The Sustained Effects of Ketamine

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.

Study Overview

• Status: Terminated
• Conditions: Mental Disorders
• Intervention / Treatment: Drug: Ketamine; Drug: Lamotrigine; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale Center for Clinical Investigation, Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-Ketamine Rs-fMRI Data	24 hours post infusion fMRI data	24 hours
Global Brain Connectivity	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.	24 hours

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Chadi Abdallah, MD, Yale University

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: March 9, 2016
• First Submitted That Met QC Criteria: March 9, 2016
• First Posted (Estimate): March 15, 2016

Study Record Updates

• Last Update Posted (Actual): July 2, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Ketamine; Lamotrigine
• Other Study ID Numbers: 1501015203