Memory Enhancement by Gamma-hydroxybutyrate vs. Trazodone in Major Depressive Disorder.

Study Overview
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Brief Summary
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30 healthy adults and 30 patients with major depressive disorder, will take part in three single-application pharmacological interventions (GHB vs. Trazodone vs. placebo p.o.) to test potential effects of these drugs on nocturnal memory consolidation. All participants will be assessed with mood state questionnaires, tests of emotional, procedural and declarative memory consolidation, polysomnography, EEG and neuroinflammatory biomarkers. At experimental nights, learning tasks are performed prior to sleep. The next morning, recalling tasks are performed. Each subject will pass through 5 study nights (1 screening, 1 adaptation and 3 experimental nights).

Official Title
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Memory Enhancement by Gamma-hydroxybutyrate vs. Trazodone in Major Depressive Disorder.

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: GHB
* Drug: Trazodone
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Arm 1 (healthy controls): Healthy participants, Non-smoker, Age 20-65 years Arm 2 (patients with depression): Diagnosis of major depression (DSM-V), Selective Serotonin-Reuptake-Inhibitor (SSRI) or Selective Serotonin-Noradrenalin-Reuptake-Inhibitor (SSNRI) medication, Age 20-65 years

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 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: healthy controls<br> | Drug: GHB<br>* 50 mg/kg GHB at one experimental night<br>Drug: Trazodone<br>* 1.5 mg/kg trazodone at one experimental night<br>Drug: Placebos<br>* placebo oral solution (placebo for GHB) and placebo pills (placebo for trazodon)<br>|
| Experimental: Major Depressive Disorder<br> | Drug: GHB<br>* 50 mg/kg GHB at one experimental night<br>Drug: Trazodone<br>* 1.5 mg/kg trazodone at one experimental night<br>Drug: Placebos<br>* placebo oral solution (placebo for GHB) and placebo pills (placebo for trazodon)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| slow wave sleep amount | slow wave sleep time (minutes) during the experimental night | 1 night | 
| performance in emotional memory consolidation tasks by Emotional Picture Memory Task (EPMT) | results in EPMT are measured as number of recognized pictures (1-150) | 10 hours after encoding | 
| performance in procedural memory consolidation tasks by Finger Sequence-Tapping Task (FSTT) | results in FSTT are measured as number of correct sequences typed in 30seconds | 10 hours after encoding | 
| performance in declarative memory consolidation tasks by Paired Word List Task (PAWL) | Results in PAWL are expressed as number of correct word pairs recalled (1-40). | 10 hours after encoding | 
| Blood levels of Brain Derived Neurotrophic Factor (BDNF). | Assessed in serum samples collected by venipuncture using a butterfly needle. Unit of measure as blood concentration (ng/l or mg/ml) | 9 hours after solid drug administration | 
| homeostatic sleep pressure by Psychomotor Vigilance Task | Results are measured in number of correct answers | 10 hours after solid drug administration | 
| homeostatic sleep pressure by N-back Task | Results are measured in number of correct answers | 10 hours after solid drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep quality assessed by Morgen Questionionnaire (MQ) | structured interview about sleep quality on the previous night. Subjektive sleep time will be assessed in minutes (0-480 minutes). Long sleep time will be a good outcome. Interview time of 5minutes. | at 8:00 a.m. after experimental night 1,2 and 3 | 
| Sleep quality assessed by Karolinska Schläfrigkeitsskala (SKK) | Subjects will report their subjective sleep pressure in a 1-10 points scale. Low values mean low sleep pressure and better therapy response. | at 8:00 a.m. after experimental night 1,2 and 3 | 
| Cortisol Saliva Response (CAR) | Cortisol concetration in Saliva (nmol/l) | 0minutes, 15minutes, 30minutes, 45minutes and 60minutes after awekening | 
| Score on Positive and Negative Affect Schedule (PANAS) | self-report questionnaire that consists of two 10-item scales to measure both positive and negative affect. Each item is rated on a 5-point scale of 1 (not at all) to 5 (very much) | 8 hours after solid drug administration |