The Effect of Intravenous Ketamine on Non Suicidal Self Injuries.

Study Overview
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Brief Summary
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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.

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

Conditions
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Non Suicidal Self Injury

Intervention / Treatment
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* Drug: Ketamine
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized control, double blind trial
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketamine, Midazolam, Non-Suicidal Self-Injury, Intravenous