Investigating the Microbiome and Volatile Organic Compound Profile of Children With Neuroblastoma

NCT03545542 | Unknown

• 1 other identifier: 0001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Malignant tumors may lead to a catabolic state with loss of muscle and adipose tissue. The full picture of catabolism is termed cachexia and is associated with significant morbidity and mortality of cancer patients. Although the full picture is rarely observed up to 50% of children with cancer suffer from significant malnourishment. Additionally to tumor-induced catabolism, side-effects of chemotherapy may be problematic for the patients. In this regard up to 60% of children suffer from gastrointestinal mucositis presenting with nausea, vomiting, diarrhea or constipation and abdominal pain. In the worst case, mucositis may lead to bacterial translocation with life-threatening inflammatory response. Clinically this may require a reduction of the dosage or the number of chemotherapy cycles resulting in reduced effectivity. Up to now the therapy of mucositis is only symptomatic. Recent research of the applicant has shown a significant reduction of Lactobacilli in mice with neuroblastoma (a malignant childhood tumor). The dysbiosis was associated with catabolism, increased gut permeability and inflammation. Astonishingly, chemotherapy alone also leads to a significant reduction of Lactobacilli compared to sham mice, which may be linked to the development of mucositis clinically. Overall, the intestinal microbiome seems to play an essential role in the development of tumor-associated catabolism and chemotherapy-induced mucositis. Aim: The aim of this project is to determine if the changes in the intestinal microbiome observed in mice can also be seen in children with neuroblastoma. Methods: One part of the study will include 10 children with neuroblastoma (inclusion after verification of the diagnosis) and 10 healthy controls. The fecal microbiome will be determined by 16S-ribosomal deoxyribonucleic acid (rDNA) pyrosequencing. Volatile organic compounds in the breath will be sampled and measured by Gas Chromatography/Mass Spectroscopy. A basic science human work package will address the question if there are differences. In the second part serial investigations in children with neuroblastoma will assess whether or not these patients show alterations of the intestinal microbiome under chemotherapy.

Conditions

Microbial Colonization; Neuroblastoma; Children, Only

Keywords

Microbiome; Volatile organic compounds; Neuroblastoma

Outcome Measures

Primary Outcomes (2)

• Difference of alpha and beta diversity, relative abundance of fecal bacteria at different levels (phylum, class, order, family and genus levels) between neuroblastoma and control group

  Alpha and beta diversity, relative bacterial abundance at different levels in percent.

  Neuroblastoma group: within 48h after diagnosis, before initiation of chemotherapy. Control group: within 24h after obtaining informed consent.

• Change of alpha and beta diversity, relative abundance of fecal bacteria at different levels (phylum, class, order, family and genus levels) under chemotherapy in the neuroblastoma group

  Alpha and beta diversity, relative bacterial abundance at different levels in percent.

  Within 48h after diagnosis, before initiation of chemotherapy; 1 week after each chemotherapy cycle and 3 weeks after the end of chemotherapy.

Secondary Outcomes (7)

• Difference of anthropometric data between neuroblastoma and control group.

  Neuroblastoma group: within 48h after diagnosis. Control group: within 24h after obtaining informed consent.

• Change of anthropometric data under chemotherapy in the neuroblastoma group

  Within 48h after diagnosis, before initiation of chemotherapy; 7 days after completion of each chemotherapy cycle and 3 weeks after the end of chemotherapy.

• Change of mucositis score under chemotherapy in the neuroblastoma group.

  Within 48h after diagnosis, before initiation of chemotherapy; 7 days after completion of each chemotherapy cycle and 3 weeks after the end of chemotherapy.

• Difference of breath volatile organic compounds between neuroblastoma and control group.

  Neuroblastoma group: within 48h after diagnosis. Control group: within 24h after obtaining informed consent.

• Difference of stool volatile organic compounds between neuroblastoma and control group.

  Neuroblastoma group: within 48h after diagnosis. Control group: within 24h after obtaining informed consent.

Study Arms (2)

Neuroblastoma group

EXPERIMENTAL

10 children with neuroblastoma. Inclusion after verification of diagnosis and informed consent. Sampling of fecal microbiome (Initial microbiome, microbiome under chemotherapy, final microbiome), fecal volatile organic compounds (initial fecal volatile organic compounds, fecal volatile organic compounds under chemotherapy and final fecal volatile organic compounds) and breath organic volatile compounds (initial breath organic compounds, breath volatile organic compounds under chemotherapy and final breath volatile organic compounds). Samples will be taken after verifying diagnosis before initiation of chemotherapy, 1 week after completion of each cycle and 3 weeks after the end of chemotherapy.

Diagnostic Test: Initial fecal microbiome; Diagnostic Test: Initial fecal volatile organic compounds; Diagnostic Test: Initial breath volatile organic compounds; Diagnostic Test: Microbiome under chemotherapy; Diagnostic Test: Fecal volatile organic compounds under chemotherapy; Diagnostic Test: Breath volatile organic compounds under chemotherapy; Diagnostic Test: Final microbiome; Diagnostic Test: Final fecal volatile organic compounds; Diagnostic Test: Final breath volatile organic compounds

Control group

OTHER

10 children without gastro-intestinal or pulmonary disease as age and sex matched controls to the neuroblastoma group. Patients will be recruited from paediatric surgery. Inclusion after informed consent. Sampling of fecal microbiome (initial fecal microbiome), fecal volatile organic compounds (initial fecal volatile organic compounds) and breath organic volatile compounds (initial breath volatile organic compounds). Samples will be taken as age and sex matched controls for the neuroblastoma group. Sampling will be done once after obtaining informed consent.

Diagnostic Test: Initial fecal microbiome; Diagnostic Test: Initial fecal volatile organic compounds; Diagnostic Test: Initial breath volatile organic compounds

Interventions

Initial fecal microbiome DIAGNOSTIC_TEST

Stool sampling for fecal microbiome analysis by 16S rDNA pyrosequencing. Neuroblastoma group and Control group.

Control group; Neuroblastoma group

Initial fecal volatile organic compounds DIAGNOSTIC_TEST

Volatile organic compound analysis of stool samples by gas chromatography/mass spectroscopy Neuroblastoma group and Control group.

Control group; Neuroblastoma group

Initial breath volatile organic compounds DIAGNOSTIC_TEST

Breath sampling for organic compound analysis by gas chromatography/mass spectroscopy Neuroblastoma group and Control group.

Control group; Neuroblastoma group

Microbiome under chemotherapy DIAGNOSTIC_TEST

Stool sampling under chemotherapy of children in neuroblastoma group (1 sample 1 week after completion of each chemotherapy cycle). Chemotherapy according to Société Internationale d´Onclogie Pediatrique Neuroblastoma Group (SIOPEN) guidelines

Neuroblastoma group

Fecal volatile organic compounds under chemotherapy DIAGNOSTIC_TEST

Stool sampling under chemotherapy of children in neuroblastoma group (1 sample 1 week after completion of each chemotherapy cycle). Chemotherapy according to SIOPEN guidelines. Neuroblastoma group

Neuroblastoma group

Breath volatile organic compounds under chemotherapy DIAGNOSTIC_TEST

Breath sampling under chemotherapy of children in neuroblastoma group (1 sample 1 week after completion of each chemotherapy cycle). Chemotherapy according to SIOPEN guidelines. Neuroblastoma group

Neuroblastoma group

Final microbiome DIAGNOSTIC_TEST

Stool sampling 3 weeks after completion of chemotherapy Neuroblastoma group

Neuroblastoma group

Final fecal volatile organic compounds DIAGNOSTIC_TEST

Stool sampling 3 weeks after completion of chemotherapy Neuroblastoma group

Neuroblastoma group

Final breath volatile organic compounds DIAGNOSTIC_TEST

Breath sampling 3 weeks after completion of chemotherapy Neuroblastoma group

Neuroblastoma group

Eligibility Criteria

• Age: 1 Month - 8 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 2-8 years
• Neuroblastoma group: verified neuroblastoma
• Control group: absence of pulmonary or gastro-intestinal disease
• Written parental informed consent obtained

You may not qualify if:

• Active gastro-intestinal or pulmonary disease
• Antibiotic or probiotic treatment within 3 weeks before sampling
• Negative parental informed consent

Sponsors & Collaborators

• Medical University of Graz: lead

Study Sites (1)

Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria

Graz, Styria, 8036, Austria

RECRUITING

MeSH Terms

Conditions

Communicable Diseases; Neuroblastoma

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Christoph Castellani, MD

  Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christoph Castellani, MD

CONTACT

+43/316/385; christoph.castellani@medunigraz.at

Georg Singer, MD

CONTACT

+43/316/385; georg.singer@medunigraz.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Neuroblastoma group: Children with neuroblastoma enrolled after verification of diagnosis. Sampling before initiation of chemotherapy and under chemotherapy. Control group: healthy children without gastro-intestinal or pulmonary disease recruited from paediatric surgery.

Study Record Dates

• First Submitted: May 7, 2018
• First Posted: June 4, 2018
• Study Start: May 7, 2018
• Primary Completion: June 30, 2022
• Study Completion: December 31, 2022
• Last Updated: February 25, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)