Clinical trial NCT02176603: Observational Study of Endothelial Dysfunction in Phenylketonuria
Official title: Observational, Investigator Initiated, Monocentric Study of the Endothelial Dysfunction in Adolescent and Adult Patients With Phenylketonuria Due to Phenylalanine Hydroxylase Deficiency
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Phenylketonuria
Endothelial Dysfunction
Keywords: phenylketonuria, endothelial dysfunction, CKD
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Johannes Gutenberg University Mainz
First posted: 2014-06-27
Enrollment: 51
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients aged ≥ 16 years with PKU diagnosed by newborn screening who are followed up in the Metabolic Unit of the Charité University Medical Center Berlin (Interdisciplinary Center for Metabolic Diseases, Dept. of Hepatology and Gastroenterology, as well as Dept. of Pediatric Endocrinology, Gastroenterology and Metabolic Diseases).

Brief summary: The purpose of this study is to determine whether adolescent and adult patients with phenylketonuria who are on long-term phenylalanine-restricted diet suffer from endothelial dysfunction.

Detailed description: The aim of the study is the examination of endothelial dysfunction and oxidative stress markers in adolescent and adult patients with phenylketonuria (PKU), in correlation to phenylalanine values und phenylalanine-restricted diet. 25-50 patients with PKU aged ≥16 years of age and a control group of 25 age- and sex-matched healthy volunteers will be included in the study.

Endothelial dysfunction will be measured by venous occlusion plethysmography on the lower legs in the PKU patients and in the control group. Wave velocity, aortic stiffness, and intima media thickness of the common carotid artery will be measured by vicorder and duplex ultrasound scanner in the PKU patients and in the control group. Analyses of phenylalanine metabolites and renal function will be performed only in the PKU patients, analyses of oxidative stress markers in the PKU patients and in the control group. Dietary protocols of the patients with PKU will be calculated for their daily phenylalanine, total protein, and calorie intake. Results of the study will be kept in the medical records and paper case report forms. Data will be analyzed only in pseudonymized form.

Eligibility criteria: Inclusion Criteria:

* phenylketonuria due to phenylalanine hydroxylase deficiency
* age ≥16 years

Exclusion Criteria:

* age \<16 years
* pregnancy or maternity
* late-treated phenylketonuria
* phenylketonuria due a defect in BH4 synthesis or BH4 regeneration

Primary outcomes:
measure: Post-ischaemic venous flow (measured in ml/min) in patients with PKU compared to healthy volunteers
timeFrame: 18 months
Secondary outcomes:
measure: Aortic pulse wave velocity in patients with PKU compared to healthy volunteers. Intima media thickness in patients with PKU compared to healthy volunteers.
timeFrame: 18 months
Other outcomes:
Locations:
Study officials:
affiliation: Johannes Gutenberg University Mainz, Germany
name: Julia B Hennermann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charite University, Berlin, Germany
name: Uwe Querfeld, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Briese S, Claus M, Querfeld U. Arterial stiffness in children after renal transplantation. Pediatr Nephrol. 2008 Dec;23(12):2241-5. doi: 10.1007/s00467-008-0894-y. Epub 2008 Jun 27.
citation: Ribas GS, Sitta A, Wajner M, Vargas CR. Oxidative stress in phenylketonuria: what is the evidence? Cell Mol Neurobiol. 2011 Jul;31(5):653-62. doi: 10.1007/s10571-011-9693-2. Epub 2011 Apr 23.
citation: Kracht D, Shroff R, Baig S, Doyon A, Jacobi C, Zeller R, Querfeld U, Schaefer F, Wuhl E, Schmidt BM, Melk A; 4C Study Consortium. Validating a new oscillometric device for aortic pulse wave velocity measurements in children and adolescents. Am J Hypertens. 2011 Dec;24(12):1294-9. doi: 10.1038/ajh.2011.147. Epub 2011 Aug 25.
citation: Hennermann JB, Roloff S, Gellermann J, Vollmer I, Windt E, Vetter B, Plockinger U, Monch E, Querfeld U. Chronic kidney disease in adolescent and adult patients with phenylketonuria. J Inherit Metab Dis. 2013 Sep;36(5):747-56. doi: 10.1007/s10545-012-9548-0. Epub 2012 Nov 9.
citation: Hennermann JB, Querfeld U. Unknown pathomechanisms of renal impairment in PKU. J Inherit Metab Dis. 2013 Nov;36(6):1087-8. doi: 10.1007/s10545-013-9652-9. Epub 2013 Sep 17. No abstract available.