Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Other Dietary Supplements

Pembrolizumab

Immunomodulating Agents

Atezolizumab

Sulfalene

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Immunologic Factors

Bifidobacterium

Active arm: Pooled fecal microbiota capsules of 1 donor selected based on their fecal abundance in Faecalibacterium prausnitzii, Bifidobacterium longum, Akkermansia muciniphila and Fusobacterium spp. after screening and metagenomic analysis of 10 donors with high-fiber diets (\>30g/day).

anti PD1 therapy every 2-3 weeks

Control arm: no intervention before anti PD1 therapy

Pooled fecal microbiota capsules of 1 donor selected based on their fecal abundance in Faecalibacterium prausnitzii, Bifidobacterium longum, Akkermansia muciniphila and Fusobacterium spp. after screening and metagenomic analysis of 10 donors with high-fiber diets (\>30g/day).

anti PD1 therapy every 2-3 weeks

Microbiota Transplant plus anti PD1 therapy

anti PD1 therapy

Sergio Serrano-Villar, MD

Pilar Garrido, MD

Sergio Serrano-Villar, MD, PhD

The gut microbiota can modulate the effectiveness of cancer therapies, especially immunotherapy. Manipulating the microbial populations in patients with advanced lung cancer through fecal microbiota transplantation from healthy individuals or from long-term survivors to advanced lung cancer will enhance the efficacy of immunotherapy.

Lung cancer is a leading cause of mortality worldwide, and its treatment and prognosis are being revolutionized by immunotherapy. The gut microbiome has been shown able to modulate the antitumor efficacy of immunotherapeutic agents in pre-clinical models, demonstrating that patients can be stratified into responders and nonresponders to immunotherapy on the basis of their microbiota composition. Fecal microbiota transplants have demonstrated to improve the efficacy of immunotherapy in animal models. In this study, investigators will include 20 stage III/V non-small cell lung cancer naïve for PD/PD L-1 inhibitors that require treatment in monotherapy or combined with chemotherapy as consolidation strategy after concurrent chemotherapy and radiotherapy (stage III), upfront treatment (stage IV patients with PDL1 status \> 50%) or as second line strategy for those patients with advanced disease who progressed to chemotherapy alone. The participants will be randomized to receive either fecal microbiota capsules from 3 donors selected based on the fecal abundance of bacterial taxa shown to correlate with a greater response to immunotherapy or not, in combination with the PDL/PDL1 agent. The primary outcome will be safety. The secondary outcomes will be treatment response (iRECIST criteria). Investigators will also examine engraftment of donor's microbiota on host microbiota using Illumina DNA shotgun sequencing, changes in the bacterial metabolism using metaproteomics, and in the plasma metabolite fingerprint by untargeted mass spectrometry in bacterial and plasma samples, and changes in peripheral immune cells subpopulations and antitumoral immunity. MORELIA could improve the prognosis of a lung cancer in a subset of patients with limited therapeutic options and inform on how to exploit host-microbiota interactions with tailored fecal microbiota transplantation to boost the clinical response to immunotherapy in advanced cancer.

Microbiota Transplant in Advanced Lung Cancer Treated With Immunotherapy

The safety variables (vital signs, physical examinations, symptoms, laboratory test results and the occurrence of adverse events) will be assessed at each visit. The incidence of adverse events will be categorized by severity and related to the time of occurrence. Changes in physical examinations, changes in laboratory test results (hematology, biochemistry and urinalysis tests) from screening period, and change of vital signs will be summarized and analyzed by the descriptive statistics. Adverse events will be defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. v5.0

Immunotherapy Response Evaluation Criteria in Solid Tumors-iRECIST

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Syndrome

Polycystic Ovary Syndrome

Dysbiosis

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Natriuretic Agents

Reproductive Control Agents

Drospirenone

Ethinyl Estradiol

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Estradiol

Polyestradiol phosphate

Contraceptive Agents

Drospirenone and ethinyl estradiol combination

Contraceptives, Oral

Contraceptive Agents, Female

Mineralocorticoid Receptor Antagonists

Mineralocorticoids

Hormones

Hormone Antagonists

Diuretics

Diuretics, Potassium Sparing

Contraceptives, Oral, Hormonal

Contraceptive Agents, Hormonal

Estrogens

Acidophilus

Participants are healthy women and there are no interventions.

Participants are PCOS patients and only will be given lifestyle interventions.

Participants are PCOS patients and will be given lifestyle interventions + Probiotic Agent interventions.

Participants are PCOS patients and will be given lifestyle intervention + Oral contraceptive interventions.

1. Balance the diet;
2. Limit high-calorie and high-fat food intake, reduce eating out, and establish regular eating habits;
3. Monitor body weight, avoid sedentary, get more sun and regular activities;
4. Mental health regulation.

Lifestyle intervention

Patients have to take a probiotic powder (product name: Tangwen Tai, lactobacillus plantarum LP45 + Lactobacillus acidophilus La28 + Bifidobacterium lactobacillus BAL531) twice a day for three months.

Probiotic Agent

The patient needs to take drospirenone ethinyl estradiol tablets (trade name: Yousi Yue) 1 tablet daily for 3 months.

Oral contraceptive

Rong Chen, Ph. D.

Xu Zhang, master

Rong Chen, Ph. D

Xu Zhang, Master

Polycystic ovary syndrome (PCOS) has a significant impact on women's health, but its pathogenesis is not yet clear. Dysbiosis of gut microbiota may play a role in the pathological change of PCOS. Most of the current researches are still limited to the use of amplicon sequencing to compare the basic taxonomic differences of gut microbiota between PCOS patients and normal controls. Overall analysis of microbiome species, genes, function, metabolism, and immunity in PCOS is still lacked. In this research, we would perform metagenomic sequencing to find the characteristics of gut microbiota of PCOS and to explore their correlations with metabolic, immune, and clinical symptoms. Finally, different interventions (lifestyle interventions, lifestyle interventions + oral probiotic, lifestyle interventions+ compound oral contraceptives) would be used to explore the change of gut microbiome in PCOS patients. This research will not only help the understanding of the pathophysiology of PCOS, but also provide a reference for the selection of clinical treatment options.

1. Data quality assurance: ① all inspections and measurements will be performed by either the hospital or the sequencing company personnel according to standard operating procedures (SOPs), except for saliva and stool samples, which will be self-collected by patients. For sample collection, we will provide text descriptions of the SOPs as well as video instruction. Designated staff will be assigned for support and can be contacted if participants have any queries concerning sample collection; ② a case report form (CRF) will be prepared according to the current SOPs, and detailed instructions will be provided to ensure consistency in data collection. At the same time, each CRF will be properly stored at least 5 years for verification and backtracking; ③ all experimental data will be logged into the database to ensure information accuracy based on the existing data; ④ we will keep the contact information of each participant, remind them of precautions during participation, and conduct regular follow-ups.
2. Sample size determination: The number of participants is based on comparable sample sizes in the literature. In this trial, there will be 50 healthy individuals (control group) and 150 PCOS (polycystic ovary syndrome) patients. The 150 PCOS patients will be randomly assigned to three intervention groups. This sample size accounts for a plausible insufficiency of data caused by patient dropouts and withdrawals before the study is completed. The participation cycle is of approximately four months, followed by a 2-year follow-up.
3. Metagenomic sequencing technology Metagenomic sequencing is the main technique used in this study. Metagenomics, also known as economics, was first proposed by Handelman and studies the molecular composition of microbial populations, their interactions, and gene functions.

   In medicine, metagenomics compares the structural and functional changes of human microbial communities under normal and disease states. It can analyze the diversity and the functional differences of microbial communities from healthy individuals and from patients with diseases, thus determine how diseases relate to changes in the microbial communities and in their respective metabolic networks. Therefore, metagenomics provides theoretical evidence for disease prevention, detection, and treatment. At present, the internationally renowned Human Microbiome Project (HMP, http://www.hmpdacc.org/) and the Metagenomics of the Human Intestinal Tract (MetaHIT) are typical applications of metagenomics in medicine.

   \[Metagenomic species, genes, and functional annotation\]

   ① Data quality control: the sequenced raw data will contain a certain amount of low-quality data, so quality control must be performed. Only high-quality data can correctly reflect the actual occurrence of microorganisms in the sample.

   ② Metagenome assembly: based on Clean Data, individual samples will be assembled separately at first, then reads that do not participate in the assembling above will be combined and mixed for assembly. This will increase the sequencing depth of low-abundance species in each sample and provide more sequencing information for each species.

   ③ Gene prediction: MetaGeneMark will be used for gene prediction based on single samples and mixed-assembled scaftigs. The redundancy of all predicted genes will be reduced to obtain a Uniq gene set. Then, the Clean Data of each sample will be compared to the gene set and the abundance of the gene set will be determined for each sample.

   ④ Species annotation: Clean Data will be used for quality control. It will be compared with an annotated according to reference genome databases of bacteria, archaea, viruses, and fungi from NCBI. A species abundance table will be obtained for each sample at different classification levels.

   ⑤ Functional annotation: functional annotation and abundance statistics will be based on the Uniq gene set and the KEGG database.

This study will collect 50 healthy participants and 150 PCOS participants. At the same time, 150 patients with PCOS will be randomly divided into the lifestyle intervention group, lifestyle interventions + Probiotic Agent group, lifestyle intervention + oral contraceptive group by random number table method.

Polycystic ovary syndrome (PCOS) is a syndrome of endocrine disorders characterized by sparse ovulation or anovulation, high androgen or insulin resistance, and polycystic ovary. PCOS is a woman-specific disease, so participants must be women.

The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of PCOS.

The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of Polycystic Ovary Syndrome.

According to national laws and regulations, human genetic resources may not be provided abroad.

Based on the gene and species composition of each sample, the Chao1 and Shannon indexes, as well as the observed OTUs (operational taxonomic units), will be calculated in order to identify the differences in gene and species diversity for each group.

The Spearman correlation coefficient between genes will be calculated, and genes with strong correlation will be grouped into one cluster, as a CAG. The abundance of CAGs in each sample will be determined Furthermore, the significantly enriched species in the control and PCOS groups will be enumerated for network display.

The LEfSe discriminant analysis will be used to screen for significant differences between groups. The dimensionality reduction will be implemented by LDA, and the impact of function difference will be evaluated to obtain the LDA score and identify significantly different functions between groups.

For the obtained species, genes, or functions with significant difference, the correlation between them and clinical indicators will be calculated, and key biomarkers with significant and strong correlation will be identified.

Use glucose tolerance and insulin test (75gOGTT+insulin) to assess whether the patient has insulin resistance, as well as the level of insulin resistance.

Six-sex-hormone tests, one of the clinical examination items, will be performed to measure androgen levels in the subjects.

Peking Union Medical College

Peking Union Medical College Hospital

Carcinoma

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Herbal and Botanical

Cola

Patients undergoing lower GI endoscopy without any colorectal adenoma or carcinoma.

Patients undergoing lower GI endoscopy with presence of colorectal adenoma detected.

Patients diagnosed with colorectal cancer and referred to surgical carcinoma resection.

Colon biopsies

The purpose of this study is the investigation of new host-microbiome interactions promoting adenoma formation and adenocarcinoma progression. For that purpose, the investigators will collect saliva, stool and colon biopsy specimens from patients referred to colonoscopy or surgical resection of colorectal tumor. Besides, a questionnaire about diet, lifestyle and medical history will be collected. Sample analysis will involve simultaneous characterization of host and microbiota genomic and transcriptomic components.

Investigation of the Role of the Microbiome in the Pathogenesis of Colorectal Adenoma and Carcinoma

Host microbiome composition and abundance data will be generated from saliva, stool and colonic biopsies with amplicon-based 16S ribosomal RNA sequencing. This data will be correlated to CRC risk factors collected in a questionnaire covering lifestyle, diet and medical history as well as host genomic and transcriptomic profiling generated by targeted gene sequencing and microarray-based gene expression profiling.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Microbiota Transplant in Advanced Lung Cancer Treated With Immunotherapy	NCT04924374	Lung Cancer	Microbiota Tran... anti PD1 therap...	18 Years -	Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of PCOS.	NCT03843736	Polycystic Ovar...	Lifestyle inter... Probiotic Agent Oral contracept...	18 Years - 45 Years	Peking Union Medical College Hospital
Investigation of the Role of the Microbiome in the Pathogenesis of Colorectal Adenoma and Carcinoma	NCT02947607	Colorectal Aden...	Colon biopsies	18 Years -	Universitaire Ziekenhuizen KU Leuven
The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of PCOS.	NCT03843736	Polycystic Ovar...	Lifestyle inter... Probiotic Agent Oral contracept...	18 Years - 45 Years	Peking Union Medical College Hospital

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