Healthy Women Volunteers Clinical Trial
— MUCOVACOfficial title:
Study of Immunity at the Genital Mucosa of HIV-1 Infected and Healthy Women
Current knowledge on mucosa, especially genitals in women, however, remain inadequate,
especially regarding defense mechanisms and possibilities for a vaccine to induce an active
immune response at mucosal front door of the most pathogens. Induction of mucosal immune
response has emerged as a research priority research prophylactic vaccine.The development of
strategies to prevent sexual transmission of HIV-1 depends in part on an understanding of
specific and innate immune mechanisms involved in this transmission.
MUCOVAC is a feasibility study of the immunological and transcriptomic analysis of
cervicovaginal samples of women infected or not infected with HIV-1. We also assess
tolerance samples taken by cytobrush and cervicovaginal washings, efficiency and
reproducibility of the sample by cytobrush and cervicovaginal lavage for transcriptomic
analysis, measurement of cytokines by Luminex technology, quantification of IgG and IgA. In
blood we will determine the phenotype of B cells and Tfh cell frequency (T follicular
helper) and quantification of serum immunoglobulins and will perform a transcriptomic
analysis of blood cells. Finally we will make correlations with the observed responses at
the genital mucosa.
This pathophysiological exploratory study will be performed in 20 women infected with HIV-1
and 20 healthy women recruited from two centers in France and will include a screening visit
and two visits M0 and M1 during which mucous and blood samples will be performed.
The results of the study will capitalize skills in biology mucosa, using powerful tools to
assess mucosal immunological parameters.
| Status | Terminated |
| Enrollment | 14 |
| Est. completion date | January 2015 |
| Est. primary completion date | November 2014 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Female |
| Age group | 18 Years to 45 Years |
| Eligibility |
Inclusion Criteria: - Free, informed and signed consent - Person affiliated or beneficiary of a social security system or the Universal Health Coverage - Female - No menopausal, aged 18 to 45 years, - Under oral contraceptive or implant - Urine pregnancy test negative - HBsAg and HCV serology negative - Cervicovaginal smear normal older than one year, - Normal vaginal smear dated within one year For healthy women * HIV serology negative For infected women - HIV-1 infection checked by western-blot and/or the detection of HIV-RNA - CD4+ T cells >350/mm3 (several tests, since 6 months) - Viral load <40 copies/ml since 6 months - Treated with antiretroviral drugs since 6 months Exclusion Criteria: - Significant history of vaginal pathology (malignancy, prolapse) - Hysterectomy, conization - History of abnormal Pap smear in the previous year (ASC-US, AG-US and LSIL and high grade according to Bethesda). - Breakthrough bleeding; - Clinical symptoms suggestive of genital infection within 10 days prior to the examination of the study, - Antibiotic systemically within 10 days prior to the examination of the study, - Immunosuppressive or immunomodulatory treatment in the last six months and corticosteroids (> 20 mg / day for 5 days) in last 3 months - Presence of other sexually transmitted infection detected in samples at pre-inclusion visit and ongoing at V1 visit (Mycoplasma, Chlamydia, gonorrhea, Trichomonas, Candida albicans and Syphilis) - A person participating in another research including a period of exclusion still ongoing selection - Population called vulnerable (minors, persons under guardianship, or deprived of liberty by a judicial decision. |
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label
| Country | Name | City | State |
|---|---|---|---|
| France | Centre d'investigation clinique Cochin Pasteur (CIC1417) | Paris | |
| France | Service des maladies infectieuses et tropicales | Saint Etienne |
| Lead Sponsor | Collaborator |
|---|---|
| French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Acceptability, tolerance, Efficiency | Acceptability Local tolerance of sampling (particularly for collection by cytobrush), bleeding (need for protection, abundance, frequency) leucorrhoea (frequency, amount, aspect), fever, pain, gynecological vaginal burns and general tolerance (fever, occurrence of pelvic infection). Efficiency of collection by washing (Ig rate > 1µg/ml) and quality of cells collected by cytobrush and of cell pellet from washes for a transcriptomic analysis (the quantity and quality of RNA: RIN (RNA integrity number) > 5 and an amount of RNA 50> ng) |
2 months | Yes |
| Secondary | Concentration of antibodies in cervicovaginal samples | Concentration of antibodies in cervicovaginal samples | Month 0 and month 1 | No |
| Secondary | Concentration of cytokines in cervicovaginal samples | Concentration of cytokines in cervicovaginal samples | month 0 and month 1 | No |
| Secondary | Expression genomics in cervicovaginal specimens and whole blood | Expression genomics in cervicovaginal specimens and whole blood | month 0 and month 1 | No |
| Secondary | B phenotypes and the frequency of Tfh cells in whole blood | B phenotypes and the frequency of Tfh cells in whole blood | month 0 and month 1 | No |