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

This study has been completed.
Sponsor:
Information provided by:
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT00701337
First received: February 22, 2007
Last updated: June 29, 2010
Last verified: June 2010
  Purpose

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


Condition Intervention Phase
Postmenopausal
Drug: oestradiol
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of 17ß-estradiol on Inflammatory-immune Responses in Post-menopausal Women According to Administration Route: Pilot Study

Resource links provided by NLM:


Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • To determine the feasibility of a future multicentric randomized trial : estimation of the number of subjects required [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • variability and repeatability of the biological parameters studied [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    number of circulating immune cells, expression of surface molecules by monocytes, secretion of cytokines following TLR activation

  • Feasibility of the recruitment, enrollment and follow-up of menopausal women [ Time Frame: End of study ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: September 2006
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Oral
oestradiol by oral administration - Estrofem 2 mg
Drug: oestradiol
oestradiol 2 mg oral route 30 days
Other Name: Estrofem
Experimental: 2 patch
oestradiol par patch - Estrapatch 60microg/24h
Drug: oestradiol
oestradio transdermal patch 60ug by 24 hours 30 days
Other Name: Oestrapatch

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

Ages Eligible for Study:   45 Years to 60 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00701337

Locations
France
University Hospital Toulouse
Toulouse, France, 31059
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
Principal Investigator: Pierre GOURDY Hospital University Toulouse
  More Information

No publications provided

Responsible Party: LLAU Marie-Elise, University Hospital Toulouse
ClinicalTrials.gov Identifier: NCT00701337     History of Changes
Other Study ID Numbers: 0507402
Study First Received: February 22, 2007
Last Updated: June 29, 2010
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Toulouse:
Estrogen Replacement Therapy
menopausal women

Additional relevant MeSH terms:
Estradiol
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Estradiol valerate
Polyestradiol phosphate
Contraceptive Agents
Contraceptive Agents, Female
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014