H W Leow1, M Koscielniak1, L Williams2, P T K Saunders3, J Daniels4, A M Doust1, M-C Jones5, G D Ferguson6, Y Bagger6, A W Horne7, L H R Whitaker1. 1. MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. 2. Usher Institute, NINE Edinburgh BioQuarter, 9 Little France Road, Edinburgh, EH16 4UX, UK. 3. Centre for Inflammation Research, Queen's Medical Research Institue, University of Edinburgh, Edinburgh, EH16 4TJ, UK. 4. Clinical Trials Unit, University of Nottingham, University Park, Nottingham, NG7 2RD, UK. 5. Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. 6. Reproductive Medicine and Maternal Health, Ferring Research Institute, San Diego, CA, 92121, USA. 7. MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. Andrew.horne@ed.ac.uk.
Abstract
BACKGROUND: Endometriosis (where endometrial-like tissue is found outside the uterus) affects ~ 176 million women worldwide and can lead to debilitating pelvic pain. There is an unmet need for new medical treatment options for endometriosis. Pelvic peritoneal mesothelial cells of women with endometriosis exhibit detrimental metabolic reprogramming that creates an environment favouring the formation and survival of endometriosis lesions. We have generated powerful preclinical proof-of-concept data to show that it is possible to correct this metabolic phenotype using dichloroacetate (DCA), a non-hormonal compound previously used to treat rare metabolic disorders in children. We plan a single-arm, open-label, single site exploratory clinical trial to inform the design of a future randomised controlled trial (RCT) to determine the efficacy of DCA for the treatment of endometriosis-associated pain. METHODS: We will recruit 30 women with endometriosis-associated pain over a 6-month period. All participants will receive approximately 6.25 mg/kg oral DCA capsules twice daily for 6 weeks, with a dose increase to approximately 12.5 mg/kg twice daily for a further 6 weeks if their pain has not been adequately controlled on this dose regime and side-effects are acceptable. If pain is adequately controlled with minimal side-effects, the lower dose will be continued for a further 6 weeks. The primary objective is to determine whether it is possible to achieve acceptable recruitment and retention rates within the defined exclusion and inclusion criteria. Secondary objectives are to determine the acceptability of the trial to participants, including the proposed methods of recruitment, treatment, follow-up frequency and number of questionnaires. The recruitment rate will be determined by the proportion of patients recruited from the pool of eligible women. The retention rate will be determined by the proportion of participants who attended the final trial visit. DISCUSSION: This is a feasibility study to explore effectiveness and acceptability of the proposed field methodology (recruitment, retention, study processes and compliance with treatment). The results will be used to inform the design of a future RCT. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04046081 Registered 6 August 2019.
BACKGROUND: Endometriosis (where endometrial-like tissue is found outside the uterus) affects ~ 176 million women worldwide and can lead to debilitating pelvic pain. There is an unmet need for new medical treatment options for endometriosis. Pelvic peritoneal mesothelial cells of women with endometriosis exhibit detrimental metabolic reprogramming that creates an environment favouring the formation and survival of endometriosis lesions. We have generated powerful preclinical proof-of-concept data to show that it is possible to correct this metabolic phenotype using dichloroacetate (DCA), a non-hormonal compound previously used to treat rare metabolic disorders in children. We plan a single-arm, open-label, single site exploratory clinical trial to inform the design of a future randomised controlled trial (RCT) to determine the efficacy of DCA for the treatment of endometriosis-associated pain. METHODS: We will recruit 30 women with endometriosis-associated pain over a 6-month period. All participants will receive approximately 6.25 mg/kg oral DCA capsules twice daily for 6 weeks, with a dose increase to approximately 12.5 mg/kg twice daily for a further 6 weeks if their pain has not been adequately controlled on this dose regime and side-effects are acceptable. If pain is adequately controlled with minimal side-effects, the lower dose will be continued for a further 6 weeks. The primary objective is to determine whether it is possible to achieve acceptable recruitment and retention rates within the defined exclusion and inclusion criteria. Secondary objectives are to determine the acceptability of the trial to participants, including the proposed methods of recruitment, treatment, follow-up frequency and number of questionnaires. The recruitment rate will be determined by the proportion of patients recruited from the pool of eligible women. The retention rate will be determined by the proportion of participants who attended the final trial visit. DISCUSSION: This is a feasibility study to explore effectiveness and acceptability of the proposed field methodology (recruitment, retention, study processes and compliance with treatment). The results will be used to inform the design of a future RCT. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04046081 Registered 6 August 2019.
Authors: E D Michelakis; G Sutendra; P Dromparis; L Webster; A Haromy; E Niven; C Maguire; T-L Gammer; J R Mackey; D Fulton; B Abdulkarim; M S McMurtry; K C Petruk Journal: Sci Transl Med Date: 2010-05-12 Impact factor: 17.956
Authors: Steven Simoens; Gerard Dunselman; Carmen Dirksen; Lone Hummelshoj; Attila Bokor; Iris Brandes; Valentin Brodszky; Michel Canis; Giorgio Lorenzo Colombo; Thomas DeLeire; Tommaso Falcone; Barbara Graham; Gülden Halis; Andrew Horne; Omar Kanj; Jens Jørgen Kjer; Jens Kristensen; Dan Lebovic; Michael Mueller; Paola Vigano; Marcel Wullschleger; Thomas D'Hooghe Journal: Hum Reprod Date: 2012-03-14 Impact factor: 6.918