Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain

Study Overview
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Brief Summary
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This is a clinical trial that intend to determine the effects of S-ketamine on event-related potentials associated with semantic affective pain-processing

Detailed Description
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Ketamine is a unique anesthetic with neural effects that are distinct from more commonly-used γ-aminobutyric acid agonists. Evidence suggest that analgesic effect of ketamine is primarily related to the affective than the sensorial aspects of pain interpretation. The investigators investigated whether ketamine, a noncompetitive NMDA antagonist, would modify the perceived emotional valence of pain-related words when compared to non-pain-related ones in healthy volunteers. Using a single session double-blind parallel placebo-controlled design, 24 healthy volunteers were randomized to receive intravenous S-ketamine (n=12) or placebo (n=12). During infusion (plasmatic target of 60 ng/ml), the effects of ketamine were recorded using EEG and oddball behavioral data was monitored. Evoked potentials (N200 and P300 components) were recorded during performance of a semantic written word oddball task containing pain-related (targets) and non-pain-related words (standards). Expected results: The findings of this study can help in the understanding of neurophysiologic mechanisms involved in ketamine's effects both in psychiatric diseases as in the treatment of postoperative acute and chronic pain.

Official Title
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Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain: a Placebo-controlled Study in Healthy Male Subjects

Conditions
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Acute Pain, Chronic Pain, Widespread, Schizophrenia

Intervention / Treatment
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* Drug: Ketamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male healthy subjects with higher education level Exclusion Criteria: do not understand Portuguese language obese patients (BMI > 27 kg/m2) use of NSAID, steroids, analgesics, anticonvulsant drugs, as well as alpha and beta-blockers score ≥ 13 on Beck II Questionnaire sleep deprivation in the night before evaluation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group S-Ketamine<br>S-Ketamine will be diluted in normal saline and administrated in a target controlled infusion using an infusion pump to obtain a plasma target of 60 ng/ml according to Domino's model. Infusion will start during the interval between the 3rd and 4th blocks of the task. | Drug: Ketamine<br>* S-ketamine will be administered in precalculated infusion rates to obtain a plasmatic level of 60 ng/ml<br>|
| Placebo Comparator: Group Placebo<br>A previously prepared identical solution containing only normal saline will be infused at the same infusion rates of group ketamine. | Drug: Placebo<br>* Administered in an identical way than ketamine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of the grand averaged mean differences between ERPs elicited by target and non-target words | EEG will be recorded during all task time. The main outcome will be the area under de curve (AUC) of the grand averaged mean differences between event-related potencials (ERPs) elicited by target and non-target words at 100-200, 300-500 and 800-900 ms after stimulus presentation for parietal electrophysiological signal (Pz). The ERPs represent the averaged voltage of several trials. | up to 60 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Word ratings related to the semantic valence | After viewing each word, volunteers were asked to classify them according to the semantic valence in the following categories: positive, negative or neutral. | up to 60 min | 
| Response times (behavioural oddball data) | Response times to word classification in oddball task | up to 60 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketamine, ERP, Oddball