Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Investigation of Microbiomes of Postmenopausal Women Looking for Outcomes and Response to Estrogen Therapy (IMPLORE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03996603
Recruitment Status : Recruiting
First Posted : June 25, 2019
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
Kyle P Norris, MD, University of Alabama at Birmingham

Brief Summary:
In this proposed pilot study, 16S ribosomal RNA (rRNA) gene sequencing will be used in the analysis of bacterial communities (microbiomes) in postmenopausal women with vulvovaginal atrophy (VVA) before and after eight weeks of vaginal estrogen use. The investigators plan to characterize the composition and dynamics of the microbiomes of the vagina, bladder, and rectum for quantitative and qualitative changes in the distribution of operational taxonomic units (OTUs) before and after eight weeks of local vaginal estrogen therapy. Although the vagina, bladder, and gut microbiomes have been increasingly independently studied, less is known about the interactions of the bacterial communities among the three environments as well as the dynamic relationship with menopausal status and vaginal estrogen therapy and the investigators seek to elucidate these relationships further.

Condition or disease Intervention/treatment Phase
Female Urogenital Diseases Vaginal Atrophy Postmenopausal Atrophic Vaginitis Genitourinary Disease Postmenopausal Symptoms Drug: Conjugated Estrogens Cream Phase 4

Detailed Description:

This is an open-label pilot study of vaginal estrogen therapy in postmenopausal participants with vulvovaginal atrophy. The investigators seek to evaluate the effects of vaginal estrogen therapy on the vaginal, urinary, and rectal bacterial communities (microbiomes) and assess the (i) quantitative change in relative abundance of Lactobacillus among the community composition of bacteria in the vagina, and (ii) to evaluate the vaginal maturation index (VMI), vaginal pH, and vaginal inflammatory biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF and correlate any notable changes with changes noted in the vaginal microbiome, and (iii and iv) observe for quantitative and qualitative changes in the distribution of operational taxonomic units (OTUs) among the bladder and rectal microbiomes. These changes will also be compared to the results yielded from the vaginal microbiome analysis. Additionally the investigators will assess for quantitative changes in the bladder and rectal inflammatory biomarkers (IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF) and correlate these findings with any notable changes in the bladder and rectal microbiomes. Furthermore, changes in these biomarkers will be compared with the data (inflammatory and microbial) yielded from vaginal sampling. Bio-specimens and patient questionnaires will be assessed at baseline and again after eight weeks of vaginal estrogen therapy.

20 participants will receive the intervention (vaginal estrogen therapy) for 8 weeks. 5 participants who meet the same inclusion/exclusion criteria will not receive the intervention and will be sampled at the same time points. The additional 5 participants are intended to serve as a control cohort to demonstrate stability of the microbiome over the study period. The 5 participants may be compared to the 20 participants receiving therapy but that is not part of the primary or secondary outcomes.

The investigators believe that examining the dynamic relationships of the genitourinary-rectal region is innovative and vital to validating the investigator's understanding and assumptions of the pathophysiology and treatment approaches of this disorder.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: IMPLORE Study: Investigation of Microbiomes of Postmenopausal Women Looking for Outcomes and Response to Estrogen Therapy
Actual Study Start Date : August 1, 2019
Estimated Primary Completion Date : June 1, 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Conjugated Estrogens Cream
0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks
Drug: Conjugated Estrogens Cream
0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks
Other Name: Premarin Vaginal Cream

No Intervention: Control Cohort
No intervention will be given.



Primary Outcome Measures :
  1. Quantitative change in relative abundance of Lactobacillus among the community composition of bacteria in the vagina as measured by 16S ribosomal RNA (rRNA) gene sequencing. [ Time Frame: Baseline, 8 weeks ]
    The quantitative change in relative abundance of Lactobacillus among the community composition of bacteria in the vagina will be assessed from baseline to 8 weeks. The investigators hypothesize that a pre-specified statistically significant quantitative increase in the relative abundance of Lactobacillus will be seen among the participants that receive treatment.


Secondary Outcome Measures :
  1. Vaginal Maturation Index (VMI) [ Time Frame: Baseline, 8 weeks ]
    Change in the vaginal maturation index from baseline to 8 weeks

  2. Vaginal pH [ Time Frame: Baseline, 8 weeks ]
    Change in the vaginal pH from baseline to 8 weeks

  3. Vaginal inflammatory biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF [ Time Frame: Baseline, 8 weeks ]
    Change in the vaginal inflammatory biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF from baseline to 8 weeks


Other Outcome Measures:
  1. Quantitative and qualitative changes in the distribution of operational taxonomic units (OTUs) in the bladder microbiome. [ Time Frame: Baseline, 8 weeks ]
    Quantitative and qualitative changes in the distribution of operational taxonomic units (OTUs) from baseline to 8 weeks.

  2. Quantitative and qualitative changes in the distribution of operational taxonomic units (OTUs) in the rectal microbiome. [ Time Frame: Baseline, 8 weeks ]
    Quantitative and qualitative changes in the distribution of operational taxonomic units (OTUs) from baseline to 8 weeks.

  3. Bladder inflammatory biomarkers (IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF) [ Time Frame: Baseline, 8 weeks ]
    Change in the concentration of bladder inflammatory biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF from baseline to 8 weeks

  4. Rectal inflammatory biomarkers (IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF) [ Time Frame: Baseline, 8 weeks ]
    Change in the concentration of rectal inflammatory biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF from baseline to 8 weeks



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Postmenopausal with vulvovaginal atrophy
  • Age ≥55 years old and a screening vaginal pH of ≥5.
  • Without menses for ≥12 months.
  • No uterovaginal or vaginal vault prolapse beyond the hymen.
  • No estrogen replacement within the last month (may come off current treatment, i.e. wash out, to join the study)

Exclusion Criteria:

  • Patients with BMI >35kg/m2
  • Any patients with infections requiring antibiotic or antifungal therapy during the study period.
  • Study patients may not use any vaginal suppositories, douches, or vaginal hygiene wipes within the month preceding enrollment. For patients already on hormone therapy, will be allowed to undergo a "wash out" period of estrogen or progesterone products for one month prior to enrollment.
  • Additional exclusions included patients with systemic conditions requiring immunosuppressive drugs, currently receiving chemotherapy, or history of pelvic radiation.
  • Any patients with contraindications to vaginal estrogen therapy including: vaginal bleeding of unknown etiology; known, suspected, or history of breast cancer or estrogen-dependent neoplasia; active DVT, PE, or h/o these conditions; active arterial thromboembolic disease (ie. stroke or MI) or h/o of these; known liver disease or thrombophilic disorders.
  • Current tobacco use.
  • Allergy to Premarin® or its constituents.
  • Concurrent use of steroid creams for other indications (ie. lichen sclerosis)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03996603


Contacts
Layout table for location contacts
Contact: Kyle P Norris, MD 2059967372 kpnorris@uabmc.edu
Contact: Sunita Patel 2059341704 sunitapatel@uabmc.edu

Locations
Layout table for location information
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Kyle P Norris, MD    205-934-5497    kpnorris@uabmc.edu   
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Layout table for investigator information
Principal Investigator: Kyle P Norris, MD University of Alabama at Birmingham
Layout table for additonal information
Responsible Party: Kyle P Norris, MD, Instructor Fellow, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT03996603    
Other Study ID Numbers: IRB-300002968
First Posted: June 25, 2019    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Kyle P Norris, MD, University of Alabama at Birmingham:
Genitourinary Syndrome of Menopause
Vaginal Atrophy
Vaginal Estrogen Therapy
Inflammatory Response
Microbial Colonization
Urinary Microbiome
Vaginal Microbiome
Rectal Microbiome
Conjugated Estrogen Cream
Additional relevant MeSH terms:
Layout table for MeSH terms
Vaginitis
Atrophic Vaginitis
Atrophy
Pathological Conditions, Anatomical
Vaginal Diseases
Genital Diseases, Female
Estrogens
Estrogens, Conjugated (USP)
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs