Effect of 17ß-estradiol on Inflammatory-immune Responses in Post-menopausal Women According to Administration Route

May 10, 2017 updated by: University Hospital, Toulouse

Effect of 17ß-estradiol on Inflammatory-immune Responses in Post-menopausal Women According to Administration Route: Pilot Study

The aim of this pilot study conducted in post-menopausal women is to evaluate the effect of 17ß-estradiol administration on inflammatory-immune cells, namely antigen-presenting cells (monocytes/dendritic cells), and more precisely on their activation by inflammatory stimuli. This study will allow us to determine our ability to recruit menopausal women and to characterize the optimal primary end-point among the numerous criteria tested

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Although the beneficial effects of hormonal replacement therapy (HRT) against osteoporosis and climacteric symptoms have been clearly established, randomized studies recently revealed that the combined administration of oral estrogens and medroxyprogesterone acetate increases the incidence of coronary events and strokes during the first months of treatment. Furthermore, oral estrogens significantly enhance IL-6 and CRP secretion. This increase in the plasma concentration of inflammatory markers probably results from a direct effect of oral administration on the liver, since i twas not observed with estrogens administered by transdermal route.

Our experimental data in ovariectomized mice demonstrated that the chronic subcutaneous administration of17ß-estradiol (E2) enhances the expression of pro-inflammatory cytokines by Th1 lymphocytes, Natural Killer T cells and monocytes/macrophages. This pro-inflammatory effect of E2 could play a role in the deleterious vascular effects observed in randomized studies, especially by favoring plaque instability.

Our aim is to determine whether E2 administration in menopausal women leads to an inflammatory phenotype of circulating antigen-presenting cells, especially monocytes. Indeed, evaluating the inflammatory status at the cellular level probably gives more precise informations than plasma cytokine concentrations to predict the ability of estrogens to enhance inflammatory processes. We first propose a pilot study in order to determine enrollment feasibility, as well as the optimal biological endpoints to assess monocyte activation status. These latter criteria will be then used in a future randomized study comparing two routes of E2 administration (oral vs transdermal).

The present study will include 34 menopausal women. After the inclusion visit, three visits will be performed with the collection of a 50 ml blood sample and the isolation of circulating immune cells (monocytes).

The following criteria will be studied before (V1 and V2) and after 30 ± 3 days of E2 treatment (V3:

  1. expression of surface activation molecules.
  2. Secretion of cytokines in response to several Toll-like receptor stimuli.
  3. IL-6 and CRP-US plasma concentrations.

We will first assess the intra-individual variability (V1 and V2). At visit 2 (V2), the subjects will be randomized to receive E2 either by oral (n= 17) or transdermal (n= 17) route.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Toulouse, France, 31059
        • University Hospital Toulouse

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Women with confirmed menopause (duration : 1 to 5 years)
  • No contra-indication of hormonal replacement therapy due to medical history
  • Mammogram without significant abnormality (< 12 months)
  • Normal body mass index (BMI) (19 ≤ IMC ≤ 25 kg/m2)
  • No treatment with estrogens and/or progestatives and/or SERM (specific moduator of estrogen receptor) and/or phytoestrogènes ongoing or stopped for less than 3 months
  • No clinical or biological abnormality or treatment indicating the presence of an infectious or inflammatory disease.
  • No participation to another clinical study during the 3 months before the inclusion
  • Ability to sign the consent form.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1 Oral
oestradiol by oral administration - Estrofem 2 mg
Drug: oestradiol
oestradiol 2 mg oral route 30 days
Other Names:
  • Estrofem
Drug: oestradiol
oestradio transdermal patch 60ug by 24 hours 30 days
Other Names:
  • Oestrapatch
Experimental: 2 patch
oestradiol par patch - Estrapatch 60microg/24h
Drug: oestradiol
oestradiol 2 mg oral route 30 days
Other Names:
  • Estrofem
Drug: oestradiol
oestradio transdermal patch 60ug by 24 hours 30 days
Other Names:
  • Oestrapatch

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine the feasibility of a future multicentric randomized trial : estimation of the number of subjects required
Time Frame: 1 month
1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
variability and repeatability of the biological parameters studied
Time Frame: 1 month
number of circulating immune cells, expression of surface molecules by monocytes, secretion of cytokines following TLR activation
1 month
Feasibility of the recruitment, enrollment and follow-up of menopausal women
Time Frame: End of study
End of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Toulouse

Investigators

  • Principal Investigator: Pierre GOURDY, Hospital University Toulouse

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

February 22, 2007

First Submitted That Met QC Criteria

June 18, 2008

First Posted (Estimate)

June 19, 2008

Study Record Updates

Last Update Posted (Actual)

May 11, 2017

Last Update Submitted That Met QC Criteria

May 10, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0507402

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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