[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT05026138":3,"trial-entities:NCT05026138":87,"trial-summary:NCT05026138":94},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":6,"overall_status":7,"completion_date":8,"status_verified_date":9,"last_update_date":10,"start_date":11,"sponsor_name":12,"lead_sponsor_class":13,"has_dmc":14,"brief_summary":15,"detailed_description":16,"conditions":17,"keywords":19,"study_type":26,"primary_purpose":14,"phases":27,"enrollment_info":28,"interventions":31,"primary_outcomes":32,"secondary_outcomes":37,"sex":44,"minimum_age":45,"maximum_age":46,"healthy_volunteers":47,"eligibility_criteria":48,"std_ages":53,"locations":57,"central_contacts":74,"overall_officials":79,"references":82,"see_also_links":83},"NCT05026138","210029","Natural History, Epidemiology and Pathogenesis of Severe HPV-Related Diseases (Neptune)","RECRUITING","2047-03-31","2026-06-26","2026-07-06","2021-11-17","National Institute of Allergy and Infectious Diseases (NIAID)","NIH",null,"Background:\n\nMost symptoms of human papillomaviruses (HPV) infection, do not cause serious health problems, but some do. As HPV can cause uncontrolled growth of infected cells, some people can develop benign skin lesions, larger warts, genital lesions, tumors or cysts that do not respond to treatment. Researchers want to learn why.\n\nObjective:\n\nTo better understand why some people are more likely than others to get sick from HPV infection, and why medicine or surgery is not always effective.\n\nEligibility:\n\nPeople aged 3 years and older who have had multiple outbreaks of HPV-related warts and\u002For lesions that do not respond to treatment. Healthy relatives are also needed.\n\nDesign:\n\nParticipants will be screened with a medical history, physical exam, and blood tests.\n\nParticipants may have study visits as an outpatient or an inpatient (admitted overnight to the NIH hospital) and be followed over several years by our doctors and researchers at the NIH.\n\nParticipants may have a cervical and\u002For anal Pap test. They may give samples of semen, cervicovaginal secretions, urine, saliva, or stool. Small pieces of skin, the inside of the cheek, and\u002For the gums may be collected with a punch or scrape biopsy to understand how HPV affect the growth of cells.\n\nMucus and skin may be collected by rubbing the area with a cotton swab. Collection areas may include the inside the mouth, nostrils, skin, genitals, and\u002For in or around the anus.\n\nBiopsies may be collected. If participants need to have a biopsy as part of medical care, then we may ask if extra samples can be collected for research. Biopsies we may collect are bone marrow, lymph node, genitals, or in or around the anus.\n\nParticipants may have leukapheresis. Blood is taken from a needle placed in one arm. A machine separates out the white blood cells. The rest of the blood is returned through a needle in their other arm.\n\nSamples may be used for genetic tests and\u002For to make special cells called induced pluripotent stem cells.\n\nParticipants may have follow-up visits once a year for 10 years.\n\nBenefits:\n\nWe are not testing new HPV treatments in this study and you might not benefit from participating. However, we may learn new information about your condition that we will share with you and your doctor. We may make recommendations for your medical care based on current accepted treatment.\n\nWhat we learn from you and other participants in this study might help other people. We hope we can use this information to develop new treatments and therapies in the future....","Study Design: This is a prospective, longitudinal natural history study. Total length of individual participation is 10 years.\n\nPrimary Objective: To define the clinical, immunologic, and genetic bases of severe disseminated, recurrent, and treatment-refractory HPV-related skin and mucosal disease.\n\nSecondary Objectives:\n\n1. Identify novel genetic defects associated with severe HPV-related diseases.\n2. Define the natural history of HPV infections on skin and mucosal tissue in immunocompromised hosts.\n3. Define the epidemiology of skin and mucosal HPV variants in immunocompromised hosts by next-generation sequencing.\n4. Define the distribution of immune cells in skin and mucosal surfaces of patients with severe HPV-related diseases and\n\nimmunologic correlates of HPV-disease progression.\n\nPrimary Endpoint: Identify novel immunologic and\u002For genetic determinants of the susceptibility to severe disseminated, recurrent, and\n\ntreatment-refractory HPV-related diseases.\n\nSecondary Endpoints: 1. Identify virologic, clinical, and immunologic predictors of progressive HPV-related diseases.\n\n2\\. Define the cellular and functional components involved in control or lack thereof of HPV infection in different cutaneous and\n\nmucosal surfaces.\n\nThe purpose of this study is to identify clinical and immunologic correlates of increased susceptibility to human papillomavirus (HPV) infections, HPV related dysplasia\u002Fcancer, or any other HPV-related clinical manifestations. We will enroll patients with disseminated, multifocal or recurrent HPV-related diseases refractory to standard-of-care medical or surgical interventions. Healthy family members household contacts, and\u002For sexual partners will also be enrolled as comparators. This protocol will allow long-term follow-up of patients with primary or acquired immunologic abnormalities associated with such increased susceptibility to HPV-related diseases. It will also allow periodic clinical and laboratory evaluation with collection of blood, biological fluids, tissue and mucosal swabs, and tissue biopsies for medically indicated purposes. Additional research studies on these samples will be aimed to identify genetic and immunologic bases of their HPV-related diseases and inform the development of specific and effective treatment interventions.",[18],"Human Papillomavirus",[20,21,22,23,24,25],"Mucosal Disease","Immunocompromised","Genetic Defects","Infection","Neoplasia","Natural History","OBSERVATIONAL",[],{"count":29,"type":30},850,"ESTIMATED",[],[33],{"measure":34,"description":35,"timeFrame":36},"Identify novel immunologic and\u002For genetic determinants of the susceptibility to severe disseminated, recurrent, and treatment-refractory HPV-related diseases.","To define the clinical, immunologic, and genetic bases of severe disseminated, recurrent, and treatment-refractory HPV-related skin and mucosal disease.","Throughout the study",[38,41],{"measure":39,"description":40,"timeFrame":36},"Identify virologic, clinical, and immunologic predictors of progressive HPV-related diseases","Identify novel genetic defects associated with severe HPV related diseases.",{"measure":42,"description":43,"timeFrame":36},"Define the cellular and functional components involved in control or lack thereof of HPV infection in different cutaneous and mucosal surfaces","Define the natural history of HPV infections on skin and mucosal tissue in immunocompromised hosts; Define the epidemiology of skin and mucosal HPV variants in immunocompromised hosts by next-generation sequencing; Define the distribution of immune cells in skin and mucosal surfaces of patients with severe HPV-related diseases and immunologic correlates of HPV-disease progression.","ALL","3 Years","100 Years",true,{"inclusion":49,"exclusion":51,"raw_text":52},[50],"The lack of complete response to 2 or more interventions is defined as treatment-refractory disease in the protocol, while the reappearance of a skin or mucosal lesion after complete resolution is defined as recurrence.",[],"* INCLUSION CRITERIA:\n\nInclusion Criteria for All Participants\n\n1. Aged \\>=3 years (except for household contacts and sexual partners of participants with HPV-related diseases, who must be aged 18 years and older).\n2. Able to provide informed consent or, if younger than 18, be accompanied by a parent(s)\u002Flegal guardian(s) who is able to provide informed consent.\n3. Willing to allow genetic testing on their collected biological samples.\n\nAdditional Inclusion Criteria for Participants with HPV-related Diseases\n\nHas severe, disseminated, recurrent, and treatment-refractory HPV infection, defined as one or more of the following confirmed by medical record review or participant health history:\n\n1. In participants without known primary or acquired immunodeficiency:\n\n   1. Multiple skin warts (\\>=5) recurrent\\* or refractory to standard-of-care interventions (eg, topical imiquimod, acetylsalicylic acid, cryotherapy, cantharidin, podophyllotoxin, bleomycin, cauterization, cidofovir, fluorouracil).\n   2. Concomitant skin warts (irrespective to recurrence or treatment response) AND any historical or current clinical and\u002For histologic or cytologic evidence of mucosal HPV-related diseases (oral, nasal, laryngeal, vaginal, anal, penile, or cervical).\n   3. Mucosal condyloma or other HPV-related diseases that are recurrent\\* or refractory to standard-of-care interventions.\n   4. Historical evidence of mucosal condyloma or any HPV-related diseases occurring irrespective of response to standard-of-care interventions and involving more than one mucosal site.\n2. In participants with known primary or acquired immunological defect (including idiopathic CD4 lymphopenia, immunosuppressive treatment, or HIV\u002FAIDS):\n\n   a. Any skin OR mucosal HPV-related diseases\n3. In any participant:\n\n   1. Recurrent invasive skin or mucosal HPV-related squamous cell carcinoma (HPV-SCC).\n   2. Historical or current histologic evidence of invasive HPV-SCC of any mucosal site in subjects with family history of HPV-SCC in 1 or more family members.\n\n      * The lack of complete response to 2 or more interventions is defined as treatment-refractory disease in the protocol, while the reappearance of a skin or mucosal lesion after complete resolution is defined as recurrence.\n\nAdditional Inclusion Criteria for Controls\n\n1\\. Biological relative, household contact, or sexual partner of the index participant (with HPV-related diseases) who meets one of the following criteria:\n\n1. does not have any historical or current clinical and\u002For histologic or cytologic evidence of skin or mucosal HPV-related diseases, or\n2. has historical or current clinical and\u002For histologic or cytologic evidence of skin or mucosal HPV-related diseases but does not meet the criteria to be enrolled in this study as a participant with HPV-related disease.\n\nEXCLUSION CRITERIA:\n\nIndividuals meeting any of the following criteria will be excluded from study participation:\n\n1. Laboratory abnormalities contraindicating research evaluations and procedures in patients without previous history of cytopenias: neutropenia (absolute neutrophil count \\\u003C500 cells\u002FmicroL) or thrombocytopenia (platelets \\\u003C10,000\u002FmicroL). Medical record review may be used to for determining eligibility if the laboratory tests were collected \\\u003C= 90 days prior to the screening visit.\n2. Inability to reliably keep research appointments and\u002For adhere to research procedures.\n3. Any condition that, in the opinion of the investigator, contraindicates participation in this study.\n\nAdditional Exclusion Criteria for Controls\n\n1\\. Has HPV-related disease that may indicate enrollment as an affected participant rather than as a healthy biological relative, household contact, or sexual partner.\n\nCo-enrollment guidelines: Participants may be co-enrolled in other studies; however, study staff should be notified of co-enrollment.",[54,55,56],"CHILD","ADULT","OLDER_ADULT",[58],{"facility":59,"status":7,"city":60,"state":61,"zip":62,"country":63,"contacts":64,"geoPoint":71},"National Institutes of Health Clinical Center","Bethesda","Maryland","20892","United States",[65],{"name":66,"role":67,"phone":68,"phoneExt":69,"email":70},"For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)","CONTACT","800-411-1222","TTY8664111010","prpl@cc.nih.gov",{"lat":72,"lon":73},38.98067,-77.10026,[75],{"name":76,"role":67,"phone":77,"email":78},"Andrea Lisco, M.D.","(301) 761-7122","andrea.lisco@nih.gov",[80],{"name":76,"affiliation":12,"role":81},"PRINCIPAL_INVESTIGATOR",[],[84],{"label":85,"url":86},"NIH Clinical Center Detailed Web Page","https:\u002F\u002Fclinicalstudies.info.nih.gov\u002Fcgi\u002Fdetail.cgi?A_2021-I-0029.html",{"nct_id":4,"conditions":88,"biomarkers":91},[89,90],"Human Papillomavirus Infection","Squamous Cell Carcinoma",[92,93],"CD4 Gene","HIV Infection",{"nct_id":4,"found":47,"summary":95,"prompt_version":105},{"design":96,"status":97,"heading":98,"summary":99,"follow_up":100,"word_count":101,"commitments":102,"compensation":103,"drugs_mentioned":104},"This is an observational study, meaning no specific treatments are being tested. It is a prospective, longitudinal natural history study, planning to enroll 850 participants.","completed","Understanding Severe HPV-Related Diseases (Neptune Study)","This study, called Neptune, aims to understand why some people get severe human papillomavirus (HPV) related diseases that are hard to treat. While most HPV infections don't cause serious problems, some can lead to growths, warts, or tumors that don't respond well to medicine or surgery. Researchers want to find out what makes certain individuals more likely to develop these severe forms of HPV disease and why treatments aren't always effective for them. The study is looking for people aged 3 and older who have had many outbreaks of HPV-related warts or lesions that haven't responded to treatment. Healthy family members are also needed. The main goal is to identify new immune system factors or genetic traits that make someone more susceptible to these severe HPV-related conditions.","Participants will be followed throughout the 10-year study period to identify immune and genetic factors.",127,"Participants will undergo a medical history review, a physical exam, and blood tests. Individual participation in the study will last for 10 years.","Not stated in the trial record.",[],"v2"]