• Active pregnancy or breast feeding
• History of drugs abuse
• Previous trial involving ketamine treatment during which no improvement was observed.
• Presence of psychotic disorder, and / or major physical condition (including unstable hypertension, arrhythmias or severe / active neurological condition).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Research: Ketamine + Midazolam; Research group will receive ketamine and midazolam.	Drug: Ketamine; Intravenous Ketamine, dose 0.5mg/kg in 100ml Sodium Chloride 0.9% over 40 minutes.; Drug: Midazolam; Intravenous Midazolam, dose 0.03mg/kg in 100ml Sodium Chloride 0.9% over 40 minutes.
Experimental: Control: Midazolam; Control group will receive midazolam.	Drug: Midazolam; Intravenous Midazolam, dose 0.03mg/kg in 100ml Sodium Chloride 0.9% over 40 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical measures - non suicidal self injuries symptoms	Change in non suicidal self injuries symptoms will be measured by Brief Non-Suicidal Self-Injury Assessment (BNSSI), which assess the quality of self injuries (method of injury, time since last injury, causes of injury, motivation of self injury and bodily areas where injuries are most common).	Four days prior to 1st treatment; after each intervention: 1 hour, 4 hours, 24 hours; next intervention will take place 3 days after (4 interventions altogether); 3 weeks post last intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical measures - biomarkers related to ketamine treatment - IL-6	Changes in specific biomarkers as a result of ketamine treatment: interleukin 6 (IL-6).	Four days prior to 1st treatment; 1 hour after 2nd intervention; 7 days later, 1 hour after 4th intervention; 3 weeks post last intervention.
Clinical measures - biomarkers related to ketamine treatment - hsCRP	Changes in specific biomarkers as a result of ketamine treatment: high sensitive C-Reactive Protein (hsCRP).	Four days prior to 1st treatment; 1 hour after 2nd intervention; 7 days later, 1 hour after 4th intervention; 3 weeks post last intervention.
Clinical measures - biomarkers related to ketamine treatment - BDNF	Changes in specific biomarkers as a result of ketamine treatment - Brain Dendritic Neurotrophic Factor (BDNF).	Four days prior to 1st treatment; 1 hour after 2nd intervention; 7 days later, 1 hour after 4th intervention; 3 weeks post last intervention.
Self reported questionnaires - depressive symptoms	Changes in depressive symptoms will be measured by Back Depression Inventory (BDI). Score scale from 1 to 40 points, higher score means more severe depression.	BDI will be taken four days prior to 1st treatment; 1 hour after 2nd intervention; 7 days later, 1 hour after 4th intervention; 3 weeks post last intervention.
Self reported questionnaires - anxiety symptoms	Changes in anxiety symptoms will be measured by Depression, Anxiety and Stress Scale (DASS-21 Items). Score scale from 0 to 63 points, higher score means more severe anxiety symptoms.	DASS-21 will be taken four days prior to 1st treatment; 3 weeks post last intervention.
Self reported questionnaires - Suicidal ideation	Changes in suicidal ideation will be measured by Columbia Suicide Severity Rating Scale (C-SSRS). This questionnaire assess severity of suicidal ideation, attempts and outcomes of attempted suicide.	C-SSRS will be taken four days prior to 1st treatment.
Self reported questionnaires - Suicidal ideation	Changes in suicidal ideation will be measured by Scale for Suicidal Ideation (SSI). Score scale from 0 to 38 points, higher score means increased severity of suicidal ideation.	SSI will be taken four days prior to 1st treatment; 1 hour after 2nd intervention; 7 days later, 1 hour after 4th intervention; 3 weeks post last intervention.
Self reported questionnaires - impulsivity	Changes in impulsive behavior will be measured by Barratt Impulsiveness Scale (BIS-11). This questionnaire assess impulsive behavior, with 30 items, including motor, attention and non-planning contributors. The factors are scored directly and reversibly, hence each factor assessed independently.	BIS-11 will be taken four days prior to 1st treatment four days; 3 weeks post last intervention.
Self reported questionnaires - well being	Patients well being will be measured by Well-Being Index (WHO 5). Higher score means greater well being.	WHO-5 will be taken four days prior to 1st treatment; 4 hour after 2nd intervention; 7 days later, 4 hour after 4th intervention; 3 weeks post last intervention.
Self reported questionnaires - Visual Analogue Scale (VAS)	During the treatments, there will be an on going assessment by visual analogue scale, composed of items regarding symptomatology of non suicidal self-injuries, suicidality, Depression and anxiety.	VAS will be after each intervention: 1 hour, 4 hours, 24 hours; next intervention will take place 3 days after (4 interventions altogether).
Clinical measures - adverse effects	During the treatments, the patient will be assessed for adverse effects of the infusion by ketamine side effects scale, including physical symptoms and psychotic symptoms.	Adverse effects questionnaire will be taken after each intervention: 1 hour, 4 hours; next intervention will take place 3 days after (4 interventions altogether).

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center
• Investigators: Principal Investigator: Miki Bloch, Prof., Tel Aviv University

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Anticipated): February 24, 2021
• Study Completion (Anticipated): February 24, 2024

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 23, 2020
• First Posted (Actual): January 27, 2020

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 23, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Ketamine, Midazolam, Non-Suicidal Self-Injury, Intravenous
• Additional Relevant MeSH Terms: Behavioral Symptoms; Wounds and Injuries; Self-Injurious Behavior; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam
• Other Study ID Numbers: 0724-018-TLV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No