Reducing Psychological Side Effects of KetaminePhase 3NCT03831854
Lamotrigine in Reducing Psychologic Side-Effect of Perioperative Ketamine
A Phase 3 study testing Lamotrigine 300 MG and Ketamine in people with Reducing Psychological Side Effects of Ketamine, run by The Cleveland Clinic at 1 site in United States.
Trial summary
Patient will receive lamotrigine vs. placebo with small sips of water. Lamotrigine reaches peak level 1-4 hours after oral administration. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Reducing Psychological Side Effects of Ketamine
- What is being tested?
- Lamotrigine 300 MG and Ketamine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jan 2019to 31 Dec 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 -65 Years of age
- Planned overnight hospital stay
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Role of Lamotrigine in Reducing Psychologic Side-Effect of Perioperative Ketamine Use
Patient will receive lamotrigine vs. placebo with small sips of water. Lamotrigine reaches peak level 1-4 hours after oral administration.
Read the detailed 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.
- Being tested
- Lamotrigine 300 MG, Placebo, Ketamine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lamotrigine 300 MGDrug
Also called Lamictal 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).
PlaceboDrug
300 mg of oral Placebo
KetamineDrug
1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery
| Study group | Role | What they receive |
|---|---|---|
| lamotrigine | Active comparator | Patient will receive 300 mg of oral lamotrigine with small sips of water to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use. Receives: Drug: Lamotrigine 300 MG; Drug: Ketamine |
| Placebo | Placebo comparator | Patient will receive oral Placebo with small sips of water, to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use. Receives: Drug: Placebo; Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: in PACU (up to 90 minutes after ketamine infusion)
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.
Measured: Up to 90 minutes of PACU arrival
Secondary outcomes (3)
Total Opioid Consumption in PACU (mg)
Total cumulative opioid use (total IV morphine equivalents) in postoperative anesthesia care unit (PACU)
Measured: from entry to PACU to leaving PACU, up to 4 hours
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.
Measured: from entry to PACU to leaving PACU
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.
Measured: after surgery up to discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2019
- Study start24 Jan 2019
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Reducing Psychological Side Effects of KetamineStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomization without stratification
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03831854
- Sponsor's protocol ID
- 18-952
- Status last verified
- May 2021
- First submitted
- 3 Dec 2018
- Last updated
- 9 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to make subjects data available to outside researchers
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Lamotrigine in Reducing Psychologic Side-Effect of Perioperative Ketamine Use
- ClinicalTrials.gov ID
- NCT03831854
- Acronym / sponsor ID
- 18-952
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 24 Jan 2019 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 6 Feb 2019 (actual)
- Results
- Posted 9 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patient will receive lamotrigine vs. placebo with small sips of water. Lamotrigine reaches peak level 1-4 hours after oral administration.
Detailed 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- randomization without stratification
| Arm | Type | Receives |
|---|---|---|
| lamotrigine | Active comparator | Drug: Lamotrigine 300 MG, Drug: KetaminePatient will receive 300 mg of oral lamotrigine with small sips of water to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use. |
| Placebo | Placebo comparator | Drug: Placebo, Drug: KetaminePatient will receive oral Placebo with small sips of water, to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 18 -65 Years of age
- Planned overnight hospital stay
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lamotrigine 300 MGAlso: Lamictal 300 mg300 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). | Drug | lamotrigine |
| Placebo300 mg of oral Placebo | Drug | Placebo |
| Ketamine1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery | Drug | Placebo, lamotrigine |
Primary outcome
Psychologic Side-effects
Time frame: in PACU (up to 90 minutes after ketamine infusion)
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).
Number of Patients With Psychologic Disturbances-
Time frame: Up to 90 minutes of PACU arrival
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.
3 secondary outcomes
Total Opioid Consumption in PACU (mg)
Time frame: from entry to PACU to leaving PACU, up to 4 hours
Pain Score in PACU
Time frame: from entry to PACU to leaving PACU
Number of Patients Who Had PONV (Postoperative Nausea Vomiting)
Time frame: after surgery up to discharge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. There is no plan to make subjects data available to outside researchers
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lamotrigine 300 MG and Ketamine in people with Reducing Psychological Side Effects of Ketamine, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Psychologic Side-effects (time frame: in PACU (up to 90 minutes after ketamine infusion)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2021.