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

August 18, 2022 updated by: Prof. Berthold Koletzko, Ludwig-Maximilians - University of Munich

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
114

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Heidelberg, Germany, D-69120
        • Zentrum für Kinder- und Jugendmedizin
      • Muenchen, Germany, D-80337
        • LMU
  • Italy
      • Milano, Italy
        • Department of Pediatrics, San Paolo Hospital Milano
  • Spain
      • Santander, Spain
        • Department of Pediatrics, IFIMAV-Hospital M. Valdecill
  • United Kingdom
      • Birmingham, United Kingdom
        • The Childrens Hospital Birmingham
      • London, United Kingdom
        • Department of Pediatrics, Great Ormond Street Hospital for Sick Children

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

5 years to 13 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 2
Dietary supplement: microalgal oil
the supplement provides 20 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Dietary supplement: microalgal oil
the supplement provides 40 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Dietary supplement: microalgal oil
the supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Dietary supplement: microalgal oil
the supplement provides 130 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Placebo Comparator: 1
Dietary supplement: high oleic sunflower oil
placebo, which does not provide DHA
Experimental: 3
Dietary supplement: microalgal oil
the supplement provides 20 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Dietary supplement: microalgal oil
the supplement provides 40 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Dietary supplement: microalgal oil
the supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Dietary supplement: microalgal oil
the supplement provides 130 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Experimental: 4
Dietary supplement: microalgal oil
the supplement provides 20 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Dietary supplement: microalgal oil
the supplement provides 40 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Dietary supplement: microalgal oil
the supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Dietary supplement: microalgal oil
the supplement provides 130 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Experimental: 5
Dietary supplement: microalgal oil
the supplement provides 20 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Dietary supplement: microalgal oil
the supplement provides 40 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Dietary supplement: microalgal oil
the supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
Dietary supplement: microalgal oil
the supplement provides 130 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
latency of visually evoked potentials
Time Frame: assessed basally (before intervention start) and at the end of the 6 month intervention period
assessed basally (before intervention start) and at the end of the 6 month intervention period

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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
assessed basally (before intervention start) and at the end of the 6 month intervention period
fine motor skills
Time Frame: assessed basally (before intervention start) and at the end of the 6 month intervention period
assessed basally (before intervention start) and at the end of the 6 month intervention period
test of reaction time
Time Frame: assessed basally (before intervention start) and at the end of the 6 month intervention period
assessed basally (before intervention start) and at the end of the 6 month intervention period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ludwig-Maximilians - University of Munich

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
European Union

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Berthold Koletzko, Prof., Dr. von Hauner Children Hospital, Ludwig-Maximilians-Universitaet Muenchen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 22, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 26, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 27, 2009

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 22, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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