Clinical trial NCT04396938: The Effect of a Single Dose of Lamotrigine on Brain Function in Healthy Volunteers
Official title: The Effect of a Single Dose of Lamotrigine on Brain Function in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2020-05-21
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study will test whether a single dose of Lamotrigine (300mg) exerts significant effects on emotional processing, cognitive ability and neural activity in healthy volunteers compared to placebo.

Detailed description: Glutamate has been implicated in the aetiology of mood disorders and there is current interest in developing novel agents targeting this system. However, the role of glutamate in human emotional function is relatively unknown. Lamotrigine's pharmacological profile involves a blockade of voltage-gated sodium channels, leading to an inhibition in the release of glutamate and resulting in a general inhibitory effect on cortical neuronal function.

The current study plans to investigate the effects of modifying glutamate on emotional processing, cognitive function and neural activity. For this, 36 healthy volunteers will be recruited to the study and randomised to receive a single dose of lamotrigine (300 mg) or placebo. Two hours after drug administration, the effects of emotional processing via the use of cognitive tasks will be assessed using fMRI. This will be followed by an emotional test battery that will measure aspects of cognitive function as well.

Eligibility criteria: Inclusion Criteria:

* Male or female
* Aged 18-40 years
* Willing and able to give informed consent for participation in the study
* Sufficiently fluent English to understand and complete the task

Exclusion Criteria:

* Current usage of psychoactive medication
* Current usage of the contraceptive pill
* Any past or current Axis 1 DSM-IV psychiatric disorder
* Significant medical condition
* Current pregnancy or breastfeeding
* Current or past history of drug or alcohol dependency
* Participation in a psychological or medical study involving the use of medication within the last 3 months
* Previous participation in a study using the same, or similar, emotional processing tasks
* Smoker \> 5 cigarettes per day
* Typically drinks \> 6 caffeinated drinks per day
* Takes folic acid supplements
* History of recurrent allergies and rashes
* Contraindication to MRI (e.g. claustrophobia and metallic implants)

Primary outcomes:
measure: Neural function
timeFrame: Data reporting and analysis to be completed within 1 year following study completion.
measure: Neural function
timeFrame: Data reporting and analysis to be completed within 1 year following study completion.
measure: Neural function
timeFrame: Data reporting and analysis to be completed within 1 year following study completion.
Secondary outcomes:
measure: Emotional Processing and Cognitive Function
timeFrame: Data reporting and analysis to be completed within 6 months following study completion.
measure: Emotional Processing and Cognitive Function
timeFrame: Data reporting and analysis to be completed within 6 months following study completion.
measure: Emotional Processing and Cognitive Function
timeFrame: Data reporting and analysis to be completed within 6 months following study completion.
measure: Emotional Processing and Cognitive Function
timeFrame: Data reporting and analysis to be completed within 6 months following study completion.
measure: Emotional Processing and Cognitive Function
timeFrame: Data reporting and analysis to be completed within 6 months following study completion.
measure: Emotional Processing and Cognitive Function
timeFrame: Data reporting and analysis to be completed within 6 months following study completion.
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: University of Oxford
state: Oxfordshire
Study officials:
affiliation: University of Oxford
name: Catherine Harmer, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Calabrese JR, Huffman RF, White RL, Edwards S, Thompson TR, Ascher JA, Monaghan ET, Leadbetter RA. Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials. Bipolar Disord. 2008 Mar;10(2):323-33. doi: 10.1111/j.1399-5618.2007.00500.x.
citation: Deakin JF, Lees J, McKie S, Hallak JE, Williams SR, Dursun SM. Glutamate and the neural basis of the subjective effects of ketamine: a pharmaco-magnetic resonance imaging study. Arch Gen Psychiatry. 2008 Feb;65(2):154-64. doi: 10.1001/archgenpsychiatry.2007.37.
citation: Doyle OM, De Simoni S, Schwarz AJ, Brittain C, O'Daly OG, Williams SC, Mehta MA. Quantifying the attenuation of the ketamine pharmacological magnetic resonance imaging response in humans: a validation using antipsychotic and glutamatergic agents. J Pharmacol Exp Ther. 2013 Apr;345(1):151-60. doi: 10.1124/jpet.112.201665. Epub 2013 Jan 31.
citation: Murphy SE, Norbury R, O'Sullivan U, Cowen PJ, Harmer CJ. Effect of a single dose of citalopram on amygdala response to emotional faces. Br J Psychiatry. 2009 Jun;194(6):535-40. doi: 10.1192/bjp.bp.108.056093.