Mechanism of tDCS-induced Learning Enhancement - the Role of Serotonin

Study Overview
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Brief Summary
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The aim of this study is to assess whether the application of a selective serotonin reuptake inhibitor (SSRI) enhances and prolongs the learning enhancement achieved by anodal transcranial direct current stimulation (atDCS). For this, young and older healthy subjects will be tested with a well established learning paradigm. Results of this study may help to support the application of atDCS also in patients, e.g. with dementia or mild cognitive impairment.

Official Title
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Mechanism of tDCS-induced Learning Enhancement - the Role of Serotonin

Conditions
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Healthy Young and Older Adults

Intervention / Treatment
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* Procedure: tDCS
* Drug: Citalopram
* Other: sham-tDCS + placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: right handedness unobtrusive neuropsychological screening ability to provide written informed consent no pathological findings in head MRI age: 18 to 35 years (young adults) or 50-80 years (older adults) Highly effective contraception (Pearl Index < 1) or reliable abstinence from any heterosexual relationships in women of childbearing potential Exclusion Criteria: severe internal or psychiatric disease (especially depression or suicidal thoughts) epilepsy cognitive impairment (< SD under age adjusted norm in neuropsychological testing) concurrent taking of serotonin precursors (tryptophan, 5-HTP) or MAO inhibitors concurrent taking of tramadol or triptans concurrent taking of pimozide or linezolid concurrent taking of other drugs prolonging the QT-interval long-QT-syndrome hypokalemia or hypomagnesemia known intolerance of the study medication claustrophobia or metallic implants, tattoos (MRI exclusion criteria) pregnancy or lactation participation in another drug-interventional clinical trial within the last month or during the entire study probands that are placed in an institution due to official or judicial order non-agreement to save and transmit pseudonymised study data within the clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tDCS + SSRI<br> | Procedure: tDCS<br> <br> * Other names: transcranial direct current stimulation;Drug: Citalopram<br> <br> * Other names: SSRI;|
| Placebo Comparator: tDCS + placebo<br> | Procedure: tDCS<br> <br> * Other names: transcranial direct current stimulation;|
| Sham Comparator: sham-tDCS + SSRI<br> | Drug: Citalopram<br> <br> * Other names: SSRI;|
| Placebo Comparator: sham-DCS + placebo<br> | Other: sham-tDCS + placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recall score after learning under tDC stimulation + SSRI compared to learning under tDC stimulation + placebo. | Recall score immediately after learning phase (=training of visual-spatial abilities) under tDC stimulation + SSRI application compared to learning under tDC stimulation + placebo. | immediately after end of learning phase (approx. 1 hour) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prolongation of the atDCS induced learning enhancement by SSRI | Measurement of recall scores on the evening of the same day after the learning phase (+tDCS + SSRI), the morning of the day after and 1 week later in order to assess the prolongation of atDCS induced learning enhancement by the SSRI. | 1 week | 
| Increase of learning enhancement by atDCS + placebo or sham-tDCS + SSRI vs. sham-tDCS + placebo | Measurement of recall scores directly after learning phase after application of atDCS + placebo or sham-tDCS + SSRI vs. sham-tDCS + placebo. | immediately after learning phase (approx. 1 hour) | 
| prolongation of learning enhancement by atDCS + placebo or sham-tDCS + SSRI vs. sham-tDCS + placebo | Measurement of recall scores on the evening of the same day of learning phase, the morning of the day after and 1 week later under application of atDCS + placebo or sham-tDCS + SSRI vs. sham-tDCS + placebo, in order to assess prolongation of learning enhancement by SSRI. | 1 week | 
| genotyping of learning related polymorphisms | To assess predictors of SSRI-enhanced brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF, Val66Met, COMT, Val158Met, KIBRA, rs17070145, 5-Hydroxytryptamine transporter). | once | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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young, transcranial direct current stimulation (tDCS), selective serotonin reuptake inhibitor (SSRI), older adults