The Effect of a Single Dose of Lamotrigine on Brain Function in Healthy Volunteers

Healthy Clinical Trial

Official title:

The Effect of a Single Dose of Lamotrigine on Brain Function in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04396938
• Other study ID #: R49749/RE003
• Status: Completed
• Phase: N/A
• Start date: May 10, 2017
• Est. completion date: August 30, 2019

Study information

• Verified date: September 2019
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: August 30, 2019
• Est. primary completion date: November 29, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Lamotrigine
Active Drug Capsule
• Placebos
Placebo Capsule

Locations

Country	Name	City	State
United Kingdom	University of Oxford	Oxford	Oxfordshire

Sponsors (1)

Lead Sponsor	Collaborator
University of Oxford

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neural function	fMRI resting state analysis	Data reporting and analysis to be completed within 1 year following study completion.
Primary	Neural function	fMRI task analysis	Data reporting and analysis to be completed within 1 year following study completion.
Primary	Neural function	fMRI checkerboard analysis	Data reporting and analysis to be completed within 1 year following study completion.
Secondary	Emotional Processing and Cognitive Function	Analysis of recognition of emotion in faces (an Emotional Test Battery component)	Data reporting and analysis to be completed within 6 months following study completion.
Secondary	Emotional Processing and Cognitive Function	Speed of negative self-descriptor processing (an Emotional Test Battery component)	Data reporting and analysis to be completed within 6 months following study completion.
Secondary	Emotional Processing and Cognitive Function	Emotional memory analysis (an Emotional Test Battery component)	Data reporting and analysis to be completed within 6 months following study completion.
Secondary	Emotional Processing and Cognitive Function	Beck Depression inventory (BDI) questionnaire analysis	Data reporting and analysis to be completed within 6 months following study completion.
Secondary	Emotional Processing and Cognitive Function	Positive and negative affect schedule (PANAS) questionnaire analysis	Data reporting and analysis to be completed within 6 months following study completion.
Secondary	Emotional Processing and Cognitive Function	Stait-trait anxiety inventory (STAI) questionnaire analysis	Data reporting and analysis to be completed within 6 months following study completion.