NCT04977674 (GO-MARK) is a EARLY_PHASE1 clinical trial of Naltrexone in Depressive Disorder, Treatment-Resistant, sponsored by King's College London.

Who is sponsoring NCT04977674?

NCT04977674 is sponsored by King's College London.

What drugs are being tested in NCT04977674?

Interventions in NCT04977674: Naltrexone, Placebo, Ketamine.

What condition does NCT04977674 study?

NCT04977674 studies Depressive Disorder, Treatment-Resistant.

Is NCT04977674 still recruiting?

NCT04977674 is currently completed. Last updated 2 March 2023.

Last reviewed 2023-03-02 · How we verify

NCT04977674: GO-MARK

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

Glutamate and Opioid Mechanisms of Antidepressant Response to Ketamine

Completed EARLY_PHASE1 Last updated 2 March 2023

What this trial tests

EARLY_PHASE1 trial testing Naltrexone in Depressive Disorder, Treatment-Resistant in 27 participants. Completed in 20 February 2023.

Timeline

27 September 2021

Primary endpoint
13 February 2023

20 February 2023

Quick facts

Lead sponsor	King's College London
Phase	EARLY_PHASE1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	quadruple
Primary purpose	basic science
Enrollment	27
Start date	27 September 2021
Primary completion	13 February 2023
Estimated completion	20 February 2023
Sites	1 location across United Kingdom

Drugs / interventions tested

Naltrexone — full drug profile →
Placebo
Ketamine (ketamine) — full drug profile →

Conditions studied

Depressive Disorder, Treatment-Resistant — all drugs for Depressive Disorder, Treatment-Resistant →

Sponsor

King's College London

Who can join

Adults 18 to 50, any sex, with Depressive Disorder, Treatment-Resistant. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The overarching aim of this research is to determine the acute effects of ketamine on brain glutamate, functional connectivity and cerebral blood flow in treatment-resistant depression, explore whether the effects are attenuated by the opioid receptor antagonist naltrexone and relate these findings to antidepressant response.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

The opioid system in depression.
Jelen LA, Stone JM, Young AH, Mehta MA. · · 2022 · cited 56× · PMID 35914624 · DOI 10.1016/j.neubiorev.2022.104800
Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment.
Johnston JN, Kadriu B, Allen J, Gilbert JR, et al · · 2023 · cited 42× · PMID 36646310 · DOI 10.1016/j.neuropharm.2023.109422
Effect of naltrexone pretreatment on ketamine-induced glutamatergic activity and symptoms of depression: a randomized crossover study.
Jelen LA, Lythgoe DJ, Stone JM, Young AH, et al · · 2025 · cited 10× · PMID 40707608 · DOI 10.1038/s41591-025-03800-w
Regional blood flow signatures of opioidergic modulation of ketamine in major depressive disorder: a randomised crossover study
Jelen LA, O’Daly O, Zelaya FO, Stone JM, et al · · 2025 · DOI 10.1101/2025.08.18.25333599

Verify or expand the search:

Other trials of Naltrexone

Trials testing the same drug.

NCT07433413 — Evaluate the Efficacy and Safety of Naltrexone Hydrochloride Implant in Patients With Alcohol Use Disorder · Phase 3 · not yet recruiting
NCT06622239 — Trial to Evaluate the Effects of Naltrexone in Nonsuicidal Self-injury · Phase 2 · not yet recruiting
NCT06426303 — Sex Differences in Trauma, Inflammation and Brain Function and the Implications for Treatment Efficacy in Alcohol Use Di · Phase 4 · recruiting
NCT05968690 — Naltrexone and Propranolol Combined With Immunotherapy · Phase 1 · recruiting
NCT05458609 — Lemborexant Augmentation of Naltrexone for Alcohol Craving and Sleep · Phase 3 · completed

Other recruiting trials for Depressive Disorder, Treatment-Resistant

Currently open trials in the same condition.

NCT07053345 — A Study of Esketamine Nasal Spray in Korean Participants With Treatment-resistant Depression · Phase 4 · recruiting
NCT06668571 — Intravenous Ketamine for Treatment-Resistant Depression · Phase 2 · recruiting
NCT06511908 — Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resi · Phase 2 · recruiting
NCT05570344 — rTMS With and Without Text4Support for the Treatment of Resistant Depression. · NA · recruiting
NCT05641623 — OSU6162 as add-on in SSRI/SNRI-resistant Depression · Phase 2 · recruiting

Other King's College London trials

Trials by the same sponsor.

NCT07357064 — Professional Decision Making in Childbirth. · not yet recruiting
NCT07341087 — Skin Inflammation in Perimenopause: A Probiotic Intervention Proof of Concept Trial · NA · recruiting
NCT07228962 — Cutaneous Biomarkers in Atopic Eczema Using a Non-Invasive Micro-Suction Device in Babies · not yet recruiting
NCT07365722 — Comparison of Two Non-surgical Procedure to Manage Gum Disease Around Implants. · NA · not yet recruiting
NCT07378488 — Dance/Movement Therapy for Functional Neurological Disorder · NA · recruiting

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT04977674 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by King's College London
Last refreshed: 2 March 2023

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04977674.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing