D-serine Supplementation for Depression

Study Overview
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Brief Summary
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The glutamate system is emerging as target for the development of novel antidepressant medication, in particular compounds modulating the NMDA receptor. While the NMDA receptor antagonist ketamine is an effective option for many treatment-restistant patients, it is also accompanied by dissociative and cognitive effects and also bears the risk to develop addiction, side effects that are significantly restricting its clinical utility. There is now compelling evidence of the antidepressant potential of D-serine, a NMDAR co-agonist. Compared to ketamine, D-serine goes along without any psychotomimetic effects or other side effects and thus might be a prom-ising novel antidepressant. This study represents the first randomized control trial to test the efficacy of D-serine as an adjuvant therapy in patients with depression and thereby adds to re-cent efforts to establish novel glutamatergic antidepressants. Besides clinical measures, this study also explores the biological mechanisms underlying D-serine's clinical effect.

Official Title
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A Randomized add-on Trial of D-serine for Depression

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Dietary Supplement: D-serine
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-60 Inpatients with a diagnosis of MDD with a current moderate-to-severe episode (HAM-D score > 16) (7) Treatment as usual (TAU) for depression. TAU for depression may include no treatment at all or standard pharmacotherapy (antidepressants and antipsychotics such as aripiprazole, risperidone or quetiapine) and / or psychotherapy. Able to read and understand study procedures and participant's information Exclusion Criteria: Other primary psychiatric diagnoses than MDD such as substance use and psychotic disorders Serious suicide attempts Contradiction for MRI (no pacemaker, MRI incompatible metal implants or splinters in the body, past heart/head surgery, past stroke/brain injury, claustrophobia) Pregnant or lactating women (pregnancy test)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Verum<br> | Dietary Supplement: D-serine<br>* Patients will receive four 500mg capsules of D-serine each day over a course of six weeks (two after breakfast and two after dinner).<br>|
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo<br>* Patients in the placebo group will receive four placebo capsules each day (two after breakfast and two after dinner). The placebo capsules will contain Mannotol / Mannitol-Silica (99.5/0.5, respectively) and will be indistinguishable from D-serine by matching colour, shape, size and packaging.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression Severity | measured with the Hamilton Depression Rating Scale (HAM-D) | Change from baseline HAM-D score at 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anxiety | measured with the State-and Trait-Anxiety Inventory (STAI) | Change from baseline STAI score at 6 weeks | 
| Anhedonia | measured with the Snaith-Hamilton-Pleasure Scale (SHAPS) | Change from baseline SHAPS score at 6 weeks | 
| Neurocognition | measured with the Verbal Learning and Memory Test (VLMT) | Change from baseline VLMT score at 6 weeks | 
| Prefrontal glutamate concentration | measured with magnetic resonance spectroscopy (MRS) | Change from baseline glutamate level at 6 weeks | 
| Stress level | measured with Cortisol awakening responses | Change from baseline cortisol level at 6 weeks | 
| Inflammation | measured with the blood levels of interleukin 1 and 6 | Change from baseline interleukin 1 and 6 level at 6 weeks |