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

NCT00909012 | Completed

• 1 other identifier: 455-08
• Study Type: interventional
• Target: 114
• Locations: 4 countries
• Sites: 6

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.

Conditions

Phenylketonuria

Keywords

phenylketonuria; docosahexaenoic acid; visually evoked potential; choice-reaction time

Outcome Measures

Primary Outcomes (1)

• latency of visually evoked potentials

  assessed basally (before intervention start) and at the end of the 6 month intervention period

Secondary Outcomes (3)

• fatty acid composition of plasma phospholipids

  assessed basally (before intervention start) and at the end of the 6 month intervention period

• fine motor skills

  assessed basally (before intervention start) and at the end of the 6 month intervention period

• test of reaction time

  assessed basally (before intervention start) and at the end of the 6 month intervention period

Study Arms (5)

1

PLACEBO COMPARATOR

Dietary Supplement: high oleic sunflower oil

2

EXPERIMENTAL

Dietary Supplement: microalgal oil

3

EXPERIMENTAL

Dietary Supplement: microalgal oil

4

EXPERIMENTAL

Dietary Supplement: microalgal oil

5

EXPERIMENTAL

Dietary Supplement: microalgal oil

Interventions

high oleic sunflower oil DIETARY_SUPPLEMENT

placebo, which does not provide DHA

1

microalgal oil DIETARY_SUPPLEMENT

the supplement provides 20 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)

2

Eligibility Criteria

• Age: 5 Years - 13 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead
• European Union: collaborator

Study Sites (6)

Zentrum für Kinder- und Jugendmedizin

Heidelberg, D-69120, Germany

Location

LMU

München, D-80337, Germany

Location

Department of Pediatrics, San Paolo Hospital Milano

Milan, Italy

Location

Department of Pediatrics, IFIMAV-Hospital M. Valdecill

Santander, Spain

Location

The Childrens Hospital Birmingham

Birmingham, United Kingdom

Location

Department of Pediatrics, Great Ormond Street Hospital for Sick Children

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30544518 RESULT

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Berthold Koletzko, Prof.

  Dr. von Hauner Children Hospital, Ludwig-Maximilians-Universitaet Muenchen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: April 22, 2009
• First Posted: May 27, 2009
• Study Start: May 1, 2009
• Primary Completion: July 1, 2011
• Study Completion: March 1, 2013
• Last Updated: August 22, 2022

Record last verified: 2022-08

Locations

IT (1); ES (1); DE (2); GB (2)