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Clinical Trial
. 2024 Jun 6;24(1):190.
doi: 10.1186/s12883-024-03683-3.

Blocking CCR5 activity by maraviroc augmentation in post-stroke depression: a proof-of-concept clinical trial

Oren Tene  1   2 , Jeremy Molad  3 , Ofer Rotschild  3 , Aviva Alpernas  3 , Muhamad Hawwari  3 , Estelle Seyman  4 , Nir Giladi  5   6   7 , Hen Hallevi #  3   6   7 , Einor Ben Assayag #  8   9   10
Affiliations
Clinical Trial

Blocking CCR5 activity by maraviroc augmentation in post-stroke depression: a proof-of-concept clinical trial

Oren Tene et al. BMC Neurol. .

Abstract

Background: Post-stroke depression (PSD) is a significant impediment to successful rehabilitation and recovery after a stroke. Current therapeutic options are limited, leaving an unmet demand for specific and effective therapeutic options. Our objective was to investigate the safety of Maraviroc, a CCR5 antagonist, as a possible mechanism-based add-on therapeutic option for PSD in an open-label proof-of-concept clinical trial.

Methods: We conducted a 10-week clinical trial in which ten patients with subcortical and cortical stroke, suffering from PSD. were administered a daily oral dose of 300 mg Maraviroc. Participants were then monitored for an additional eight weeks. The primary outcome measure was serious treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. The secondary outcome measure was a change in the Montgomery-Asberg Depression Rating Scale (MADRS).

Results: Maraviroc was well tolerated, with no reports of serious adverse events or discontinuations due to intolerance. The MADRS scores substantially reduced from baseline to week 10 (mean change: -16.4 ± 9.3; p < 0.001). By the conclusion of the treatment phase, a favorable response was observed in five patients, with four achieving remission. The time to response was relatively short, approximately three weeks. After the cessation of treatment, MADRS scores increased at week 18 by 6.1 ± 9.6 points (p = 0.014).

Conclusions: Our proof-of-concept study suggests that a daily dosage of 300 mg of Maraviroc may represent a well-tolerated and potentially effective pharmacological approach to treating PSD. Further comprehensive placebo-controlled studies are needed to assess the impact of Maraviroc augmentation on PSD.

Trial registration: ClinicalTrials.gov Identifier: NCT05932550, Retrospectively registered: 28/06/2023.

Keywords: CCR5 antagonist; Clinical trial; Drug repurposing; Maraviroc; Post-stroke depression (PSD).

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Conflict of interest statement

Drs Ben Assayag, Tene, Hallevi and the Tel-Aviv Sourasky Medical Center have a pending patent application filed #62/978,324. No other disclosures were reported.

Figures

Fig. 1
Fig. 1
(A) Montgomery-Asberg Depression Rating Scale (MADRS) scores of the patients included in the study. B Mean difference in Montgomery-Asberg Depression Rating Scale (MADRS) scores over ten weeks of open treatment with Maraviroc versus eight weeks of follow-up. C 16-item quick inventory of depressive symptoms- self-report (QIDS-SR16) scores of the patients included in the study. D Clinical global impression (CGI) scores of the patients included in the study. E GAD-7 scores of the patients included in the study
Fig. 2
Fig. 2
Mean cognitive scores of patients included at baseline and after ten weeks of treatment with Maraviroc
See this image and copyright information in PMC

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