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

Medical University of Graz

Status: Unknown

Conditions: Neuroblastoma; Microbial Colonization; Children, Only

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

Study type: Interventional

Funder types: Other

Identifiers

NCT03545542

0001

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 1 month to 8 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Neuroblastoma group

Experimental group

Description:

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.

Treatment:

Diagnostic Test: Initial breath volatile organic compounds

Diagnostic Test: Final breath volatile organic compounds

Diagnostic Test: Final microbiome

Diagnostic Test: Breath volatile organic compounds under chemotherapy

Diagnostic Test: Initial fecal microbiome

Diagnostic Test: Final fecal volatile organic compounds

Diagnostic Test: Fecal volatile organic compounds under chemotherapy

Diagnostic Test: Microbiome under chemotherapy

Diagnostic Test: Initial fecal volatile organic compounds

Control group

Other group

Description:

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.

Treatment:

Diagnostic Test: Initial breath volatile organic compounds

Diagnostic Test: Initial fecal microbiome

Diagnostic Test: Initial fecal volatile organic compounds