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

Neuroblastoma Clinical Trial

Official title:

Investigating the Microbiome and Volatile Organic Compound Profile of Children With Neuroblastoma - a Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03545542
• Other study ID #: 0001
• Status: Recruiting
• Phase: N/A
• Start date: May 7, 2018
• Est. completion date: December 31, 2022

Study information

• Verified date: February 2020
• Source: Medical University of Graz
• Contact: Christoph Castellani, MD
• Phone: +43/316/385
• Email: christoph.castellani[@]medunigraz.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 8 Years

Eligibility

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

Related Conditions & MeSH terms

• Children, Only
• Communicable Diseases
• Infection
• Microbial Colonization
• Neuroblastoma

Intervention

Diagnostic Test:
• Initial fecal microbiome
Stool sampling for fecal microbiome analysis by 16S rDNA pyrosequencing. Neuroblastoma group and Control group.
• Initial fecal volatile organic compounds
Volatile organic compound analysis of stool samples by gas chromatography/mass spectroscopy Neuroblastoma group and Control group.
• Initial breath volatile organic compounds
Breath sampling for organic compound analysis by gas chromatography/mass spectroscopy Neuroblastoma group and Control group.
• Microbiome under chemotherapy
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
• Fecal volatile organic compounds under chemotherapy
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
• Breath volatile organic compounds under chemotherapy
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
• Final microbiome
Stool sampling 3 weeks after completion of chemotherapy Neuroblastoma group
• Final fecal volatile organic compounds
Stool sampling 3 weeks after completion of chemotherapy Neuroblastoma group
• Final breath volatile organic compounds
Breath sampling 3 weeks after completion of chemotherapy Neuroblastoma group

Locations

Country	Name	City	State
Austria	Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria	Graz	Styria

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	Difference of anthropometric data between neuroblastoma and control group.	Body weight (in kg) and height (in m) will be determined to calculate the body mass index (BMI in kg/m^2).	Neuroblastoma group: within 48h after diagnosis. Control group: within 24h after obtaining informed consent.
Secondary	Change of anthropometric data under chemotherapy in the neuroblastoma group	Body weight (in kg) and height (in m) will be determined to calculate the Body mass index (BMI in kg/m^2).	Within 48h after diagnosis, before initiation of chemotherapy; 7 days after completion of each chemotherapy cycle and 3 weeks after the end of chemotherapy.
Secondary	Change of mucositis score under chemotherapy in the neuroblastoma group.	Assessment of the mucositis score according to the WHO criteria (WHO handbook for reporting results of cancer Treatment; WHO Offset publication no 48) The score contains 5 subitems which are evaluated separately. At the end a total score is derived by adding the results of all items.; Subitem 1: oral mucosa; range 0 (best) to 4 (worst) Subitem 2: nausea and vomiting; range from 0 (best) to 4 (worst) Subitem 3: diarrhea; range from 0 (best) to 4 (worst) Subitem 4: constipation; range from 0 (best) to 4 (worst) Subitem 5: abdominal pain; range from 0 (best) to 4 (worst)	Within 48h after diagnosis, before initiation of chemotherapy; 7 days after completion of each chemotherapy cycle and 3 weeks after the end of chemotherapy.
Secondary	Difference of breath volatile organic compounds between neuroblastoma and control group.	Volatile organic compounds in ppb in the exhaled breath.	Neuroblastoma group: within 48h after diagnosis. Control group: within 24h after obtaining informed consent.
Secondary	Difference of stool volatile organic compounds between neuroblastoma and control group.	Volatile organic compounds in ppb in stool samples.	Neuroblastoma group: within 48h after diagnosis. Control group: within 24h after obtaining informed consent.
Secondary	Change of breath volatile organic compounds under chemotherapy in the neuroblastoma group.	Volatile organic compounds in ppb in the exhaled breath.	Within 48h after diagnosis, before initiation of chemotherapy; 1 week after each chemotherapy cycle and 3 weeks after the end of chemotherapy.
Secondary	Change of stool volatile organic compounds under chemotherapy in the neuroblastoma group.	Volatile organic compounds in ppb in stool samples.	Within 48h after diagnosis, before initiation of chemotherapy; 1 week after each chemotherapy cycle and 3 weeks after the end of chemotherapy.