Cancer prevention Cancer
Conditions
Interventions
Women will either be approached in clinics or by invitation through mailshot from the Nightingale Family History clinic. Posters will also be placed in clinics and staff invited to join if they fulfil
Sponsors
Manchester University NHS Foundation Trust
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Women aged 30-50 years 2. BMI =30 kg/m2 or =27.5 mg/m2 in Asian and South Asian women 3. Pre-menopausal, with regular menstrual cycles (cycle length 21 to 40 days) 4. Have access to and be able to use a smartphone or tablet running iOS or Android and be able to use the Oviva app OR access and ability to use a telephone 5. Willing to follow the TDR using Optifast® drinks and have previously sampled them 6. Agree to maintain non-hormonal contraception (barrier or abstinence) until both sets of biopsies are complete and must have a negative urine pregnancy test at screening. 7. Women with Type 2 Diabetes Mellitus on diet +/- Metformin control can be included. 8. Must be able to read, understand and communicate in English
Exclusion criteria
Exclusion criteria: 1. Prior history of breast or endometrial cancer or preinvasive breast disease (Ductal Carcinoma in situ (DCiS), Lobular Carcinoma in situ (LCiS), Atypical Ductal Hyperplasia (ADH), Atypical Lobular Hyperplasia (ALH)) 2. Any hormonal contraceptive (including progestin releasing IUCD, such as Mirena®) in the 12 weeks prior to study entry 3. Preventative Tamoxifen therapy within the last 6 months 4. Prior anti-progestin therapy (e.g. Ulipristal Acetate) within the last 6 months 5. Carrier of the BRCA 1 or 2 gene 6. Confirmed pregnant via a pregnancy test at screening, planning pregnancy in the next 12 months, or currently breast feeding 7. Taking prohibited medications (see Appendix 1) including warfarin or novel anticoagulants (NOAC), low molecular weight heparin (LMWH) or equivalent anti-coagulants, anti-psychotic medication, anti-diabetic medication other than Metformin 8. Currently on treatment with Orlistat or other pharmacological treatments for weight loss 9. Chronic use of steroids (more than 20mg daily of prednisolone or its equivalent) 10. Previously had bariatric surgery for weight loss including gastric bypass and sleeve gastrectomy 11. Hypersensitivity to any of the ingredients of Optifast® e.g. lactose intolerance 12. Allergies to the ingredients of Optifast® e.g. fish, milk, soy 13. Substance abuse or harmful alcohol use as indicated by a score of 16 or above on the Alcohol Use Disorders Identification Test (AUDIT) 14. Diagnosed with an eating disorder, or patients with severe binge eating assessed by a score of 27 or more on the Binge Eating Scale (BES) 15. Severe depression assessed by a score of 15 or more on the Patient Health Questionnaire-9 (PHQ-9) questionnaire. 16. Severe anxiety assessed by a score of 15 or more on the General Anxiety Disorder (GAD-7) questionnaire. 17. Psychiatric or physical comorbidity or scheduled for major surgery, which in the opinion of the treating medical physician, or the Chief Investigator (CI), would compromise their safety or adherence to the study 18. Lack capacity or are unable to read or understand written or verbal instructions in English
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Epithelial cell proliferation (Ki67) in the breast and endometrium at baseline and 12 +/- 4 weeks measured using biopsy | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Cancer risk biomarkers; including fasting insulin, lipids, glucose, inflammatory markers inc. CRP, leptin, adiponectin, methylation, insulin like growth factor -1 (IGF-1) measured using blood tests at baseline, 3, 6, 9, and 12 months 2. Uptake, retention and adherence to TDR and 12-month weight loss programme measured using patient records at end of study 3. Weight (kg) measured at baseline, 3, 6, 9, and 12 months 4. Body fat measured using bioelectrical impedance at baseline, 3, 6, 9, and 12 months 5. Fat free mass (kg) measured using bioelectrical impedance at baseline, 3, 6, 9, and 12 months 6. Waist and hip circumference measured at baseline, 3, 6, 9, and 12 months 7. Blood and tissue markers of breast and endometrial cancer and cardiovascular disease measured using a blood test and biopsy at baseline, 3, 6, 9, and 12 months 8. Quality of life (anxiety, depression, quality of life, self-efficacy, self-satisfaction with weight loss during the programme measured using: Generalised Anxiety Disorder-7 [GAD-7] scale, Participant Health Questionnaire-9 [PHQ-9], EQ-5D-3L, Weight Efficacy Lifestyle Questionnaire Short Form [WEL-SF], Obesity and Weight Loss Quality of Life [OWL-QOL] baseline, 3 months, 6 months, 9 months, 12 months, 15 months (control group only) 9. Adverse effects measured using patient records at end of study 10. Diet measured using a 7 day food diary questionnaire at baseline, 3 months, 6 months, 9 months, 12 months, 15 months (control group only) 11. Physical activity behaviours measured using IPAQ at baseline, 3 months, 6 months, 9 months, 12 months, 15 months (control group only) 12. Fidelity of delivery of the 12-month TDR and weight loss programme measured using adherence (7 day food diary)/compliance (weight loss) /loss to follow-up - evaluated at close of trial Exploratory outcome measures: 13. Markers of the cellular hierarchy in breast +/- endometrium measured using dual immunofluorescence/FACS sorting, using paired biopsy samples from | — |
Countries
England, United Kingdom
Contacts
Public ContactSacha;Emma Howell;Crosbie
;
Outcome results
None listed