Dexamethasone for Excessive Menstruation

• Status: Completed
• Trial end date: 2018-04-18
• Target enrollment: 0
• Participant gender: Female

Summary

This study builds on previous research which has provided compelling evidence that deficient activity of glucocorticoids in the endometrium is a cause of increased menstrual bleeding. This study aims to demonstrate that a glucocorticoid (dexamethasone), already in common use for other conditions, (eg to treat medical conditions such as asthma and rheumatoid arthritis in early pregnancy), will reverse the endometrial glucocorticoid deficiency and as a result reduce menstrual blood loss.

The study is in two stages, a 12 month workup stage and a 3 year, response adaptive, dose-finding randomised controlled trial. The first stage involves two workup clinical studies to gather preliminary safety and efficacy data from first-in-Heavy Menstrual Bleeding use of oral dexamethasone. They will also provide methodological data for a series of simulation studies to determine a robust adaptive trial design specification.

Workup study 1: is unblinded, six patients will be given Dexamethasone (0.75mg twice daily) for 5 days during two consecutive menstrual cycles and will have an endometrial biopsy and MRI on two occasions (in a nontreated cycle, and the second of the cycles treated with Dexamethasone). Workup study 2; is a doubleblind crossover trial of 14 women -2 treatment blocks of two cycles each, with either placebo or Dexamethasone (0.75mg twice daily), randomised to order of treatments blocks - placebo then Dexamethasone, or vice-versa.

Adaptive trial: 54 month double-blind, placebo controlled trial of 108 women to evaluate the effect of Dexamethasone across a range of doses with the aim of identifying the optimal dose to be studied in a subsequent Phase III trial.

Participants will be randomised to receive one of 6 active doses or placebo over 3 menstrual cycles.

All studies will involve asking participants to complete menstrual diaries and to carry out menstrual blood loss collections to objectively measure blood loss.

The investigators' proposed approach is novel use of synthetic glucocorticoid to "rescue" luteal phase deficiency of cortisol, and thus improve endometrial vasculature and hence vasoconstriction when menses commences, and thus reduce menstrual bleeding.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Edinburgh
• Collaborator: NHS Lothian
• Treatments: BB 1101; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Glucocorticoids

Criteria

Inclusion Criteria:

• Complaint of HMB, including women with fibroids

• Pre-menopausal

• Age 18 years and over

• Describing menstrual cycles every 21- 42 days

• Provide written informed consent prior to any study related procedures

• If of childbearing potential either agree to practice a non-hormonal method of contraception for duration of study or have a partner with a vasectomy

• Workup (Study 1 or 2)- MBL for single screening period is >= 50mL

• Adaptive Trial (Study 3)- average MBL for two screening menstrual collections is >= 50mL

Exclusion Criteria:

• Currently breast-feeding

• History or current uterus, cervix, ovarian or breast cancer

• Known severe coagulation disorder

• Glucocorticoid treatment or sex steroid administration by any route in previous 1 month

• Taking prohibited medication -

• Thyroid, renal or liver dysfunction

• Diabetes mellitus

• Treated moderate/severe hypertension

• Psychotic depressive illness

• Rare hereditary galactose intolerance, lactase deficiency or glucose galactose malabsorption (due to lactose content of trial medication)

• Has a problem with alcohol or drug abuse

• Has a mental condition rendering her unable to understand the nature and scope of the study

• Participation in treatment phase in any earlier DexFEM study (1 or 2)

• Is currently enrolled in an investigational drug or device study or participated in such a study within the previous 30 days and is still in exclusion period

• workup study 1, only, an additional exclusion criterion of any contra-indication to MRI