Dexamethasone for Excessive Menstruation

NCT01769820 | Completed Phase 2 DMC

• 1 other identifier: dexfemv2
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heavy Menstrual Bleeding

Keywords

Heavy menstrual bleeding (HMB); Dexamethasone; glucocorticoid

Outcome Measures

Primary Outcomes (1)

• Change or difference in mean laboratory measured menstrual blood loss(MBL)

  study1:Change in mean MBL between baseline and Dexamethasone treatment cycles. Study2:Difference in mean MBL between placebo and Dexamethasone treatment cycles. Study3 (adaptive):Change in mean MBL between baseline and cycles during randomised (Dexamethasone/placebo) treatment

  3-4months

Secondary Outcomes (5)

• Menstrual diary score for volume of menstrual period

  3-4months

• Satisfaction with treatment by means of a participant completed treatment review questionnaire

  3-4months

• Number of participants with adverse events as a measure of safety and tolerability

  3-4months

• Examine effect of treatment on Period pain via participant self-report questionnaire

  3-4months

• Mechanistic examination of response to Dexamethasone

  2 months

Study Arms (2)

Dexamethasone

ACTIVE COMPARATOR

Study 1, and study2(2 arms); Dexamethasone 1.5mg daily Study 3 (adaptive -7 arms): Dexamethasone of 0.4, 0.8, 1.0, 1.2, 1.5, and 1.8 mg total dose per day

Drug: Dexamethasone

Placebo

PLACEBO COMPARATOR

Placebo

Drug: placebo

Interventions

Dexamethasone DRUG

studies 1\&2:0.75mg twice daily for 5 days, starting on day LH (Luteinising Hormone)+8 of menstrual cycle; Study 3 (adaptive) 0.2,0.4,0.5,0.75,0.8,0.9mg twice daily as above

Also known as: D07AB19

Dexamethasone

placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (1)

University of Edinburgh

Edinburgh, EH16 4TJ, United Kingdom

Location

Related Publications (4)

• Critchley HO, Maybin JA. Molecular and cellular causes of abnormal uterine bleeding of endometrial origin. Semin Reprod Med. 2011 Sep;29(5):400-9. doi: 10.1055/s-0031-1287664. Epub 2011 Nov 7.

  PMID: 22065326 BACKGROUND

• Rae M, Mohamad A, Price D, Hadoke PW, Walker BR, Mason JI, Hillier SG, Critchley HO. Cortisol inactivation by 11beta-hydroxysteroid dehydrogenase-2 may enhance endometrial angiogenesis via reduced thrombospondin-1 in heavy menstruation. J Clin Endocrinol Metab. 2009 Apr;94(4):1443-50. doi: 10.1210/jc.2008-1879. Epub 2009 Jan 21.

  PMID: 19158196 BACKGROUND

• Warner P, Whitaker LHR, Parker RA, Weir CJ, Douglas A, Hansen CH, Madhra M, Hillier SG, Saunders PTK, Iredale JP, Semple S, Slayden OD, Walker BR, Critchley HOD. Low dose dexamethasone as treatment for women with heavy menstrual bleeding: A response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM). EBioMedicine. 2021 Jul;69:103434. doi: 10.1016/j.ebiom.2021.103434. Epub 2021 Jul 2.

  PMID: 34218053 DERIVED

• Warner P, Weir CJ, Hansen CH, Douglas A, Madhra M, Hillier SG, Saunders PT, Iredale JP, Semple S, Walker BR, Critchley HO. Low-dose dexamethasone as a treatment for women with heavy menstrual bleeding: protocol for response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM). BMJ Open. 2015 Jan 14;5(1):e006837. doi: 10.1136/bmjopen-2014-006837.

  PMID: 25588784 DERIVED

MeSH Terms

Conditions

Menorrhagia

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Uterine Hemorrhage; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Menstruation Disturbances

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Hilary Critchley, MBChB MD

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Reproductive Medicine

Study Record Dates

• First Submitted: December 19, 2012
• First Posted: January 17, 2013
• Study Start: January 1, 2013
• Primary Completion: March 29, 2018
• Study Completion: April 18, 2018
• Last Updated: October 25, 2018

Record last verified: 2018-10

Locations

GB (1)