PostmenopausalPhase 4NCT00701337
Effect of 17ß-estradiol on Inflammatory-immune Responses in Post-menopausal Women According to Administration Route
A Phase 4 study testing oestradiol in people with Postmenopausal, run by University Hospital, Toulouse at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 to 60 years, women only
- Conditions the study is for
- Postmenopausal
- What is being tested?
- oestradiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2006to Jan 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 60 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Read the 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:
- expression of surface activation molecules.
- Secretion of cytokines in response to several Toll-like receptor stimuli.
- 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.
- Conditions
- Postmenopausal
- Being tested
- oestradiol
- Keywords
- Estrogen Replacement Therapy, menopausal women
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oestradiolDrug
Also called Estrofem
oestradiol 2 mg oral route 30 days
oestradiolDrug
Also called Oestrapatch
oestradio transdermal patch 60ug by 24 hours 30 days
| Study group | Role | What they receive |
|---|---|---|
| 1 Oral | Experimental | oestradiol by oral administration - Estrofem 2 mg Receives: Drug: oestradiol |
| 2 patch | Experimental | oestradiol par patch - Estrapatch 60microg/24h Receives: Drug: oestradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the feasibility of a future multicentric randomized trial : estimation of the number of subjects required
Measured: 1 month
Secondary outcomes (2)
variability and repeatability of the biological parameters studied
number of circulating immune cells, expression of surface molecules by monocytes, secretion of cytokines following TLR activation
Measured: 1 month
Feasibility of the recruitment, enrollment and follow-up of menopausal women
Measured: End of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2008 (estimated)
- Study startSep 2006
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PostmenopausalStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre GOURDY, Principal investigator, Hospital University Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00701337
- Sponsor's protocol ID
- 0507402
- Status last verified
- May 2017
- First submitted
- 22 Feb 2007
- Last updated
- 11 May 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Seillet C, Laffont S, Tremollieres F, Rouquie N, Ribot C, Arnal JF, Douin-Echinard V, Gourdy P, Guery JC. The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor alpha signaling. Blood. 2012 Jan 12;119(2):454-64. doi: 10.1182/blood-2011-08-371831. Epub 2011 Nov 16.
PubMed 22096248
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of 17ß-estradiol on Inflammatory-immune Responses in Post-menopausal Women According to Administration Route: Pilot Study
- ClinicalTrials.gov ID
- NCT00701337
- Acronym / sponsor ID
- 0507402
- Conditions
- Postmenopausal
- Keywords
- Estrogen Replacement Therapy, menopausal women
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- Sep 2006
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 19 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- expression of surface activation molecules.
- Secretion of cytokines in response to several Toll-like receptor stimuli.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 Oral | Experimental | Drug: oestradioloestradiol by oral administration - Estrofem 2 mg |
| 2 patch | Experimental | Drug: oestradioloestradiol par patch - Estrapatch 60microg/24h |
Who may qualify
- Ages
- 45 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| oestradiolAlso: Estrofemoestradiol 2 mg oral route 30 days | Drug | 1 Oral |
| oestradiolAlso: Oestrapatchoestradio transdermal patch 60ug by 24 hours 30 days | Drug | 2 patch |
Primary outcome
To determine the feasibility of a future multicentric randomized trial : estimation of the number of subjects required
Time frame: 1 month
2 secondary outcomes
variability and repeatability of the biological parameters studied
Time frame: 1 month
Feasibility of the recruitment, enrollment and follow-up of menopausal women
Time frame: End of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2017.
- Results publication: PubMed 22096248Seillet C, Laffont S, Tremollieres F, Rouquie N, Ribot C, Arnal JF, Douin-Echinard V, Gourdy P, Guery JC. The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor alpha signaling. Blood. 2012 Jan 12;119(2):454-64. doi: 10.1182/blood-2011-08-371831. Epub 2011 Nov 16.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre GOURDY principal investigator
Hospital University Toulouse
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing oestradiol in people with Postmenopausal, run by University Hospital, Toulouse at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the feasibility of a future multicentric randomized trial : estimation of the number of subjects required (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00701337, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2017.