The Sustained Effects of Ketamine

• Sponsor: Yale University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02708849
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arms: 2
• Duration (Months): 57
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to characterize the effects of a single, sub-anesthetic dose of ketamine in rs-fMRI in healthy subjects. Post-ketamine rs-fMRI data will demonstrate a pattern of increased global brain connectivity (GBC) in fronto-temporal cortex.

Condition or Disease	Intervention/Treatment	Phase
Mental Disorders	Drug: Ketamine; Drug: Lamotrigine; Drug: Placebo	Phase 1

Detailed Description

In this study, healthy participants will be randomized into one of two parallel groups: (a) open-label ketamine and active lamotrigine, or (b) open-label ketamine with a matched-placebo control (i.e., sugar pill). All participants will complete a baseline rs-fMRI approximately 1-week prior to the ketamine infusion and a follow-up rs-fMRI 24-hours post-infusion. The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion to occur during the MRS scan. Participants will be administered lamotrigine (300 mg oral dose) or the matched-placebo control about 2-hours prior to the start of the infusion.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Basic Science
• Official Title: The Sustained Effects of Ketamine
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Mar 1, 2020
• Actual Study Completion Date: Mar 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketamine plus lamotrigine	Drug: Ketamine; The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion; Drug: Lamotrigine; lamotrigine (300 mg oral dose) or the matched-placebo control about 2-hours prior to the start of the infusion of ketamine
Placebo Comparator: ketamine plus placebo	Drug: Ketamine; The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion; Drug: Placebo; oral dose placebo

Outcome Measures

Primary Outcome Measures

1. Post-Ketamine Rs-fMRI Data [24 hours]

   24 hours post infusion fMRI data

2. Global Brain Connectivity [24 hours]

   Participants will be randomized into one of two parallel groups-ketamine+lamotrigine or ketamine+placebo-and will complete pre- and post-ketamine rs-fMRI. The hypothesis is that post-ketamine rs-fMRI data will demonstrate a pattern of increased global brain connectivity (GBC) in fronto-temporal cortex. Insufficient number of participants for data collection.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female between the ages of 21-65 years. Females will be included if they are not pregnant and agreed to utilize a barrier method contraceptive (e.g., condom or diaphragm with spermicide) tubal ligation, abstinence, or partner with vasectomy) or if post-menopausal for at least 1 year, or surgically sterile.

• Able to provide written informed consent according to Yale HIC guidelines.

• Agree to refrain from elective surgeries (including dental) for a 2-week period following study drug.

• Able to read and write English as a primary language.

Exclusion Criteria:

• Personal history of mood, anxiety, or psychotic axis I DSM-IV disorders confirmed after comprehensive psychiatric evaluation.

• Any history of serious medical or neurological illness.

• Any signs of major medical or neurological illness on examination or as a result of ECG screening or laboratory studies.

• A first-degree family member with history of schizophrenia.

• Lifetime history of psychoactive substance or alcohol dependence or substance or alcohol abuse (other than nicotine or caffeine abuse), or drinking more that 5 drinks/week during the last year.

• Abnormality on physical examination. A subject with a clinical abnormality may be included only if the study physician considers the abnormality will not introduce additional risk factors and will not interfere with the study procedure (e.g. uncontrolled hypertension, hyperthyroidism, or hypothyroidism will be excluded).

• A positive pre-study (screening) urine drug screen or, at the study physician's discretion on any drug screens given before the scans.

• Pregnant or lactating women or a positive urine pregnancy test for women of child-bearing potential at screening or prior to any imaging day.

• Positive HIV or Hepatitis B/C tests. This test will take place at the screening visit. Subjects will be invited back either for their next study visit or for a HIV/Hep debriefing session. A study clinician will inform them in person of the results. They will be given access to counselling and advised of the appropriate next steps.

• Has received either prescribed or over-the-counter (OTC) centrally active medicine or herbal supplements within the week prior to the MRI scan. Subjects who have taken OTC medication or herbal supplements may still be entered into the study, if, in the opinion of the principal/co-investigator, the medication received will not interfere with the study procedures or compromise safety.

• Any history indicating learning disability, mental retardation, or attention deficit disorder.

• Known sensitivity to ketamine.

• Known sensitivity to lamotrigine.

• Body weight of 250 pounds or greater.

• History of claustrophobia.

• Presence of cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-MRI screening questionnaire.

• Donation of blood in excess of 500 mL within 56 days prior to dosing.

• History of sensitivity to heparin or heparin-induced thrombocytopenia.

• Resting blood pressure lower than 90/60 or higher than 150/90, or resting heart rate lower than 45/min or higher than 100/min.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Center for Clinical Investigation, Yale University	New Haven	Connecticut	United States	06519

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Chadi Abdallah, MD, Yale University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 8, 2018

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02708849
• Other Study ID Numbers: 1501015203
• First Posted: Mar 15, 2016
• Last Update Posted: Jul 2, 2020
• Last Verified: Jun 1, 2020

• Additional relevant MeSH terms: Mental Disorders; Lamotrigine; Ketamine

Study Results

Participant Flow

Arm/Group Title	Ketamine Plus Lamotrigine	Ketamine Plus Placebo
Arm/Group Description	Ketamine: The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion Lamotrigine: lamotrigine (300 mg oral dose) or the matched-placebo control about 2-hours prior to the start of the infusion of ketamine	Ketamine: The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion Placebo: oral dose placebo
Period Title: Overall Study
STARTED	2	1
COMPLETED	1	1
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Ketamine Plus Lamotrigine	Ketamine Plus Placebo	Total
Arm/Group Description	Ketamine: The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion Lamotrigine: lamotrigine (300 mg oral dose) or the matched-placebo control about 2-hours prior to the start of the infusion of ketamine	Ketamine: The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion Placebo: oral dose placebo	Total of all reporting groups
Overall Participants	2	1	3
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	NA (NA)	NA (NA)	40 (7.8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	2 100%	1 100%	3 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	2 100%	1 100%	3 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 100%	0 0%	2 66.7%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 100%	1 33.3%
Region of Enrollment (participants) [Number]
United States	2 100%	1 100%	3 100%

Outcome Measures

1. Primary Outcome

Title	Post-Ketamine Rs-fMRI Data
Description	24 hours post infusion fMRI data
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Imaging data were not extracted to protect confidentiality of participants.

Arm/Group Title	Ketamine Plus Lamotrigine	Ketamine Plus Placebo
Arm/Group Description	Ketamine: The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion Lamotrigine: lamotrigine (300 mg oral dose) or the matched-placebo control about 2-hours prior to the start of the infusion of ketamine	Ketamine: The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion Placebo: oral dose placebo
Measure Participants	0	0

2. Primary Outcome

Title	Global Brain Connectivity
Description	Participants will be randomized into one of two parallel groups-ketamine+lamotrigine or ketamine+placebo-and will complete pre- and post-ketamine rs-fMRI. The hypothesis is that post-ketamine rs-fMRI data will demonstrate a pattern of increased global brain connectivity (GBC) in fronto-temporal cortex. Insufficient number of participants for data collection.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Insufficient number of participants for data collection

Arm/Group Title	Ketamine Plus Lamotrigine	Ketamine Plus Placebo
Arm/Group Description	Ketamine: The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion Lamotrigine: lamotrigine (300 mg oral dose) or the matched-placebo control about 2-hours prior to the start of the infusion of ketamine	Ketamine: The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion Placebo: oral dose placebo
Measure Participants	0	0

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Ketamine Plus Lamotrigine		Ketamine Plus Placebo
Arm/Group Description	Ketamine: The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion Lamotrigine: lamotrigine (300 mg oral dose) or the matched-placebo control about 2-hours prior to the start of the infusion of ketamine		Ketamine: The subanesthetic dose of ketamine (0.23mg/kg bolus followed by 0.58mg/kg infusion over approximately 60 minutes) will be administered via intravenous infusion Placebo: oral dose placebo
All Cause Mortality
	Ketamine Plus Lamotrigine		Ketamine Plus Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Serious Adverse Events
	Ketamine Plus Lamotrigine		Ketamine Plus Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Ketamine Plus Lamotrigine		Ketamine Plus Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.