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

• ClinicalTrials.gov Identifier: NCT03915938
• Recruitment Status: Completed
• First Posted: April 16, 2019
• Last Update Posted: April 16, 2019
• Sponsor: Hospital de Clinicas de Porto Alegre
• Information provided by (Responsible Party): Hospital de Clinicas de Porto Alegre

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Acute Pain; Chronic Pain, Widespread; Schizophrenia	Drug: Ketamine; Drug: Placebo	Phase 2; Phase 3

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain: a Placebo-controlled Study in Healthy Male Subjects
• Actual Study Start Date: January 2, 2017
• Actual Primary Completion Date: November 30, 2017
• Actual Study Completion Date: November 30, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group S-Ketamine; 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; S-ketamine will be administered in precalculated infusion rates to obtain a plasmatic level of 60 ng/ml
Placebo Comparator: Group Placebo; A previously prepared identical solution containing only normal saline will be infused at the same infusion rates of group ketamine.	Drug: Placebo; Administered in an identical way than ketamine.

Outcome Measures

Primary Outcome Measures :

1. AUC of the grand averaged mean differences between ERPs elicited by target and non-target words [ Time Frame: up to 60 min ]
   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.

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Subjective euphoria rating [ Time Frame: up to 60 min ]
   Euphoria will be rated using an analogue visual scale ranging of 0 to 10.
2. Subjective sedation rating [ Time Frame: up to 60 min ]
   Sedation will be rated using an analogue visual scale ranging of 0 (completely awake) to 100 (sleeping).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Hospital de Clinicas de Porto Alegre

Investigators

• Principal Investigator: Wolnei Caumo, MD, PhD; Hospital de Clínicas de Porto Alegre

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Schwertner A, Zortea M, Torres FV, Ramalho L, Alves CFDS, Lannig G, Torres ILS, Fregni F, Gauer G, Caumo W. S-Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain: A Placebo- Controlled Study in Healthy Male Individuals. Front Neurosci. 2019 Sep 13;13:959. doi: 10.3389/fnins.2019.00959. eCollection 2019.

• Responsible Party: Hospital de Clinicas de Porto Alegre
• ClinicalTrials.gov Identifier: NCT03915938
• Other Study ID Numbers: 15-0019
• First Posted: April 16, 2019
• Last Update Posted: April 16, 2019
• Last Verified: January 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Hospital de Clinicas de Porto Alegre:

Ketamine; ERP; Oddball

Additional relevant MeSH terms:

Chronic Pain; Acute Pain; Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pain; Neurologic Manifestations; Ketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action