Lamotrigine in Reducing Psychologic Side-Effect of Perioperative Ketamine

Reducing Psychological Side Effects of Ketamine Clinical Trial

Official title:

The Role of Lamotrigine in Reducing Psychologic Side-Effect of Perioperative Ketamine Use

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03831854
• Other study ID #: 18-952
• Status: Completed
• Phase: Phase 3
• Start date: January 24, 2019
• Est. completion date: December 31, 2020

Study information

• Verified date: May 2021
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patient will receive lamotrigine vs. placebo with small sips of water. Lamotrigine reaches peak level 1-4 hours after oral administration.

Description:

1:1 randomization without stratification use web-based software (Redcap) before surgery. Allocation will be concealed from the patient, the nurse, the operating room team. Both patient and the operating room team will be blinded to the treatment allocation (double blind).

Standard preoperative care as per anesthesia care team. Patient will receive lamotrigine vs. placebo with small sips of water. Lamotrigine reaches peak level 1-4 hours after oral administration. Single dose lamotrigine is safe and is not associated with rash.

Standard intraoperative care as per the anesthesia care team. All patients will receive Ketamine 1 mg/kg at induction. Ketamine 5mcg/kg/min will be started at induction and stopped at the end of surgery.

Standard postoperative care as per PACU team. The psychologic side-effects will be measured using Brief Psychiatric Rating Scale (BPRS) using an online tool.

Research fellow will receive standardized training in administering BPRS from Dr. Amit Anand using structured material. Dr. Anand has used this training for other current research projects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 18 -65 Years of age

• Planned overnight hospital stay

Exclusion Criteria:

• Pregnant and planning to become pregnant

• No known History of seizure

• No known History of Schizophrenia

• No known History of unstable angina

• Patients taking Antiepileptic medications

• Known history of Lamotrigine intake in past.

• Any history of allergic reaction to lamotrigine in the past.

Related Conditions & MeSH terms

• Reducing Psychological Side Effects of Ketamine

Intervention

Drug:
• Lamotrigine 300 MG
300 mg of oral Lamotrigine. One of the key studies in this area was reported at the Society of Neuroscience meeting in 1997 and later published in the Archives of General Psychiatry. This study reported that, in healthy subjects 300 mg oral lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P<.001).31 Furthermore lamotrigine increased the immediate mood-elevating effects of ketamine (P<.05).
• Placebo
300 mg of oral Placebo
• Ketamine
1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Daily Average Opioid Use During Hospital Stay	The average daily opioid use (mg) during the hospital stay.	from admission up to discharge
Other	Opioid Related Side-effects (ORSDS)-POD1	ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means worse outcome. This one measure ORSDS at postoperative day 1	postoperative day 1
Other	Opioid Related Side-effects (ORSDS)-POD2	ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means a worse outcome. This one measure ORSDS at postoperative day 2.	postoperative day 2
Other	PACU Length of Stay, Hours	Hours spent in PACU (Postanesthesia Care Unit).	in PACU
Primary	Psychologic Side-effects	The primary outcome of psychologic side-effects was measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score).	in PACU (up to 90 minutes after ketamine infusion)
Primary	Number of Patients With Psychologic Disturbances-	The psychologic side-effects were measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score). Patients who had a total score of 4 (all symptoms not present) were determined as not having psychologic disturbance and patients who had a total score of > 4 (having any symptoms present) were determined as having psychologic disturbance.	Up to 90 minutes of PACU arrival
Secondary	Total Opioid Consumption in PACU (mg)	Total cumulative opioid use (total IV morphine equivalents) in postoperative anesthesia care unit (PACU)	from entry to PACU to leaving PACU, up to 4 hours
Secondary	Pain Score in PACU	Pain score was scaled from 0-10 where 0 means no pain and 10 means most pain. The time-weighted average of pain scores was used if the pain score was measured multiple times.	from entry to PACU to leaving PACU
Secondary	Number of Patients Who Had PONV (Postoperative Nausea Vomiting)	PONV was measured through Postoperative Nursing Progress Record, where nausea vomiting severity was recorded as 0 (none), 1 (mild), 2 (moderate), 3 (severe). Patients whose score was 0 were determined as not having PONV and patients whose score was positive were determined as having PONV.	after surgery up to discharge