Susan L. Rosenthal - US grants

Introduction: Sexually transmitted diseases (STUD) are a significant public health problem, especially among adolescents. In order to plan effective interventions for adolescents, longitudinal studies need to be conducted that will aid in the understanding of the psychological and behavioral issues that underlie the initial STD acquisition as well as the responses of the adolescent following acquisition. Aims: The first aim is to examine the complex relationships of the components of adolescent development to adolescent girl's sexual behavior and the consequences of sexual behavior on adolescent girls. Components of adolescent development include: cognitive, psychosexual, and biological maturation, knowledge and perceptions, sociocultural context, and the adolescent's ability to manage situations. The second aim is to examine, longitudinally, the relationship of the developmental changes in psychological development and sexual practices for adolescent girls. This aim will examine changes in adolescents' beliefs and behaviors after they acquire or do not acquire an STD. Methods: One hundred and seventy-five adolescent girls, ages 12-15, will be recruited from their source of primary care in an urban adolescent clinic. The sample will consist of a racially mixed cohort, with both sexually inexperienced and experienced girls. They will be evaluated every 6 months for three years. At each 6-month visit, psychological/behavioral data will be collected by interview and standardized assessment measures. The sexually experienced subjects will receive a pelvic exam and Pap smear, and standard procedures will be used for the diagnosis of trichomonas, gonorrhea, and Chlamydia infections. Once yearly, a polymerase chain reaction assay for human papillomavirus will be performed and blood will be obtained for syphilis serology and herpes simplex virus serotyping. Confidential testing for human immunodeficiency virus will occur at the beginning and the end of the study. Subjects with positive results will be referred to their primary care provider. Medical charts will be reviewed to document any STD that occurs between study appointments. Clinical Significance: Behavioral/psychological strategies will continue to be the fundamental approach to the prevention of sexually transmitted diseases in adolescents. This longitudinal study will provide data regarding adolescent development across the adolescent age span and levels of sexual experience. The adolescent's style of coping as it relates to her perception of sexually transmitted diseases will be characterized. This study will improve our understanding of adolescents who place themselves at risk for sexually transmitted diseases.

DESCRIPTION (Adapted from the applicant's description): Sexually transmitted diseases (STDs) are a major health problem for adolescents. The development of new methods for STD prevention such as topical microbicides is of high priority. To be effective, microbicides will need to be accepted and used. Adolescent-specific interventions will be needed to promote microbicide use among adolescents. The current proposal examines developmental factors that are associated with use of microbicide-like formulations among adolescent girls and explores the attitudes of significant individuals (boys, mothers, health care providers) who impact adolescent girls' decision-making. Specific Aims: 1) To describe how adolescent females and males and significant adults (mothers of adolescent girls and health care providers) anticipate using a topical microbicide. The applicant will address research questions focused on their familiarity with the products, aspects that foster use, barriers to use, and how these perceptions vary across different groups. 2) To evaluate how discussion of use, initial use, and sustained use varies as a function of developmental characteristics (cognitive functioning and decision-making, psychosexual maturation, sociocultural context), and the experience with the product. Methods: The first specific aim will be accomplished by conducting focus groups of adolescent males, adolescent females, mothers, and health care providers. The second specific aim and relevant hypotheses will be tested by recruiting 200 adolescent girls (14 to 21 years) to participate in a study during which they have an opportunity to use approved intravaginal contraceptive products. These girls will be followed weekly for six months to determine use of the product and their experiences using or not using the product. Significance: This work will provide important new information regarding factors that will influence microbicide use by adolescent girls. The results of our research will be critical in guiding the development of adolescent-specific interventions that will foster the acceptability and use of microbicides, and in doing so, will result in better control of STDs among adolescents.

female; health behavior; adolescence (12-20); antiinfective agents; culture; social psychology; psychosexual development; cognition; growth /development; decision making; behavioral /social science research tag; human subject; clinical research;

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: HIV continues to be a growing epidemic despite various efforts to prevent and treat this disease. Potential methods of prevention include microbicides, creams or gels that can be used by women inside the vagina to protect them from acquiring infections during sexual intercourse. Microbicides are being developed however, the methods to test safety are not sensitive enough. In studies of two potential microbicides, the scientists found that the women who used the medications were more susceptible to HIV than those who did not. Early animal and human studies did not predict safety in these drugs therefore more sensitive methods are needed. Optical coherence tomography (OCT) holds promise as a high resolution, non-invasive method to evaluate the lining (epithelium) of the vagina and cervix. In animal studies, it can detect epithelial changes not detected by colposcopy, the current gold standard for safety evaluation in humans. Hypotheses: Hypothesis 1: In the study dosing, N-9 will provide minimal, if any, changes in the cervicovaginal epithelium. Hypothesis 2: OCT will detect minor changes in the cervicovaginal epithelium not detected by colposcopy. Specific Aims and Procedures (summary): The primary aim of the study is to evaluate whether regular use of an over-the-counter formulation of N-9 will result in epithelial toxicity detectable by OCT but not by colposcopy. Volunteers will be randomized to use either an over-the-counter spermicide, Nonoxynol-9 (Conceptrol ) or placebo gel (Hydroxyethylcellulose - HEC, a constituent in over-the-counter vaginal medications) intravaginally twice daily for 5.5 days. After the initial screening visit, women will be evaluated by OCT and colposcopy at Visit 1 (day 0), Visit 2 (day 6) and Visit 3 (day 13). Before and after treatment, OCT and colposcopy findings will be compared. The secondary aim of the study is to describe women's motivation and barriers to potential participation in a vaginal product safety study and to understand women's perceptions of the OCT and colposcopy experience. This secondary aim is hypothesis-generating and therefore no planned hypotheses are put forth. A series of open-ended questions over the course of three audio-recorded semi-structured interviews will address the topics of motivations, barriers, and perceptions. The analytic plan for these qualitative data will enable themes to be identified and summarized for each topic. Experimental Design (summary): Reproductive-aged (18-45 years) women will be targeted for enrollment in this study. They will be recruited with the use of flyers and study announcements on the UTMB daily announcements, and by word of mouth. They will have a telephone screening call in which questions about medical history will be asked. Women who are eligible will be screened for sexually transmitted diseases, cervical dysplasia and cancer, and pregnancy. Up to twenty-five women will be screened to enroll 18 women in the study;we anticipate that some will become ineligible because of their screening test results. Eighteen women will have an initial visit in which OCT and colposcopy will be performed. The participant will then receive either placebo (HEC) or Nonoxynol-9 to be used intra-vaginally twice daily for 5.5 days. The participant will return the day of the last dose for a repeat OCT and colposcopy genital examination. She will return a week later for OCT and colposcopy genital examination after a week without medication. She will be asked to be abstinent and to use no other products in the vagina during the course of the study. At each visit, she will also participate in an interview to explore her experience with being involved in the study, using the vaginal gel product, and undergoing the examination with OCT and colposcopy. Significance (summary): New methods of detection of epithelial changes after use of vaginal microbicides are needed in order to ensure the safety of these products. If OCT is determined to detect changes not noted on colposcopy, as we have seen in animal studies, it has great potential to enhance our ability to develop safe vaginal medications for the prevention of HIV and potentially help to slow the rate of acquisition of this disease.

DESCRIPTION (provided by applicant): The Belmont Report's concept of justice means adolescents should participate in studies regarding sexually transmitted infections, given their high rates of infection. Yet they are also a vulnerable population, which means they should benefit from parental guidance without being inappropriately influenced in their decision-making. Understanding parent-adolescent discordance about willingness to participate (WTP) helps develop strategies to insure that both are comfortable with the final decision. Decision-making is influenced by developmental characteristics, thus, given the rapid changes during adolescence there will be changes over time. A safety trial of topical microbicides will be the context in which to examine WTP, allowing for applicability to other trial types. Specific Aims: 1) Describe the relationship between developmental characteristics (cognition and relevant experience, parenting and family variables) and WTP, attitudes towards privacy and parental influence, and discordance in the context of a study of STI prevention; 2) Describe the relationship between changes in developmental characteristics (cognition and relevant experience, parenting and family relationships) over time and WTP and attitudes towards privacy and parental influence, and discordance in WTP in the context of a study of STI prevention; 3) Describe adolescent-parent management of discordance as it relates to perceptions of the salient aspects of the trial and adolescent-parent interactional style as it relates to discordance and satisfaction with the final decision regarding participation. Methods: A multi-level strategy will be used to recruit 14-17 year old male and female adolescents and parents from primary care clinics. Data about non-participation will be obtained at all stages of decision-making in order to collect information about parents and adolescents who would normally not participate in research. The use of a hypothetical clinical trial allows for assessment of families who would not participate in trials. Parents and adolescents will be interviewed simultaneously by two different interviewers, and then complete a joint interview, which will be videotaped for coding of the interaction. To evaluate the impact of developmental change, participants will be re-interviewed one year later. Outcomes: This information will be used to develop and evaluate interventions designed to provide adolescents the opportunity to participate in studies with as much guidance as needed from parents and the autonomy to make their own decision.