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Impact of sitagliptin on endometrial mesenchymal stem-like progenitor cells : a randomised, double-blind placebo-controlled feasibility trial
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Tewary, Shreeya, Lucas, Emma S., Fujihara, Risa, Kimani, Peter K., Polanco, Angela, Brighton, Paul (Paul J.), Muter, Joanne, Fishwick, Katherine, Da Costa, Maria José Minhoto Diniz, Ewington, Lauren J., Lacey, Lauren, Takeda, Satoru, Brosens, Jan J. and Quenby, Siobhan (2020) Impact of sitagliptin on endometrial mesenchymal stem-like progenitor cells : a randomised, double-blind placebo-controlled feasibility trial. EBioMedicine, 51 . 102597. doi:10.1016/j.ebiom.2019.102597 ISSN 2352-3964.
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Official URL: http://dx.doi.org/10.1016/j.ebiom.2019.102597
Abstract
Background:
Recurrent pregnancy loss (RPL) is associated with the loss of endometrial mesenchymal stem-like progenitor cells (eMSC). DPP4 inhibitors may increase homing and engraftment of bone marrow-derived cells to sites of tissue injury. Here, we evaluated the effect of the DPP4 inhibitor sitagliptin on eMSC in women with RPL, determined the impact on endometrial decidualization, and assessed the feasibility of a full-scale clinical trial.
Methods:
A double-blind, randomised, placebo-controlled feasibility trial on women aged 18 to 42 years with a history of 3 or more miscarriages, regular menstrual cycles, and no contraindications to sitagliptin. Thirty-eight subjects were randomised to either 100 mg sitagliptin daily for 3 consecutive cycles or identical placebo capsules. Computer generated, permuted block randomisation was used to allocate treatment packs. Colony forming unit (CFU) assays were used to quantify eMSC in midluteal endometrial biopsies. The primary outcome measure was CFU counts. Secondary outcome measures were endometrial thickness, study acceptability, and first pregnancy outcome within 12 months following the study. Tissue samples were subjected to explorative investigations.
Findings:
CFU counts following sitagliptin were higher compared to placebo only when adjusted for baseline CFU counts and age (RR: 1.52, 95% CI: 1.32–1.75, P<0.01). The change in CFU count was 1.68 in the sitagliptin group and 1.08 in the placebo group. Trial recruitment, acceptability, and drug compliance were high. There were no serious adverse events. Explorative investigations showed that sitagliptin inhibits the expression of DIO2, a marker gene of senescent decidual cells.
Interpretation:
Sitagliptin increases eMSCs and decreases decidual senescence. A large-scale clinical trial evaluating the impact of preconception sitagliptin treatment on pregnancy outcome in RPL is feasible and warranted.
Funding:
Tommy's Baby Charity.
Clinical trial registration:
EU Clinical Trials Register no. 2016-001120-54.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology R Medicine > R Medicine (General) R Medicine > RG Gynecology and obstetrics |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Pregnancy -- Complications -- Research, Miscarriage -- Research, Endometrium, Stem cells, Decidua, Clinical trials | ||||||||||||
| Journal or Publication Title: | EBioMedicine | ||||||||||||
| Publisher: | Elsevier BV | ||||||||||||
| ISSN: | 2352-3964 | ||||||||||||
| Official Date: | 9 January 2020 | ||||||||||||
| Dates: |
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| Volume: | 51 | ||||||||||||
| Article Number: | 102597 | ||||||||||||
| DOI: | 10.1016/j.ebiom.2019.102597 | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||
| Date of first compliant deposit: | 10 January 2020 | ||||||||||||
| Date of first compliant Open Access: | 20 January 2020 | ||||||||||||
| RIOXX Funder/Project Grant: |
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