Ketamine-Induced Brain Changes and Their Modulation by Lamotrigine

NCT04156035 | Completed

• 1 other identifier: MSB-C001
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This study is firstly designed to investigate acute and delayed effects of a single dose of ketamine on functional brain changes during emotional and cognitive challenges and at rest. Secondly, it aims to investigate whether functional brain changes after ketamine require increased glutamatergic signaling and will accordingly be modulated after pretreatment with lamotrigine.

Conditions

Emotions

Outcome Measures

Primary Outcomes (1)

• Functional brain changes induced by emotional and cognitive challenge

  The primary endpoints of efficacy are the functional brain changes induced by emotional and cognitive challenge during ketamine infusion as compared to placebo and to the responses during ketamine infusion after Lamotrigine pretreatment during and after (post 24 hrs.) in following brain regions (bilateral): * Amygdala * Hippocampus * Dorsolateral Prefrontal Cortex * Anterior cingulate Cortex * Insula

  Measurements will occur during (acute) and 24h after (delayed) a single dose of ketamine

Secondary Outcomes (6)

• Changes in resting- state functional connectivity in default- mode network (DMN) and affective network (AN)

  Measurements will occur at baseline, during and 24h after a single dose of ketamine

• Changes in cerebral blood flow in predefined brain regions

  Measurements will occur during and 24h after a single dose of ketamine

• Association between functional brain changes during emotional and cognitive challenge and ketamine- induced dissociative state

  Measurements will occur during and 24h after a single dose of ketamine

• Association between changes in resting- state functional connectivity and ketamine- induced dissociative state

  Measurements will occur during and 24h after a single dose of ketamine

• Blood concentration of lamotrigine

  Measurements will occur at baseline as well as 0.30, 1:00, 1:30, 2:55 and 4h following drug administration

Study Arms (3)

Lamotrigine + Ketamine

EXPERIMENTAL

Pretreatment with lamotrigine will occur 2 hours before the ketamine infusion

Drug: Lamotrigine; Drug: Ketamine

Placebo + Ketamine

EXPERIMENTAL

Pretreatment with placebo will occur 2 hours before the ketamine infusion

Drug: Ketamine; Drug: Placebo Pretreatment

Placebo + Placebo

PLACEBO COMPARATOR

Pretreatment with placebo will occur 2 hours before the placebo infusion

Drug: Placebo Pretreatment; Drug: Placebo Infusion

Interventions

Lamotrigine DRUG

Orally; 300 mg

Lamotrigine + Ketamine

Ketamine DRUG

Intravenously; 0.12 mg/kg during the first minute followed by a continuous infusion of approximately 0.31 mg/kg/h over approx. 40 min

Lamotrigine + Ketamine; Placebo + Ketamine

Placebo Pretreatment DRUG

Lamotrigine Placebo

Placebo + Ketamine; Placebo + Placebo

Placebo Infusion DRUG

Ketamine Placebo

Placebo + Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• From 18 to 45 years of age, inclusive
• Body Mass Index (BMI) between 18.0 and 28.5 kg/m2, inclusive
• Healthy on the basis of physical examination, medical history, vital signs, clinical laboratory tests, and 12-lead ECG

You may not qualify if:

• Clinically relevant allergy or drug hypersensitivity
• A history of psychiatric or neurologic disorders
• Alcohol or substance dependence within the last 12 months from screening
• A positive urine drug screen at any visit
• Hypertonia, cardiac insufficiency, myocardial infarct within last 6 months
• Liver or renal function disorder
• Prescription of psychotropic medication within 28 days prior to screening
• Non-prescription medication, including analgesics and supplements such as vitamins and herbal supplements within 48 hours prior to the baseline visit

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Medical School Berlin

Berlin, 12247, Germany

Location

MeSH Terms

Interventions

Lamotrigine; Ketamine

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Simone Grimm, PhD

  Medical School Berlin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: November 7, 2019
• Study Start: March 10, 2020
• Primary Completion: December 10, 2020
• Study Completion: December 10, 2020
• Last Updated: March 29, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)