Trial Title:
Whole Body Metabolism in Children Before and After Treatment of CNS Tumor
NCT ID:
NCT06380387
Condition:
CNS Tumor, Childhood
Conditions: Official terms:
Central Nervous System Neoplasms
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Basic Science
Masking:
None (Open Label)
Intervention:
Intervention type:
Dietary Supplement
Intervention name:
Meal
Description:
Liquid meal
Arm group label:
Meal intervention with stable isotopes
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.
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 diagnose.The subjects will arrive around 08.00, 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 minutes)[24], [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 (e.g. 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 [D3]leucine 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 samples:The samples will be collected in syringes containing 10μL
EDTA/mL 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-MS/MS) 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
Steele's equation for non-steady state adapted for analysis of stable isotopes under the
post-absorptive conditions.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patient group A: Children with newly diagnosed CNS tumor, included just before the
start of treatment or right after possible surgery.
- Patient group B: Children who have completed treatment for a CNS tumor within the
last month.
- Healthy controls: Children admitted to the EMU because of either
- Suspected convulsions
- Nocturnal EEG changes
- 6-18 years
- Signed informed consent to participation in the trial.
Exclusion Criteria:
- Inability to understand the purpose of the trial or cooperate in the conduction of
the experiments. For the children this will concern of course the parents or the
guardians of the child.
- Competing conditions at risk of compromising the results of the study.
- Participation in other trials that may interfere with the results.
- Intake of medications that may interfere with the results, evaluated by
investigator.
- Pregnancy or breastfeeding.
Gender:
All
Minimum age:
6 Years
Maximum age:
18 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Department of Pediatrics and Adolescent Medicine and Copenhagen Neuromuscular Center, Rigshospitalet
Address:
City:
Copenhagen
Zip:
2100
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Mette Cathrine Ørngreen, MD, DMSc
Phone:
35455935
Email:
mette.cathrine.oerngreen.01@regionh.dk
Investigator:
Last name:
Mette Cathrine Ørngreen, MD, DMSc
Email:
Principal Investigator
Start date:
March 23, 2023
Completion date:
December 2026
Lead sponsor:
Agency:
Rigshospitalet, Denmark
Agency class:
Other
Source:
Rigshospitalet, Denmark
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06380387
