Quantitative Requirements of Docosahexaenoic Acid for Neural Function in Children With Phenylketonuria

Phenylketonuria Clinical Trial

Official title:

Quantitative Requirements of Docosahexaenoic Acid for Neural Function in Children With Phenylketonuria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00909012
• Other study ID #: 455-08
• Status: Completed
• Phase: N/A
• Start date: May 2009
• Est. completion date: March 2013

Study information

• Verified date: August 2022
• Source: Ludwig-Maximilians - University of Munich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: March 2013
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 13 Years

Eligibility

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

Related Conditions & MeSH terms

• Phenylketonuria
• Phenylketonurias

Intervention

Dietary Supplement:
• high oleic sunflower oil
placebo, which does not provide DHA
• microalgal oil
the supplement provides 20 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
• microalgal oil
the supplement provides 40 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
• microalgal oil
the supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
• microalgal oil
the supplement provides 130 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)

Locations

Country	Name	City	State
Germany	Zentrum für Kinder- und Jugendmedizin	Heidelberg
Germany	LMU	Muenchen
Italy	Department of Pediatrics, San Paolo Hospital Milano	Milano
Spain	Department of Pediatrics, IFIMAV-Hospital M. Valdecill	Santander
United Kingdom	The Childrens Hospital Birmingham	Birmingham
United Kingdom	Department of Pediatrics, Great Ormond Street Hospital for Sick Children	London

Sponsors (2)

Lead Sponsor	Collaborator
Ludwig-Maximilians - University of Munich	European Union

Countries where clinical trial is conducted

Germany,  Italy,  Spain,  United Kingdom, 

References & Publications (1)

Demmelmair H, MacDonald A, Kotzaeridou U, Burgard P, Gonzalez-Lamuno D, Verduci E, Ersoy M, Gokcay G, Alyanak B, Reischl E, Müller-Felber W, Faber FL, Handel U, Paci S, Koletzko B. Determinants of Plasma Docosahexaenoic Acid Levels and Their Relationship — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	latency of visually evoked potentials		assessed basally (before intervention start) and at the end of the 6 month intervention period
Secondary	fatty acid composition of plasma phospholipids		assessed basally (before intervention start) and at the end of the 6 month intervention period
Secondary	fine motor skills		assessed basally (before intervention start) and at the end of the 6 month intervention period
Secondary	test of reaction time		assessed basally (before intervention start) and at the end of the 6 month intervention period