Effect of 17ß-Estradiol on Inflammatory-Immune Responses in Post-Menopausal Women According to Administration Route
Information source: University Hospital, Toulouse
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Postmenopausal
Intervention: oestradiol (Drug); oestradiol (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: University Hospital, Toulouse Official(s) and/or principal investigator(s):
Pierre GOURDY, Principal Investigator, Affiliation: Hospital University Toulouse
Overall contact:
Pierre GOURDY, MD, Phone: 33-56-132-2685, Email: gourdy.p@chu-toulouse.fr
Summary
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
Clinical Details
Official title: Effect of 17ß-Estradiol on Inflammatory-Immune Responses in Post-Menopausal Women According to Administration Route: Pilot Study
Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Pharmacodynamics Study
Primary outcome: To determine the feasibility of a future multicentric randomized trial : estimation of the number of subjects required
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.
Eligibility
Minimum age: 45 Years.
Maximum age: 60 Years.
Gender(s): Female.
Criteria:
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.
Locations and Contacts
Pierre GOURDY, MD, Phone: 33-56-132-2685, Email: gourdy.p@chu-toulouse.fr
University Hospital Toulouse, Toulouse 31059, France; Recruiting
Claude RIBOT, MD
Florence TREMOLLIERES, MD, Sub-Investigator
Claude RIBOT, MD, Sub-Investigator
Additional Information
Starting date: September 2006
Ending date: November 2009
Last updated: June 18, 2008
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