Ignite Creation Date:
2024-07-17 @ 11:02 AM
Last Modification Date:
2024-10-26 @ 3:33 PM
Study NCT ID:
NCT06486597
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2024-05-17
Brief Title:
Whole Body Metabolism in Children With Cerebral Palsy With Low Skeletal Muscle Mass
Sponsor:
Rigshospitalet Denmark
Organization:
Rigshospitalet Denmark
Study Overview
Official Title:
Whole Body Metabolism in Children With Cerebral Palsy With Low Skeletal Muscle Mass
Status:
RECRUITING
Status Verified Date:
2024-06
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 pediatrics in Copenhagen the investigators experience that the children with CP with low skeletal muscle mass have more complications and admission after for example surgery is prolonged due to these complications In order to prevent malnutrition and energy insufficiency as well as obesity and cardiometabolic disorders in adulthood and with the aim of defining biomarkers for energy needs the investigators wish to determine energy and protein needs in children with CP
The investigators wish to investigate the whole-body metabolism in children with cerebral palsy CP and compare the results with results from healthy children The investigators aim to include 10 children aged 2-18 years with CP with low skeletal muscle mass and 10 healthy controls aged 2-18 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
The investigators wish to investigate the whole-body metabolism in children with cerebral palsy CP and compare the results with results from healthy children The investigators aim to include 10 children aged 2-18 years with CP with low skeletal muscle mass and 10 healthy controls aged 2-18 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:
Trial design and time frame
A prospective non-randomized cross-sectional study
There will be two different groups included
Children with cerebral palsy with low skeletal muscle mass
Healthy controls Children admitted to the hospital at the Epilepsy monitor unit EMU for conditions not affecting metabolic function
The trial will be conducted over a total of five days and takes place at the Copenhagen Neuromuscular Centre Department of Neurology or Department of Pediatrics and Adolescent Medicine Rigshospitalet
Study Day 1 The patient will be DXA-scanned or fat mass will be measured by a fat caliper and the patient will complete quality of life questionnaire and pain scores
Study Day 2 Study type A The stable isotope infusion will take place The subjects will arrive around 0800 at Copenhagen Neuromuscular Centre CNMC Rigshospitalet or Department of Pediatrics and Adolescents medicine Rigshospitalet Otherwise the study will take place when the child is admitted for change of baclofen pump or minor surgery where they typically will be hospitalized for 1-3 days at Rigshospitalet or Skejby hospital at the Department of Pediatrics and Adolescents or the Orthopedic Departments
On arrival EMLA local anesthetics cream will be applied on the skin of the children 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 Most of the children already have a permanent catheter and in this case the permanent catheter will be used for infusion of stable isotopes
Background samples will be collected before the start of tracer infusion After 1 hour and 45 minutes of basal tracer infusion basal blood samples are drawn time -15 and -30 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 regularly for 6 hours and more frequently the first hour after the test meal ingestion at 0 10 20 30 40 50 60 90 120 180 240 300 and 360 minutes If the child becomes upset or the investigators for other reasons want to stop earlier than 6 hours the already obtained blood and urine samples will be analyzed and included in the results
Study days 3 4 and 5 Study type B and C
These study days are optional to the families and the investigator For some families one study day is what they can fit into their calendar and the investigators want to respect that for those who accept to continue the study for more than one day the following days are included
The doubly labeled water technique measures energy consumption over a prolonged period in our study for 1 week A drink with doubly labeled water will be ingested and energy expenditure is measured by urine and blood sampling This method is repeated at 3 hours and 4 hours after the drink intake and again at day 3 and day 7 Furthermore a drink with 13C will be ingested and breath tests collected in vacutainers with straws will be collected for analysis of energy expenditure Measuring energy expenditure with these two less non-invasive methods and comparing results with the detailed meal test will pave the way for developing simple diagnostic markers for metabolism in the children
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
A prospective non-randomized cross-sectional study
There will be two different groups included
Children with cerebral palsy with low skeletal muscle mass
Healthy controls Children admitted to the hospital at the Epilepsy monitor unit EMU for conditions not affecting metabolic function
The trial will be conducted over a total of five days and takes place at the Copenhagen Neuromuscular Centre Department of Neurology or Department of Pediatrics and Adolescent Medicine Rigshospitalet
Study Day 1 The patient will be DXA-scanned or fat mass will be measured by a fat caliper and the patient will complete quality of life questionnaire and pain scores
Study Day 2 Study type A The stable isotope infusion will take place The subjects will arrive around 0800 at Copenhagen Neuromuscular Centre CNMC Rigshospitalet or Department of Pediatrics and Adolescents medicine Rigshospitalet Otherwise the study will take place when the child is admitted for change of baclofen pump or minor surgery where they typically will be hospitalized for 1-3 days at Rigshospitalet or Skejby hospital at the Department of Pediatrics and Adolescents or the Orthopedic Departments
On arrival EMLA local anesthetics cream will be applied on the skin of the children 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 Most of the children already have a permanent catheter and in this case the permanent catheter will be used for infusion of stable isotopes
Background samples will be collected before the start of tracer infusion After 1 hour and 45 minutes of basal tracer infusion basal blood samples are drawn time -15 and -30 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 regularly for 6 hours and more frequently the first hour after the test meal ingestion at 0 10 20 30 40 50 60 90 120 180 240 300 and 360 minutes If the child becomes upset or the investigators for other reasons want to stop earlier than 6 hours the already obtained blood and urine samples will be analyzed and included in the results
Study days 3 4 and 5 Study type B and C
These study days are optional to the families and the investigator For some families one study day is what they can fit into their calendar and the investigators want to respect that for those who accept to continue the study for more than one day the following days are included
The doubly labeled water technique measures energy consumption over a prolonged period in our study for 1 week A drink with doubly labeled water will be ingested and energy expenditure is measured by urine and blood sampling This method is repeated at 3 hours and 4 hours after the drink intake and again at day 3 and day 7 Furthermore a drink with 13C will be ingested and breath tests collected in vacutainers with straws will be collected for analysis of energy expenditure Measuring energy expenditure with these two less non-invasive methods and comparing results with the detailed meal test will pave the way for developing simple diagnostic markers for metabolism in the children
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