NCT04721249

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
44

participants targeted

Target at P25-P50 for not_applicable major-depressive-disorder

Timeline
Completed

Started Jul 2021

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 15, 2021

Completed
7 days until next milestone

First Posted

Study publicly available on registry

January 22, 2021

Completed
5 months until next milestone

Study Start

First participant enrolled

July 1, 2021

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 30, 2023

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 30, 2024

Completed
Last Updated

May 10, 2024

Status Verified

May 1, 2024

Enrollment Period

2.3 years

First QC Date

January 15, 2021

Last Update Submit

May 9, 2024

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

  • Depression Severity

    measured with the Hamilton Depression Rating Scale (HAM-D)

    Change from baseline HAM-D score at 6 weeks

Secondary Outcomes (6)

  • Anxiety

    Change from baseline STAI score at 6 weeks

  • Anhedonia

    Change from baseline SHAPS score at 6 weeks

  • Neurocognition

    Change from baseline VLMT score at 6 weeks

  • Prefrontal glutamate concentration

    Change from baseline glutamate level at 6 weeks

  • Stress level

    Change from baseline cortisol level at 6 weeks

  • +1 more secondary outcomes

Study Arms (2)

Verum

ACTIVE COMPARATOR
Dietary Supplement: D-serine

Placebo

PLACEBO COMPARATOR
Dietary Supplement: Placebo

Interventions

D-serineDIETARY_SUPPLEMENT

Patients will receive four 500mg capsules of D-serine each day over a course of six weeks (two after breakfast and two after dinner).

Verum
PlaceboDIETARY_SUPPLEMENT

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.

Placebo

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Basel, Department of Psychiatry (UPK)

Basel, Canton of Basel-City, 4002, Switzerland

Location

Related Publications (1)

  • Sempach L, Schaub AC, Bruhl AB, Sterzer P, Lang UE, Schmidt A. Adjunctive d-serine treatment for major depressive disorder: A randomized clinical trial. J Affect Disord. 2025 Oct 15;387:119504. doi: 10.1016/j.jad.2025.119504. Epub 2025 May 26.

    PMID: 40436209DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Study Officials

  • André Schmidt, PD Dr

    University of Basel, Department of Psychiatry (UPK)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

January 15, 2021

First Posted

January 22, 2021

Study Start

July 1, 2021

Primary Completion

October 30, 2023

Study Completion

January 30, 2024

Last Updated

May 10, 2024

Record last verified: 2024-05

Data Sharing

IPD Sharing
Will not share

Locations

CH(1)