Ignite Creation Date:
2024-05-06 @ 4:10 PM
Last Modification Date:
2024-10-26 @ 2:05 PM
Study NCT ID:
NCT04896281
Status:
RECRUITING
Last Update Posted:
2024-03-18
First Post:
2021-04-26
Brief Title:
Phenylalanine-free Diet for Patients With Secondary Hyperphenylalaninemia in ICU
Sponsor:
Chang Gung Memorial Hospital
Organization:
Chang Gung Memorial Hospital
Study Overview
Official Title:
Phenylalanine-free Diet Lowers the Blood Phenylalanine Levels in Patients With High Phenylalanine Level in the Intensive Care Unit
Status:
RECRUITING
Status Verified Date:
2024-03
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:
Hyperphenylalaninemia is not only present in patients with congenital phenylketonuria In adults with critical illness hyperphenylalaninemia is noted in some patients and is associated with high mortality rate Hyperphenylalaninemia can cause metabolic acidosis brain dysfunction and metabolic disturbance The investigators would like to see whether the phenylalanine-free milk for congenital phenylketonuria is also effective in lowering the blood phenylalanine concentrations in patients with critical illness in intensive care unit and hyperphenylalaninemia
Detailed Description:
Background
Patients in the intensive care unit often suffer from problems such as high metabolic rate and high tissue breakdown rate under the severe stress of critical diseases Phenylalanine is an amino acid in the human body and is rich in muscle tissue However current studies have found that if the concentration of phenylalanine in the blood is abnormally increased it may indicate that the tissue is decomposing in large quantities This phenomenon may be related to disease severity Our recent observational study of patients in the intensive care unit ICU found that patients with elevated blood phenylalanine had a four-fold increase in mortality within one year
The most common cause of phenylalanine concentration elevation in the blood is a rare disease that occurs in infants with congenital metabolic abnormalities called congenital phenylketonuria PKU The abnormally elevated phenylalanine concentration can lead to toxicity and cause brain hypoplasia mental retardation consciousness disturbance and even seizure These PKU patients must be treated with milk diet that contains low amount of phenylalanine in order to lower the phenylalanine concentrations At present in medicine although there have been clear medical care strategy for infants with congenital PKU there is still no clear medical care strategy for adult patients
Research purpose To investigate whether patients with high blood phenylalanine concentration in the intensive care unit can reduce the blood phenylalanine concentration by a diet without phenylalanine so as to develop personalized high-quality and specific treatments
Methods
The investigators aim to have complete study in 70 patients based on our previous study to recruit 70 patients with high phenylalanine the investigators need 300 ICU patients for screening
Intervention protocol
Once a plasma phenylalanine level of 95 μM is noted phenylalanine-free diet Phenex-2 Abbott Nutrition Ohio USA or Phenyl-Free 2 Mead Johnson Nutrition Minnesota USA is started as the only nutrition source for enteral feeding as per the recommendation of dieticians in the following 4 days The phenylalanine-free diet is free of phenylalanine but is enriched with protein potassium tyrosine and antioxidant micronutrients After the completion of the study diet will be back to normal diet for all patients
Study end points the 5-day study period completed
Blood sampling and examination for Phenylalanine measurement dry blood spot Fasting phenylalanine level will be measured by LCMS-MS using the dry blood spot method blood sample is collected by finger sting in all included patients in the next morning after informed consent signed Blood applied on filter cards is dried for at least 3 h at room temperature Dry blood spot cards are stored at room temperature for 0-6 days prior to analyses Phenylalanine concentrations in dry blood spot are measured with LC-MSMS using a calibration curve in 01 N HCl The report will be received one day after dry blood spot collected Once the result of measurement shows the concentration of phenylalanine 95 μM this patient is enrolled for formal study All enrolled patients will take the measurement of phenylalanine levels by dry blood spot every 12 hours for the following 4 days until study protocol finished
Phenylalanine measurement by UPLC
In the meanwhile fasting blood will be collected by venipuncture in EDTA-containing tubes on the morning of screening 2 and 4 days after diet intervention The collected blood will be used to measure phenylalanine level by UPLC ultra-performance liquid chromatography Plasma samples 100μL are precipitated with 10 sulfosalicylic acid After protein precipitation and centrifugation derivatization is initiated by AQC in acetonitrile Amino acids are then analyzed using the ACQUITY UPLC System consisting of a Binary Solvent Manager a Sample Manager and a Tunable UV detector The investigators use EmpowerTM 2 Software to control the system and collect data Separations are performed on a 21100mm ACQUITY BEH C18 column at a flow rate of 070mLmin The average intra-assay coefficient of variation is 26 for phenylalanine The total coefficient of variation is 27 for phenylalanine The detection limit is 33μM for phenylalanine The linear range is 25-500 μM
APACHE II scores Disease severity is evaluated by calculating APACHE II score on the first day of ICU admission
Patients in the intensive care unit often suffer from problems such as high metabolic rate and high tissue breakdown rate under the severe stress of critical diseases Phenylalanine is an amino acid in the human body and is rich in muscle tissue However current studies have found that if the concentration of phenylalanine in the blood is abnormally increased it may indicate that the tissue is decomposing in large quantities This phenomenon may be related to disease severity Our recent observational study of patients in the intensive care unit ICU found that patients with elevated blood phenylalanine had a four-fold increase in mortality within one year
The most common cause of phenylalanine concentration elevation in the blood is a rare disease that occurs in infants with congenital metabolic abnormalities called congenital phenylketonuria PKU The abnormally elevated phenylalanine concentration can lead to toxicity and cause brain hypoplasia mental retardation consciousness disturbance and even seizure These PKU patients must be treated with milk diet that contains low amount of phenylalanine in order to lower the phenylalanine concentrations At present in medicine although there have been clear medical care strategy for infants with congenital PKU there is still no clear medical care strategy for adult patients
Research purpose To investigate whether patients with high blood phenylalanine concentration in the intensive care unit can reduce the blood phenylalanine concentration by a diet without phenylalanine so as to develop personalized high-quality and specific treatments
Methods
The investigators aim to have complete study in 70 patients based on our previous study to recruit 70 patients with high phenylalanine the investigators need 300 ICU patients for screening
Intervention protocol
Once a plasma phenylalanine level of 95 μM is noted phenylalanine-free diet Phenex-2 Abbott Nutrition Ohio USA or Phenyl-Free 2 Mead Johnson Nutrition Minnesota USA is started as the only nutrition source for enteral feeding as per the recommendation of dieticians in the following 4 days The phenylalanine-free diet is free of phenylalanine but is enriched with protein potassium tyrosine and antioxidant micronutrients After the completion of the study diet will be back to normal diet for all patients
Study end points the 5-day study period completed
Blood sampling and examination for Phenylalanine measurement dry blood spot Fasting phenylalanine level will be measured by LCMS-MS using the dry blood spot method blood sample is collected by finger sting in all included patients in the next morning after informed consent signed Blood applied on filter cards is dried for at least 3 h at room temperature Dry blood spot cards are stored at room temperature for 0-6 days prior to analyses Phenylalanine concentrations in dry blood spot are measured with LC-MSMS using a calibration curve in 01 N HCl The report will be received one day after dry blood spot collected Once the result of measurement shows the concentration of phenylalanine 95 μM this patient is enrolled for formal study All enrolled patients will take the measurement of phenylalanine levels by dry blood spot every 12 hours for the following 4 days until study protocol finished
Phenylalanine measurement by UPLC
In the meanwhile fasting blood will be collected by venipuncture in EDTA-containing tubes on the morning of screening 2 and 4 days after diet intervention The collected blood will be used to measure phenylalanine level by UPLC ultra-performance liquid chromatography Plasma samples 100μL are precipitated with 10 sulfosalicylic acid After protein precipitation and centrifugation derivatization is initiated by AQC in acetonitrile Amino acids are then analyzed using the ACQUITY UPLC System consisting of a Binary Solvent Manager a Sample Manager and a Tunable UV detector The investigators use EmpowerTM 2 Software to control the system and collect data Separations are performed on a 21100mm ACQUITY BEH C18 column at a flow rate of 070mLmin The average intra-assay coefficient of variation is 26 for phenylalanine The total coefficient of variation is 27 for phenylalanine The detection limit is 33μM for phenylalanine The linear range is 25-500 μM
APACHE II scores Disease severity is evaluated by calculating APACHE II score on the first day of ICU admission
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