EPiC
Research type
Research Study
Full title
A single-arm open label exploratory clinical trial to evaluate dichloroacetate (DCA) as a possible treatment for endometriosis-associated pain: EPiC
IRAS ID
254863
Contact name
Andrew Horne
Contact email
Sponsor organisation
University of Edinburgh
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
REC reference number, 19/SS/0063
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Research Summary
Endometriosis is a chronic condition usually affecting women throughout their reproductive lives. It is defined as a growth of endometrial-like tissue (womb lining) outside the uterus (womb) and is associated with chronic pelvic pain that can be frequent and severe, resulting in tiredness, lower quality of life and difficulties in getting pregnant. Current treatments are unsatisfactory and there is an unmet need for new medical treatment for endometriosis.
Research findings from our laboratory have shown that women with endometriosis have more lactate in their pelvis. In laboratory models of endometriosis, we have tested dichloroacetate (DCA), a compound used to treat metabolic disorders in children. Our results showed that DCA could stop the growth and survival of endometriosis cells and reduce lactate production. In our study we plan to investigate if we can we can recruit and retain women into a trial using this treatment. We will recruit 30 women aged 18 or over, pelvic pain and diagnosis of endometriosis within the last three years. Participants will complete informed consent, be willing to comply with the treatment and use contraception throughout the trial. We will recruit patients over six months at Royal Infirmary of Edinburgh. Women who consent will take a daily dose of DCA capsules for 12 weeks. They will come to the hospital for five visits in total and will have one follow-up phone call after they finish the treatment. At each visit, participants will be asked about their general health/side effects, have blood samples taken and will complete questionnaires at three of those visits.
Moreover, we will recruit four healthy volunteers who will be asked to take DCA once (12.5mg/kg). We will collect their blood sample before and 30-60 min after the treatment, which will be used to calibrate laboratory equipment used to detect DCA.Summary of Results
Introduction There is an unmet need for new medical treatments for endometriosis. Pelvic peritoneal mesothelial cells of women with endometriosis exhibit detrimental metabolic reprogramming that favours formation/survival of endometriosis lesions. Our preclinical, proof-of-concept data demonstrates that it is possible to correct this metabolic phenotype using dichloroacetate (DCA), but this has not been evaluated in patients.
Aim
To determine feasibility of a clinical trial of DCA to treat endometriosis-associated pain Materials and Methods
Design: Single-arm, open-label, single-site exploratory study
Population: 30 women with surgically-confirmed ASRM stage I-II endometriosis
Intervention: oral DCA for 12 weeks (6.25mg/kg twice daily, increasing to 12.5mg/kg twice daily after six weeks depending on response) Primary outcome: Recruitment and retention Secondary outcomes: Compliance, side-effects and acceptability Results
93 patients were approached and 34/54 eligible patients were recruited. Retention met pre-specified criteria. Return of numerical rating scores of pain was 85% and completion of study assessments 90%. 70% of participants completed all 12 weeks of treatment and 95% reporting taking all, or almost all, of prescribed DCA. Side-effects were common but typically mild (only two participants consequently stopped treatment). 79% of participants described the trial as a positive experience. Whilst unpowered for efficacy, 79% of participants had a clinically meaningful reduction in pain scores, 62% reported using less analgesia, and mean Endometriosis Health Profile-30 score improved from 64.7 to 37.0.
Conclusions and impact
Recruitment and retention to clinical trials of DCA for endometriosis appear feasible. DCA is a promising treatment for endometriosis-associated pain but requires assessment in placebo-controlled trials.REC name
South East Scotland REC 01
REC reference
19/SS/0063
Date of REC Opinion
6 Jun 2019
REC opinion
Further Information Favourable Opinion