Biomarkers of Protocol Compliance and Product Adherence - Full Text View

Purpose

The purpose of this study is to compare tests of vaginal insertion of applicators(visual inspection of returned applicators (VIRA), inspection of returned applicators under ultraviolet (UV) light, and DNA/protein markers) to determine which, if any, warrant use in a clinical trial of a new vaginal microbicide. The study will also determine whether indicators of semen can be detected on applicators and the degree to which they correlate with reported intercourse, and the correlation between vaginal bacteria detected by a vaginal swab and those detected from the applicator. In addition, the study will determine whether several factors that may be encountered in a clinical trial are likely to affect detection of these markers, including storage for 30 days vs. 7 days, wiping applicators after use, the presence of gel, and inter- and intra-woman variability. The study will also assess safety.

Condition	Intervention
HIV Prevention	Other: HEC placebo gel applicators


Study Type:	Observational
Study Design:	Time Perspective: Prospective
Official Title:	Comparison of Objective Biomarkers of Protocol Compliance and Product Adherence With Classic Markers of Compliance and Adherence

Further study details as provided by CONRAD:

Primary Outcome Measures:

Sensitivity, specificity, PPV, and NPV of the following indicator of vaginal insertion: VIRA [ Time Frame: 7 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Number of applicators on which Y chromosome-associated genes can be detected and degree of correlation between detection and the number of days since last penile/vaginal intercourse [ Time Frame: 7 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Degree of correlation of vaginal species obtained from vaginal applicators and vaginal species obtained from vaginal swabs [ Time Frame: 7 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Sensitivity, specificity, PPV, and NPV of the following indicator of vaginal insertion: VIRA [ Time Frame: 30 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Sensitivity, specificity, PPV, and NPV of the following indicator of vaginal insertion: UV Light Inspection [ Time Frame: 7 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Sensitivity, specificity, PPV, and NPV of the following indicator of vaginal insertion: UV Light Inspection [ Time Frame: 30 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Sensitivity, specificity, PPV, and NPV of the following indicator of vaginal insertion: DNA sequences of vaginal bacteria [ Time Frame: 7 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Sensitivity, specificity, PPV, and NPV of the following indicator of vaginal insertion: DNA sequences of vaginal bacteria [ Time Frame: 30 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Sensitivity, specificity, PPV, and NPV of the following indicator of vaginal insertion: Immunohistochemical tests for protein markers [ Time Frame: 7 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Sensitivity, specificity, PPV, and NPV of the following indicator of vaginal insertion: Immunohistochemical tests for protein markers [ Time Frame: 30 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Number of applicators on which Y chromosome-associated genes can be detected and degree of correlation between detection and the number of days since last penile/vaginal intercourse [ Time Frame: 30 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Degree of correlation of vaginal species obtained from vaginal applicators and vaginal species obtained from vaginal swabs [ Time Frame: 30 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Difference in detection of these markers when applicators are processed within one week versus approximately 30 days after the participant's visit [ Time Frame: 30 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Difference in the sensitivity, specificity, NPV and PPV of detection of these markers when applicators are wiped off after removal from the vagina [ Time Frame: 7 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Difference in detection of these markers when gel is present, either from a current applicator insertion and gel expulsion or from previous and current applicator insertion and gel expulsion [ Time Frame: 7 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Difference in the sensitivity, specificity, NPV and PPV of detection of these markers when applicators are wiped off after removal from the vagina [ Time Frame: 30 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]
Difference in detection of these markers when gel is present, either from a current applicator insertion and gel expulsion or from previous and current applicator insertion and gel expulsion [ Time Frame: 30 days after insertion of vaginal applicators ] [ Designated as safety issue: No ]


Enrollment:	40
Study Start Date:	March 2013
Study Completion Date:	September 2013
Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Healthy women	Other: HEC placebo gel applicators Participants will handle, but not insert, 4 applicators containing HEC placebo gel. Participants will vaginally insert and removed 8 applicators containing HEC placebo gel. Gel will be expelled in to the vagina from only 2 applicators.

Detailed Description:

Screening tests will be performed to detect exclusion criteria. After confirming the absence of point-of-care exclusion criteria, four applicators (#1 to 4, "sham" applicators) will be handled by the participant, but not inserted into the vagina and the gel will be expelled into a waste container. Four applicators (#5 to 8) will be inserted into the participant's vagina, one at a time, by the investigator, removed, and then the gel will be expelled into a waste container. Two applicators (#9 and 10) will be inserted into the participant's vagina, one at a time, and gel will be expelled into the participant's vagina. Finally, two applicators (#11 and 12) will be inserted into the participant's vagina, one at a time, by the investigator, removed and then the gel expelled into a waste container. Applicators #11 and 12 will then be wiped clean with a paper towel. Thus, each participant will provide a total of 12 applicators, half of which will be processed within one week of her visit and half of which will be processed in approximately one month of her visit. Three readers blinded to the status of the applicators (sham, inserted with or without gel expulsion) will determine, by VIRA and UV light assessment, whether or not the applicators were inserted vaginally. Additional laboratory personnel, who will also be blinded to the status of the applicators, will process the applicators for DNA and protein markers of product adherence and protocol compliance.

Eligibility


Ages Eligible for Study:	18 Years to 50 Years (Adult)
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Healthy, non-pregnant, HIV-uninfected women

Criteria

Inclusion Criteria:

18 to 50 years old
In good health, as evidenced by history
No use of vaginal medications in the past 7 days
At least 3 days from the end of their last menses
Willing and able to comply with study procedures

Exclusion Criteria:

Surgery or biopsy of the vagina or cervix within 30 days
Have a history of a total hysterectomy (removal of the uterus and cervix)
Pregnancy
Positive buccal HIV test
Other conditions that, in the opinion of the investigator, would constitute contraindications to participation in the study or would compromise the ability to comply with study protocols, such as any major chronic illness or a major psychiatric disorder (e.g., schizophrenia)
Current participation in any other drug or device study, or any study which, in the opinion of the investigator, would jeopardize interpretation of results of this study

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01804023

Locations


United States, Virginia
Clinical Research Center, Eastern Virginia Medical School
Norfolk, Virginia, United States, 23507

Sponsors and Collaborators

CONRAD

Investigators


Principal Investigator:	Andrea Thurman, M.D.	Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA

More Information


Responsible Party:	CONRAD
ClinicalTrials.gov Identifier:	NCT01804023 History of Changes
Other Study ID Numbers:	D13-125
Study First Received:	March 1, 2013
Last Updated:	October 29, 2013
Health Authority:	United States: Institutional Review Board

ClinicalTrials.gov processed this record on September 29, 2016