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

This study has been completed.
Sponsor:
Collaborator:
European Union
Information provided by (Responsible Party):
Koletzko - Office, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:
NCT00909012
First received: April 22, 2009
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

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 15 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.


Condition Intervention
Phenylketonuria
Dietary Supplement: high oleic sunflower oil
Dietary Supplement: microalgal oil

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Quantitative Requirements of Docosahexaenoic Acid for Neural Function in Children With Phenylketonuria

Resource links provided by NLM:


Further study details as provided by Ludwig-Maximilians - University of Munich:

Primary Outcome Measures:
  • latency of visually evoked potentials [ Time Frame: assessed basally (before intervention start) and at the end of the 6 month intervention period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • fatty acid composition of plasma phospholipids [ Time Frame: assessed basally (before intervention start) and at the end of the 6 month intervention period ] [ Designated as safety issue: Yes ]
  • fine motor skills [ Time Frame: assessed basally (before intervention start) and at the end of the 6 month intervention period ] [ Designated as safety issue: No ]
  • test of reaction time [ Time Frame: assessed basally (before intervention start) and at the end of the 6 month intervention period ] [ Designated as safety issue: No ]

Enrollment: 114
Study Start Date: May 2009
Study Completion Date: March 2013
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1 Dietary Supplement: high oleic sunflower oil
placebo, which does not provide DHA
Experimental: 2 Dietary Supplement: microalgal oil
the supplement provides 35 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Experimental: 3 Dietary Supplement: microalgal oil
the supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Experimental: 4 Dietary Supplement: microalgal oil
the supplement provides 140 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Experimental: 5 Dietary Supplement: microalgal oil
the supplement provides 225 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)

  Eligibility

Ages Eligible for Study:   5 Years to 13 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00909012

Locations
Germany
Zentrum für Kinder- und Jugendmedizin
Heidelberg, Germany, D-69120
LMU
Muenchen, Germany, D-80337
Italy
Department of Pediatrics, San Paolo Hospital Milano
Milano, Italy
Spain
Department of Pediatrics, IFIMAV-Hospital M. Valdecill
Santander, Spain
United Kingdom
The Childrens Hospital Birmingham
Birmingham, United Kingdom
Department of Pediatrics, Great Ormond Street Hospital for Sick Children
London, United Kingdom
Sponsors and Collaborators
Ludwig-Maximilians - University of Munich
European Union
Investigators
Principal Investigator: Berthold Koletzko, Prof. Dr. von Hauner Children Hospital, Ludwig-Maximilians-Universitaet Muenchen
  More Information

No publications provided

Responsible Party: Koletzko - Office, Prof., Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT00909012     History of Changes
Other Study ID Numbers: 455-08
Study First Received: April 22, 2009
Last Updated: June 19, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Ludwig-Maximilians - University of Munich:
phenylketonuria
docosahexaenoic acid
visually evoked potential
choice-reaction time

Additional relevant MeSH terms:
Phenylketonurias
Amino Acid Metabolism, Inborn Errors
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases

ClinicalTrials.gov processed this record on November 27, 2014