Healthy Volunteers Study

Official title

Vaginal Metabolome Healthy Volunteers Study

Overview

The purpose of this study is to examine the role of the bacterial environments and metabolites in the early detection and prediction of ovarian cancer development. Vaginal swabs and stool samples will be collected from healthy volunteers, or those without a known ovarian cancer diagnosis or genetic ovarian cancer risk. These samples will be compared to samples from participants with increased cancer risk and ovarian cancer diagnoses.

Detailed description

This study will examine the role of the microbiome and its metabolites in early detection and prediction of ovarian cancer development. It has been previously shown that the composition and function of the microbiome may play a role in the development and progression of several types of cancer. One proposed mechanism by which the microbiome may contribute to cancer development is through the production of certain metabolic byproducts. Such metabolites produced or modified by the microbiome have emerged as a prominent factor with potential local and systemic effects on the host, and were proposed to mediate the microbiome's contribution to cancer development. Microbial metabolites can promote cancer development by activating signaling pathways that promote cell growth and survival. In addition, the microbiota affects carcinogenesis through the release of carcinogenic molecules, such as genotoxins, and through the production of tumor-promoting metabolites. Furthermore, microbial metabolites have been studied as potential biomarkers for cancer, with some research suggesting that certain microbial metabolites may be able to distinguish between healthy individuals and those with cancer. The microbiome of the female reproductive tract is relatively understudied compared to the gut microbiome, but recent studies have shown that it is present and diverse in various parts of the reproductive tract such as the vagina, cervix, and fallopian tubes. however, a microbiome or metabolome signature predictive of ovarian cancer has not yet been established. Eligible individuals will be consented to provide a one-time, self-administered vaginal swab sample and stool sample. Clinical research assistants/coordinators, genetic counselors, and/or study physicians will consent patients and process and store the samples of consented participants. Participants will be provided a stool collection kit at the time of consent with instructions for providing the sample and sending it back to the laboratory.

Interventions

• Other Self-Administered Sample Collection
  Participants will collect vaginal swabs and a stool sample.

Primary outcome measures

• Microbiome Involvement [Time frame: One-time sample donation of vaginal swabs collected at the time of the patient's appointment. A subsequent stool sample will be provided within a week of the vaginal swab.]
• Predictive Model [Time frame: One-time sample donation of vaginal swabs collected at the time of the patient's appointment. A subsequent stool sample will be provided within a week of the vaginal swab.]

Eligibility criteria

Inclusion criteria

• has ovaries

Exclusion criteria

• genetic mutations which increase risk of ovarian cancer: BRCA1/2, BRIP1, PALB2, Lynch Syndrome (MLH1, MSH2/EPCAM, MSH6) and ATM
• no genetic testing results or unknown genetic status
• prior cancer diagnosis
• prior cancer treatment
• HRT use
• Antibiotic use (1 month prior to providing sample)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

United States · 1 center

• Abramson Cancer Center of the University of Pennsylvania — Philadelphia

Publications

• Manasa G, Mascarenhas RJ, Shetti NP, Malode SJ, Aminabhavi TM. Biomarkers for Early Diagnosis of Ovarian Carcinoma. ACS Biomater Sci Eng. 2022 Jul 11;8(7):2726-2746. doi: 10.1021/acsbiomaterials.2c00390. Epub 2022 Jun 28. PMID 35762531
• Manganaro L, Celli V, Viggiani V, Berardelli E, Granato T, Tartaglione S, Farina A, Catalano C, Angeloni A, Anastasi E. CT imaging phenotypes linked to CA125 and HE4 biomarkers are highly predictive in discriminating between hereditary and sporadic ovarian cancer patients. Tumour Biol. 2022;44(1):171-185. doi: 10.3233/TUB-211557. PMID 36093649
• Menon U, Karpinskyj C, Gentry-Maharaj A. Ovarian Cancer Prevention and Screening. Obstet Gynecol. 2018 May;131(5):909-927. doi: 10.1097/AOG.0000000000002580. PMID 29630008
• Cullin N, Azevedo Antunes C, Straussman R, Stein-Thoeringer CK, Elinav E. Microbiome and cancer. Cancer Cell. 2021 Oct 11;39(10):1317-1341. doi: 10.1016/j.ccell.2021.08.006. Epub 2021 Sep 9. PMID 34506740
• Levy M, Thaiss CA, Elinav E. Metabolites: messengers between the microbiota and the immune system. Genes Dev. 2016 Jul 15;30(14):1589-97. doi: 10.1101/gad.284091.116. PMID 27474437
• Cao Y, Oh J, Xue M, Huh WJ, Wang J, Gonzalez-Hernandez JA, Rice TA, Martin AL, Song D, Crawford JM, Herzon SB, Palm NW. Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites. Science. 2022 Oct 28;378(6618):eabm3233. doi: 10.1126/science.abm3233. Epub 2022 Oct 28. PMID 36302024
• Kroemer G, McQuade JL, Merad M, Andre F, Zitvogel L. Bodywide ecological interventions on cancer. Nat Med. 2023 Jan;29(1):59-74. doi: 10.1038/s41591-022-02193-4. Epub 2023 Jan 19. PMID 36658422
• Dmitrieva-Posocco O, Wong AC, Lundgren P, Golos AM, Descamps HC, Dohnalova L, Cramer Z, Tian Y, Yueh B, Eskiocak O, Egervari G, Lan Y, Liu J, Fan J, Kim J, Madhu B, Schneider KM, Khoziainova S, Andreeva N, Wang Q, Li N, Furth EE, Bailis W, Kelsen JR, Hamilton KE, Kaestner KH, Berger SL, Epstein JA, Jain R, Li M, Beyaz S, Lengner CJ, Katona BW, Grivennikov SI, Thaiss CA, Levy M. beta-Hydroxybutyrat PMID 35477756

Identifiers

NCT: NCT06962059 · UPCC 01025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗