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

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

Sponsors

Lead Sponsor: Ludwig-Maximilians - University of Munich

Collaborator: European Union

Source Ludwig-Maximilians - University of Munich
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.

Overall Status Completed
Start Date May 2009
Completion Date March 2013
Primary Completion Date July 2011
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
latency of visually evoked potentials assessed basally (before intervention start) and at the end of the 6 month intervention period
Secondary Outcome
Measure Time Frame
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
Enrollment 114
Condition
Intervention

Intervention Type: Dietary Supplement

Intervention Name: high oleic sunflower oil

Description: placebo, which does not provide DHA

Arm Group Label: 1

Intervention Type: Dietary Supplement

Intervention Name: microalgal oil

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

Arm Group Label: 2

Intervention Type: Dietary Supplement

Intervention Name: microalgal oil

Description: the supplement provides 40 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)

Arm Group Label: 3

Intervention Type: Dietary Supplement

Intervention Name: microalgal oil

Description: the supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)

Arm Group Label: 4

Intervention Type: Dietary Supplement

Intervention Name: microalgal oil

Description: the supplement provides 130 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)

Arm Group Label: 5

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

Gender: All

Minimum Age: 5 Years

Maximum Age: 13 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Berthold Koletzko, Prof. Principal Investigator Dr. von Hauner Children Hospital, Ludwig-Maximilians-Universitaet Muenchen
Location
Facility:
Zentrum für Kinder- und Jugendmedizin | Heidelberg, D-69120, Germany
LMU | Muenchen, D-80337, Germany
Department of Pediatrics, San Paolo Hospital Milano | Milano, Italy
Department of Pediatrics, IFIMAV-Hospital M. Valdecill | Santander, Spain
The Childrens Hospital Birmingham | Birmingham, United Kingdom
Department of Pediatrics, Great Ormond Street Hospital for Sick Children | London, United Kingdom
Location Countries

Germany

Italy

Spain

United Kingdom

Verification Date

May 2018

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Ludwig-Maximilians - University of Munich

Investigator Full Name: Prof. Berthold Koletzko

Investigator Title: Prof.

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 5
Arm Group

Label: 1

Type: Placebo Comparator

Label: 2

Type: Experimental

Label: 3

Type: Experimental

Label: 4

Type: Experimental

Label: 5

Type: Experimental

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Basic Science

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov