Ignite Creation Date:
2024-05-06 @ 8:26 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06380387
Status:
RECRUITING
Last Update Posted:
2024-04-23
First Post:
2024-02-21
Brief Title:
Whole Body Metabolism in Children Before and After Treatment of CNS Tumor
Sponsor:
Rigshospitalet Denmark
Organization:
Rigshospitalet Denmark
Study Overview
Official Title:
Whole Body Metabolism in Children Before and After Treatment of CNS Tumor
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
At the center of pediatric oncology in Copenhagen the investigators experience that the children with brain tumor more or less have a healthy body with normal skeletal muscle mass and are physical active to the same level as their friends at the same age The treatment period for brain tumor is approximately two years After the treatment period the children are more sedative with less interest in coming out doing physical activities and thus the investigators suspect that they have altered hormonal response low skeletal muscle mass and perhaps are in risk of developing metabolic syndrome
By comparing children with newly diagnosed CNS tumor with children finished treated for CNS tumor we wish to describe the metabolic path during the approximately two years treatment period these children go through These results will also be compared with results from healthy controls
The investigators aim to include 10 children aged 6-18 years with newly diagnosed CNS tumor 10 children aged 6-18 years finished treated for CNS tumor and 10 healthy controls aged 6-18 years By using stable isotope technique the investigators will investigate systemic fat glucose and protein metabolism together with liver protein degradation and glucose production Furthermore by using DXA scan the investigators will describe the quality and distribution of skeletal muscle Lastly the investigators will determine the skeletal muscle signal pathway and metabolism in skeletal muscle via the Bergström biopsy technique in vastus lateralis
By comparing children with newly diagnosed CNS tumor with children finished treated for CNS tumor we wish to describe the metabolic path during the approximately two years treatment period these children go through These results will also be compared with results from healthy controls
The investigators aim to include 10 children aged 6-18 years with newly diagnosed CNS tumor 10 children aged 6-18 years finished treated for CNS tumor and 10 healthy controls aged 6-18 years By using stable isotope technique the investigators will investigate systemic fat glucose and protein metabolism together with liver protein degradation and glucose production Furthermore by using DXA scan the investigators will describe the quality and distribution of skeletal muscle Lastly the investigators will determine the skeletal muscle signal pathway and metabolism in skeletal muscle via the Bergström biopsy technique in vastus lateralis
Detailed Description:
By comparing children with newly diagnosed CNS tumor with children finished treated for CNS tumor the investigators wish to describe the metabolic path during the approximately two years treatment period these children go through These results will also be compared with results from healthy controls
Trial design and time frame
A prospective non-randomized cross-sectional study
There will be three different patient groups included
Patient group A Children with newly diagnosed CNS tumor
Patient group B Children finished treated for CNS tumor
Healthy controls Children admitted to the hospital at the Epilepsy monitor unit EMU
The trial will be conducted over a total of two days and takes place at the Department of Pediatrics and Adolescent Medicine Rigshospitalet and the Copenhagen Neuromuscular Center Department of Neurology Rigshospitalet
Study day 1 Is estimated to last approximately 2 hours
Study day 2 Is estimated to last approximately 8 hours
Study Day 1 The children will be DXA-scanned and complete life quality questionnaires and pain scores In some cases study day 1 will be done after study day 2 depending on the cancer treatment plan for each patient
Study Day 2 For the patients newly diagnosed with CNS tumor The investigators strive to conduct study day 2 within the first week of hospital admission due to newly diagnosed CNS tumor However the investigators do accept study day 2 being conducted within the first month after time of diagnoseThe subjects will arrive around 0800 at Copenhagen Neuromuscular Centre CNMC Rigshospitalet
On arrival EMLA local anesthetics cream will be applied on the skin of the children in order to minimize any discomfort that may occur during iv-insertion Two peripheral venous catheters are inserted one in the medial cubital vein for infusion of stable isotopes and one in a dorsal vein of the hand for blood sampling If the child has a central venous catheter CVK we will only insert one peripheral venous catheter in the medial cubital vein for infusion of the stable isotopes
After 1 hour and 45 minutes of basal tracer infusion basal blood samples are drawn time -15 and 0 for the determination of basal steady state tracer enrichments and hormone concentrations At time 0 a liquid mixed meal is provided Blood samples are drawn frequently for 6 hours relative to start of the test meal at 0 10 20 30 40 50 60 90 120 150 180 240 300 and 360 minutes24 25 If the child becomes upset or we for other reasons want to stop earlier than 6 hours we will use the already obtained results
The tracers In this study the investigators will intravenously infuse small amounts of metabolites labelled with stable isotopes in primed continuous intravenous infusions of D8-Phenylalanine D2-Tyrosine 13C18-Oleate acid D2-Glucose D5-Glycerol This method is well-established at both CIMT and CNMC and has been used investigating several of patients categories before Neonates ongoing study gastric sleeve elderly and neuromuscular patients
The tracers are prepared from the hospital pharmacy All tracers are purchased from Cambridge Isotope Laboratories Andover MA USA suitable for human use Stable isotopes are non-radioactive and naturally occurring in food eg in corn
Food intervention At time 0 120 minutes after infusion a liquid mixed meal adjusted by weight is given The meal consists of Intrinsically labelled D5-Phenylalanine and D3-Leucine labelled casein protein 13C16palmitate 13C6-Glucose in a mix of glucose casein protein and rape seed oil dissolved in water in an energy density of 50 CHO 35 fat and 15 protein Intrinsically labeled caseinate was produced via an infusion of D5-phenylalanine and D3leucine into a lactating cow to obtain enriched milk Foulumn Arhus University from which the caseinate fraction was isolated at Arla Foods according to Good Manufacturing Practice GMP and safety checked an store under appropriate regulatory conditions until use Nørre Vium Denmark following a previously described procedure
Analyses of blood samplesThe samples will be collected in syringes containing 10μL EDTAmL to prevent coagulation The blood is immediately centrifuged at 4oC to separate plasma from red blood cells The samples will be frozen in coded tubes and stored at -80C until analysis
Routine blood samples Will be analysed immediately at the Department of Clinical Biochemistry Rigshospitalet
- Blood samples include Insulin HbA1C Cholesterol HDL LDL triglycerides
Glucose and lactate will be analyzed ABL 700 immediately as the blood is drawn
Specific blood samples
Free fatty acids will be analyzed using fluorometry
Hormones catecholamines insulin incretins and glucagon will be analyzed using RIA and Elisa Methods respectively
Stable isotope enrichments in blood will be analyzed using Liquid chromatography-tandem mass-spectrometry LC-MSMS and gas chromatography combustion isotope ratio mass spectrometry GC-C-IRMS Thermo Scientific Palo Alto CA USA and Bremen Germany
Calculations Whole body metabolite quantitative kinetics will be calculated using Steeles equation for non-steady state adapted for analysis of stable isotopes under the post-absorptive conditions
Trial design and time frame
A prospective non-randomized cross-sectional study
There will be three different patient groups included
Patient group A Children with newly diagnosed CNS tumor
Patient group B Children finished treated for CNS tumor
Healthy controls Children admitted to the hospital at the Epilepsy monitor unit EMU
The trial will be conducted over a total of two days and takes place at the Department of Pediatrics and Adolescent Medicine Rigshospitalet and the Copenhagen Neuromuscular Center Department of Neurology Rigshospitalet
Study day 1 Is estimated to last approximately 2 hours
Study day 2 Is estimated to last approximately 8 hours
Study Day 1 The children will be DXA-scanned and complete life quality questionnaires and pain scores In some cases study day 1 will be done after study day 2 depending on the cancer treatment plan for each patient
Study Day 2 For the patients newly diagnosed with CNS tumor The investigators strive to conduct study day 2 within the first week of hospital admission due to newly diagnosed CNS tumor However the investigators do accept study day 2 being conducted within the first month after time of diagnoseThe subjects will arrive around 0800 at Copenhagen Neuromuscular Centre CNMC Rigshospitalet
On arrival EMLA local anesthetics cream will be applied on the skin of the children in order to minimize any discomfort that may occur during iv-insertion Two peripheral venous catheters are inserted one in the medial cubital vein for infusion of stable isotopes and one in a dorsal vein of the hand for blood sampling If the child has a central venous catheter CVK we will only insert one peripheral venous catheter in the medial cubital vein for infusion of the stable isotopes
After 1 hour and 45 minutes of basal tracer infusion basal blood samples are drawn time -15 and 0 for the determination of basal steady state tracer enrichments and hormone concentrations At time 0 a liquid mixed meal is provided Blood samples are drawn frequently for 6 hours relative to start of the test meal at 0 10 20 30 40 50 60 90 120 150 180 240 300 and 360 minutes24 25 If the child becomes upset or we for other reasons want to stop earlier than 6 hours we will use the already obtained results
The tracers In this study the investigators will intravenously infuse small amounts of metabolites labelled with stable isotopes in primed continuous intravenous infusions of D8-Phenylalanine D2-Tyrosine 13C18-Oleate acid D2-Glucose D5-Glycerol This method is well-established at both CIMT and CNMC and has been used investigating several of patients categories before Neonates ongoing study gastric sleeve elderly and neuromuscular patients
The tracers are prepared from the hospital pharmacy All tracers are purchased from Cambridge Isotope Laboratories Andover MA USA suitable for human use Stable isotopes are non-radioactive and naturally occurring in food eg in corn
Food intervention At time 0 120 minutes after infusion a liquid mixed meal adjusted by weight is given The meal consists of Intrinsically labelled D5-Phenylalanine and D3-Leucine labelled casein protein 13C16palmitate 13C6-Glucose in a mix of glucose casein protein and rape seed oil dissolved in water in an energy density of 50 CHO 35 fat and 15 protein Intrinsically labeled caseinate was produced via an infusion of D5-phenylalanine and D3leucine into a lactating cow to obtain enriched milk Foulumn Arhus University from which the caseinate fraction was isolated at Arla Foods according to Good Manufacturing Practice GMP and safety checked an store under appropriate regulatory conditions until use Nørre Vium Denmark following a previously described procedure
Analyses of blood samplesThe samples will be collected in syringes containing 10μL EDTAmL to prevent coagulation The blood is immediately centrifuged at 4oC to separate plasma from red blood cells The samples will be frozen in coded tubes and stored at -80C until analysis
Routine blood samples Will be analysed immediately at the Department of Clinical Biochemistry Rigshospitalet
- Blood samples include Insulin HbA1C Cholesterol HDL LDL triglycerides
Glucose and lactate will be analyzed ABL 700 immediately as the blood is drawn
Specific blood samples
Free fatty acids will be analyzed using fluorometry
Hormones catecholamines insulin incretins and glucagon will be analyzed using RIA and Elisa Methods respectively
Stable isotope enrichments in blood will be analyzed using Liquid chromatography-tandem mass-spectrometry LC-MSMS and gas chromatography combustion isotope ratio mass spectrometry GC-C-IRMS Thermo Scientific Palo Alto CA USA and Bremen Germany
Calculations Whole body metabolite quantitative kinetics will be calculated using Steeles equation for non-steady state adapted for analysis of stable isotopes under the post-absorptive conditions
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None