- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00909012
Quantitative Requirements of Docosahexaenoic Acid for Neural Function in Children With Phenylketonuria
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.
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Heidelberg, Germany, D-69120
- Zentrum für Kinder- und Jugendmedizin
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Muenchen, Germany, D-80337
- LMU
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Milano, Italy
- Department of Pediatrics, San Paolo Hospital Milano
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Santander, Spain
- Department of Pediatrics, IFIMAV-Hospital M. Valdecill
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Birmingham, United Kingdom
- The Childrens Hospital Birmingham
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London, United Kingdom
- Department of Pediatrics, Great Ormond Street Hospital for Sick Children
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 2
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the supplement provides 20 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
the supplement provides 40 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
the supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
the supplement provides 130 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
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Placebo Comparator: 1
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placebo, which does not provide DHA
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Experimental: 3
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the supplement provides 20 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
the supplement provides 40 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
the supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
the supplement provides 130 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
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Experimental: 4
|
the supplement provides 20 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
the supplement provides 40 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
the supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
the supplement provides 130 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
|
Experimental: 5
|
the supplement provides 20 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
the supplement provides 40 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
the supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
the supplement provides 130 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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latency of visually evoked potentials
Time Frame: assessed basally (before intervention start) and at the end of the 6 month intervention period
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assessed basally (before intervention start) and at the end of the 6 month intervention period
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
fatty acid composition of plasma phospholipids
Time Frame: assessed basally (before intervention start) and at the end of the 6 month intervention period
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assessed basally (before intervention start) and at the end of the 6 month intervention period
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fine motor skills
Time Frame: assessed basally (before intervention start) and at the end of the 6 month intervention period
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assessed basally (before intervention start) and at the end of the 6 month intervention period
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test of reaction time
Time Frame: assessed basally (before intervention start) and at the end of the 6 month intervention period
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assessed basally (before intervention start) and at the end of the 6 month intervention period
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Berthold Koletzko, Prof., Dr. von Hauner Children Hospital, Ludwig-Maximilians-Universitaet Muenchen
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 455-08
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Washington University School of MedicineUniversity of Missouri-Columbia; Northwestern University; Oregon Health and Science... and other collaboratorsTerminated
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University of Southern CaliforniaBioMarin PharmaceuticalCompleted
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