Clinical trial NCT00909012: Quantitative Requirements of Docosahexaenoic Acid for Neural Function in Children With Phenylketonuria
Official title: Quantitative Requirements of Docosahexaenoic Acid for Neural Function in Children With Phenylketonuria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Phenylketonuria
Keywords: phenylketonuria
docosahexaenoic acid
visually evoked potential
choice-reaction time
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
Collaborators: name: European Union
First posted: 2009-05-27
Enrollment: 114
Sex: ALL
Minimum age (years): 5
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Patients with phenylketonuria (PKU) have an inborn error in the metabolism of the amino acid phenylalanine (Phe) and thus must follow a strictly controlled protein-restricted diet from early infancy. This protein-restricted diet is devoid of natural dietary sources of n-3 long chain polyunsaturated fatty acids (LC-PUFA), such as eggs, meat, milk or fish. Therefore, blood concentrations of n-3 LC-PUFA, especially of docosahexaenoic acid (DHA) are reduced in PKU children compared to healthy controls. DHA availability is considered important for optimal neurological function. Previous studies have shown that neural function of PKU children is improved by high dose supplementation of fish oil providing DHA, as shown by significant improvements of both visual evoked potential latencies and of fine motor skills and coordination, but no dose response relationship has been established so far.

This multicentric double-blind randomized trial aims at determining quantitative DHA requirements for optimal neural function in PKU children. Patients with classical PKU from several major treatment centers in Europe will be randomized to receive between 0 and 8 mg of DHA per kg body weight daily for a duration of 6 months. Biochemical (fatty acid composition of plasma phospholipids, lipoprotein metabolism and metabolic profiles), and functional testing (visual evoked potentials, fine motor skills, cognitive function and markers of immune function) will be performed at baseline and after 6 months. Intake per kg body weight will be related to outcome parameters and thus a possible dose response relationship will be defined. The results from this study are expected to contribute to the improvement of the diet of PKU patients, but they also have the potential to help defining quantitative DHA needs of healthy children.

The primary hypothesis is that supplementation with DHA improves visual function in children with PKU.


Eligibility criteria: Inclusion Criteria:

* Children with classical PKU, who have been diagnosed and treated from the newborn period onwards
* Classical PKU must have been established by a baseline plasma phenylalanine (PHE) level \>1200 µmol/L or detection of underlying mutations
* Children are clinically healthy besides classical PKU
* Good metabolic control (a minimum of 2 Phe-values during the last 6 months are needed with average Phe values being below 480 µmol/L in the last 6 months)
* No n-3 LC-PUFA supplementation for at least 6 months before enrolment
* Written informed consent of parents exists

Exclusion Criteria:

* Severe neurological symptoms
* History of neurological disease
* Children are unable to take DHA-capsules regularly
* Acute illness, especially infections at the time of clinical examination/testing
* Children with weight/height over the 97th percentile or below the 3rd percentile
* Known hypersensitivity to fish oil products

Primary outcomes:
measure: latency of visually evoked potentials
timeFrame: assessed basally (before intervention start) and at the end of the 6 month intervention period
Secondary outcomes:
measure: fatty acid composition of plasma phospholipids
timeFrame: assessed basally (before intervention start) and at the end of the 6 month intervention period
measure: fine motor skills
timeFrame: assessed basally (before intervention start) and at the end of the 6 month intervention period
measure: test of reaction time
timeFrame: assessed basally (before intervention start) and at the end of the 6 month intervention period
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Zentrum für Kinder- und Jugendmedizin
city: Muenchen
country: Germany
facility: LMU
city: Milano
country: Italy
facility: Department of Pediatrics, San Paolo Hospital Milano
city: Santander
country: Spain
facility: Department of Pediatrics, IFIMAV-Hospital M. Valdecill
city: Birmingham
country: United Kingdom
facility: The Childrens Hospital Birmingham
city: London
country: United Kingdom
facility: Department of Pediatrics, Great Ormond Street Hospital for Sick Children
Study officials:
affiliation: Dr. von Hauner Children Hospital, Ludwig-Maximilians-Universitaet Muenchen
name: Berthold Koletzko, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Demmelmair H, MacDonald A, Kotzaeridou U, Burgard P, Gonzalez-Lamuno D, Verduci E, Ersoy M, Gokcay G, Alyanak B, Reischl E, Muller-Felber W, Faber FL, Handel U, Paci S, Koletzko B. Determinants of Plasma Docosahexaenoic Acid Levels and Their Relationship to Neurological and Cognitive Functions in PKU Patients: A Double Blind Randomized Supplementation Study. Nutrients. 2018 Dec 7;10(12):1944. doi: 10.3390/nu10121944.