Clinical trial NCT03545542: Investigating the Microbiome and Volatile Organic Compound Profile of Children With Neuroblastoma
Official title: Investigating the Microbiome and Volatile Organic Compound Profile of Children With Neuroblastoma - a Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Microbial Colonization
Neuroblastoma
Children, Only
Keywords: Microbiome
Volatile organic compounds
Neuroblastoma
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2018-06-04
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Neuroblastoma group: within 48h after diagnosis, before initiation of chemotherapy. Control group: within 24h after obtaining informed consent.
measure: 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
timeFrame: Within 48h after diagnosis, before initiation of chemotherapy; 1 week after each chemotherapy cycle and 3 weeks after the end of chemotherapy.
Secondary outcomes:
measure: Difference of anthropometric data between neuroblastoma and control group.
timeFrame: Neuroblastoma group: within 48h after diagnosis. Control group: within 24h after obtaining informed consent.
measure: Change of anthropometric data under chemotherapy in the neuroblastoma group
timeFrame: Within 48h after diagnosis, before initiation of chemotherapy; 7 days after completion of each chemotherapy cycle and 3 weeks after the end of chemotherapy.
measure: Change of mucositis score under chemotherapy in the neuroblastoma group.
timeFrame: Within 48h after diagnosis, before initiation of chemotherapy; 7 days after completion of each chemotherapy cycle and 3 weeks after the end of chemotherapy.
measure: Difference of breath volatile organic compounds between neuroblastoma and control group.
timeFrame: Neuroblastoma group: within 48h after diagnosis. Control group: within 24h after obtaining informed consent.
measure: Difference of stool volatile organic compounds between neuroblastoma and control group.
timeFrame: Neuroblastoma group: within 48h after diagnosis. Control group: within 24h after obtaining informed consent.
measure: Change of breath volatile organic compounds under chemotherapy in the neuroblastoma group.
timeFrame: Within 48h after diagnosis, before initiation of chemotherapy; 1 week after each chemotherapy cycle and 3 weeks after the end of chemotherapy.
measure: Change of stool volatile organic compounds under chemotherapy in the neuroblastoma group.
timeFrame: Within 48h after diagnosis, before initiation of chemotherapy; 1 week after each chemotherapy cycle and 3 weeks after the end of chemotherapy.
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria
state: Styria
Study officials:
affiliation: Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria
name: Christoph Castellani, MD
role: PRINCIPAL_INVESTIGATOR
References: