Specialty: Metabolic and endocrine disorders, Primary sub-specialty: Metabolic and endocrine disorders
Conditions
Interventions
DOMINO is a prospective double-blinded randomised controlled trial comparing the Fractyl Revita duodenal mucosal resurfacing device to a sham procedure in women with PCOS to ascertain its effect on in
Sponsors
Imperial College of Science, Technology and Medicine
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Female participants 2. Age 18-45 3. Body mass index (BMI) = 30 kg/m2 4. Diagnosis of PCOS based on the NIH Criteria. Require ALL of the following: 4.1. Menstrual irregularity (anovulation or >35 day cycle) 4.2. Clinical or biochemical hyperandrogenism 4.3. Exclusion of other causes other aetiologies of menstrual dysfunction (e.g. thyroid dysfunction, hyperprolactinaemia) 5. Insulin resistance as defined by a 2-hour oral glucose tolerance test glucose concentration of 7.8 mmol/l and/or HOMA-IR = 3.0. 6. Willing to comply with study requirements and able to give informed consent
Exclusion criteria
Exclusion criteria: 1. Type 1 or Type 2 diabetes mellitus 2. History of any medical, psychological or other condition, or use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or potentially cause harm to the volunteer. These includes: 2.1. Active H. pylori infection (Participants with active H. pylori may continue with the screening process if they are treated via medication and re-testing verifies the condition has resolved.) 2.2. Previous gastrointestinal surgery that could affect the ability to treat the duodenum such as subjects who have had a Billroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions 2.3. History of chronic or acute pancreatitis 2.4. Known active hepatitis or active liver disease 2.5. Symptomatic gallstones or kidney stones, acute cholecystitis or history of duodenal inflammatory diseases including Crohn’s Disease and Celiac Disease 2.6. History of coagulopathy, upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia 2.7. Use of anticoagulation therapy (such as warfarin) which cannot be discontinued for 7 days before and 14 days after the procedure 2.8. Use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 14 days before and 14 days after the procedure. Use of aspirin is allowed. 2.9. Unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 4-weeks post procedure phase 2.10. Taking corticosteroids or drugs known to affect GI motility (e.g. Metoclopramide) 2.11. Persistent anaemia, defined as haemoglobin< 10 g/dl 2.12. eGFR < 30 ml/min/1.73m2 2.13. Active systemic infection 2.14. Active malignancy within the last 5 years 2.15. Poor candidates for surgery or general anaesthesia 2.16. Active illicit substance abuse or alcoholism 3. Medications affecting insulin sensitivity (oral steroids, metformin, thiazolidinediones, atypical antipsychotics, hormonal contraceptives, weight loss medication) at screening or 6 months previously. 4. Other causes of anovulation (e.g. hypothyroidism, adrenal or pituitary disorders) 5. More than 6 menstrual bleeds within the previous 12 months 6. Current pregnancy or breastfeeding at screening or 6 months previously 7. Smoking at screening or 6 months previously 8. Without access at home to a telephone or other factor likely to interfere with ability to participate reliably in the study 9. Donated blood during the preceding 3 months or intention to do so before the end of the study 10. Any other mental or physical condition which, in the opinion of the Investigator, makes the subject a poor candidate for clinical trial participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Reproductive outcomes are assessed as the number of ovulatory cycles over the study period defined by the increase in serum progesterone followed by menstrual bleeding. This will be assessed with: 1.1. Reproductive blood tests measured at baseline, once or twice weekly from weeks 12-24 post-procedure and 6-month clinical visit 1.2. Weekly pelvic ultrasound scan from weeks 12-24 post-procedure 2. Metabolic outcome are measured using hepatic and peripheral insulin sensitivity at baseline and at 12 weeks post procedure with: 2.1. Euglycaemic-hyperinsulinaemic clamp and 2.2. Oral glucose tolerance test. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Body weight is measured using a weighing scale at baseline, at the early post-procedure visit, at 12 weeks post-procedure and at 6-months 2. Body composition is measured using the Tanita machine at baseline, at the early post-procedure visit, at 12 weeks post-procedure and at 6-months 3. Post-prandial glucose, insulin and c-peptide excursions is measured using biochemical lab studies at the screening visit, baseline visit, early post-procedure visit, 12-week post-procedure visit 4. Reproductive hormone profile is measured using biochemical lab studies at the screening visit, baseline visit, early post-procedure visit, 12 week post-procedure visit, once / twice weekly visits from weeks 12-24 and the 6-month clinical visit 5. Ovarian follicle development is measured using weekly pelvic ultrasound scan from weeks 12-24 post-procedure 6. Liver function tests and lipid profile are measured using biochemical lab studies at the screening visit, baseline visit, early post-procedure visit, 12 week post-procedure visit, once / twice weekly visits from weeks 12-24 and the 6-month clinical visit 7. Number of medications and adverse events are recorded from the patient's history and clinical examination at every visit 8. Blood pressure readings are recorded clinically using a digital sphygmomanometer and assessed at every visit. Heart rate measurements are recorded with a finger probe and assessed at every visit | — |
Countries
United Kingdom
Contacts
Public ContactVasha Kaur
Outcome results
None listed