Ketamine-Induced Brain Changes and Their Modulation by Lamotrigine
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ClinicalTrials.gov Identifier: NCT04156035 |
Recruitment Status :
Completed
First Posted : November 7, 2019
Last Update Posted : March 29, 2021
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Tracking Information | |||||||
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First Submitted Date ICMJE | October 23, 2019 | ||||||
First Posted Date ICMJE | November 7, 2019 | ||||||
Last Update Posted Date | March 29, 2021 | ||||||
Actual Study Start Date ICMJE | March 10, 2020 | ||||||
Actual Primary Completion Date | December 10, 2020 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Functional brain changes induced by emotional and cognitive challenge [ Time Frame: Measurements will occur during (acute) and 24h after (delayed) a single dose of ketamine ] 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):
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Ketamine-Induced Brain Changes and Their Modulation by Lamotrigine | ||||||
Official Title ICMJE | A Trial to Study Acute and Delayed Effects of a Single Dose of Ketamine on Functional Brain Changes During Emotional/ Cognitive Challenges and at Rest and Their Modulation by Lamotrigine in Healthy Subjects | ||||||
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. | ||||||
Detailed Description | Despite the rapid antidepressant effects of ketamine, its increasing use as an AD and the recent (2019) FDA approval of ketamine nasal spray as medication for treatment-resistant depression, the exact neurobiological mechanisms underlying its effects remain unclear. There are numerous reasons, why so far there has been no coherent explanatory framework. Most previous studies focused on investigating a single domain such as functional connectivity (e.g. Deakin et al., 2008; Scheidegger et al., 2012), functional brain changes to either cognitive (e.g. Honey et al., 2005; Driessen et al., 2013) or emotional challenge (e.g. Scheidegger & Grimm et al., 2016; Reed et al., 2019), perfusion (e.g. Pollack et al., 2015), magnetic fields (Salvadore et al., 2010) or neurotransmitter concentrations (e.g. Abdallah et al., 2018). Small sample sizes of as little as 8 subjects, the lack of a control group, the limited number of timepoints for measurement of the above-mentioned parameters, and the failure to modulate glutamatergic signalling after ketamine further limit the informative value of previous findings. What is therefore urgently needed in order to better understand the mechanisms of ketamine, is a study that combines neuroimaging in several modalities, investigates acute as well as delayed effects of ketamine and applies an approach to modulate glutamatergic signaling after ketamine. Accordingly, this study is designed to investigate acute and delayed effects of a single dose of ketamine on functional brain changes during emotional and cognitive challenge and at rest as well as to investigate the functional significance of increased glutamatergic signalling after ketamine. Measurement of functional brain changes will occur during (acute) and 24 hrs. after a single dose of ketamine, as differential effects are hypothesized. To modulate glutamatergic signaling after ketamine, a lamotrigine pretreatment protocol will be used. It is hypothesized that functional brain changes previously linked to ketamine require increased glutamatergic signaling and will be attenuated by pretreatment with lamotrigine. To test these hypotheses, we will implement a randomized, placebo-controlled, parallel-group design with 3 treatment conditions (lamotrigine + ketamine, placebo + ketamine, placebo + placebo). All subjects will undergo two scanning sessions (acute + post 24 hrs.). In order to include baseline values as covariates in the analyses, imaging will begin 10 minutes before infusion of ketamine/placebo. Pretreatment with lamotrigine or matching placebo will occur 2 hours before the ketamine/placebo infusion. Blood samples will be taken at 0:30, 1:00, 1:30, 2:55 and 4 hours following oral drug administration to determine the plasma pharmacokinetics of lamotrigine, and at 40 minutes after commencing ketamine infusion to confirm target ketamine plasma levels. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Not Applicable | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Basic Science |
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Condition ICMJE | Emotions | ||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Completed | ||||||
Actual Enrollment ICMJE |
75 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Actual Study Completion Date ICMJE | December 10, 2020 | ||||||
Actual Primary Completion Date | December 10, 2020 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Main Inclusion Criteria:
Main Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 45 Years (Adult) | ||||||
Accepts Healthy Volunteers ICMJE | Yes | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | Germany | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT04156035 | ||||||
Other Study ID Numbers ICMJE | MSB-C001 | ||||||
Has Data Monitoring Committee | Not Provided | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Simone Grimm, Medical School Berlin | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | Charite University, Berlin, Germany | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE | Boehringer Ingelheim | ||||||
Investigators ICMJE |
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PRS Account | Charite University, Berlin, Germany | ||||||
Verification Date | March 2021 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |