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

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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

Tracking Information
First Submitted Date  ICMJE June 11, 2019
First Posted Date  ICMJE June 25, 2019
Last Update Posted Date August 26, 2019
Actual Study Start Date  ICMJE August 1, 2019
Estimated Primary Completion Date June 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2019)
  • Vaginal Maturation Index (VMI) [ Time Frame: Baseline, 8 weeks ]
    Change in the vaginal maturation index from baseline to 8 weeks
  • Vaginal pH [ Time Frame: Baseline, 8 weeks ]
    Change in the vaginal pH from baseline to 8 weeks
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 20, 2019)
  • 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.
  • 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.
  • 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
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Investigation of Microbiomes of Postmenopausal Women Looking for Outcomes and Response to Estrogen Therapy
Official Title  ICMJE IMPLORE Study: Investigation of Microbiomes of Postmenopausal Women Looking for Outcomes and Response to Estrogen Therapy
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Female Urogenital Diseases
  • Vaginal Atrophy
  • Postmenopausal Atrophic Vaginitis
  • Genitourinary Disease
  • Postmenopausal Symptoms
Intervention  ICMJE 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
Study Arms  ICMJE
  • Experimental: Conjugated Estrogens Cream
    0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks
    Intervention: Drug: Conjugated Estrogens Cream
  • No Intervention: Control Cohort
    No intervention will be given.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 20, 2019)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date June 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 55 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kyle P Norris, MD 2059967372 kpnorris@uabmc.edu
Contact: Sunita Patel 2059341704 sunitapatel@uabmc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03996603
Other Study ID Numbers  ICMJE IRB-300002968
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kyle P Norris, MD, University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kyle P Norris, MD University of Alabama at Birmingham
PRS Account University of Alabama at Birmingham
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP