PhenylketonuriaNCT00909012
Quantitative Requirements of Docosahexaenoic Acid for Neural Function in Children With Phenylketonuria
A study testing high oleic sunflower oil and microalgal oil in people with Phenylketonuria, run by Ludwig-Maximilians - University of Munich at 6 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 13 years
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- high oleic sunflower oil and microalgal oil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 114 participants
- Where
- 6 sitesin 4 countries
- Study dates
- May 2009to Mar 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 13 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
Germany2 sites
Zentrum für Kinder- und Jugendmedizin
Heidelberg, D-69120
LMU
München, D-80337
United Kingdom2 sites
The Childrens Hospital Birmingham
Birmingham
Department of Pediatrics, Great Ormond Street Hospital for Sick Children
London
About this study
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
- Being tested
- high oleic sunflower oil, microalgal oil
- Keywords
- phenylketonuria, docosahexaenoic acid, visually evoked potential, choice-reaction time
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
high oleic sunflower oilDietary supplement
placebo, which does not provide DHA
microalgal oilDietary supplement
the supplement provides 20 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
microalgal oilDietary supplement
the supplement provides 40 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
microalgal oilDietary supplement
the supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
microalgal oilDietary supplement
the supplement provides 130 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Not described Receives: Dietary Supplement: high oleic sunflower oil |
| 2 | Experimental | Not described Receives: Dietary Supplement: microalgal oil |
| 3 | Experimental | Not described Receives: Dietary Supplement: microalgal oil |
| 4 | Experimental | Not described Receives: Dietary Supplement: microalgal oil |
| 5 | Experimental | Not described Receives: Dietary Supplement: microalgal oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
latency of visually evoked potentials
Measured: assessed basally (before intervention start) and at the end of the 6 month intervention period
Secondary outcomes (3)
fatty acid composition of plasma phospholipids
Measured: assessed basally (before intervention start) and at the end of the 6 month intervention period
fine motor skills
Measured: assessed basally (before intervention start) and at the end of the 6 month intervention period
test of reaction time
Measured: assessed basally (before intervention start) and at the end of the 6 month intervention period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2009 (estimated)
- Study startMay 2009
- Primary completionJul 2011
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig-Maximilians - University of Munich
- Sponsor type
- University, hospital or other
- Collaborators
- European Union
- Responsible party
- Principal investigator, Prof. Berthold Koletzko, Ludwig-Maximilians - University of Munich
- Investigators
- Berthold Koletzko, Prof., Principal investigator, Dr. von Hauner Children Hospital, Ludwig-Maximilians-Universitaet Muenchen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00909012
- Sponsor's protocol ID
- 455-08
- Status last verified
- Aug 2022
- First submitted
- 22 Apr 2009
- Last updated
- 22 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30544518
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantitative Requirements of Docosahexaenoic Acid for Neural Function in Children With Phenylketonuria
- ClinicalTrials.gov ID
- NCT00909012
- Acronym / sponsor ID
- 455-08
- Conditions
- Phenylketonuria
- Keywords
- phenylketonuria, docosahexaenoic acid, visually evoked potential, choice-reaction time
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Ludwig-Maximilians - University of MunichUniversity, hospital or other
- Collaborators
- European Union
- Study start
- May 2009
- Primary completion
- Jul 2011 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 27 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 5 to 13 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| high oleic sunflower oilplacebo, which does not provide DHA | Dietary supplement | 1 |
| microalgal oilthe supplement provides 20 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight) | Dietary supplement | 2 |
| microalgal oilthe supplement provides 40 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight) | Dietary supplement | 3 |
| microalgal oilthe supplement provides 80 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight) | Dietary supplement | 4 |
| microalgal oilthe supplement provides 130 mg DHA per capsule (1 or 2 are consumed per day, depending on body weight) | Dietary supplement | 5 |
Primary outcome
latency of visually evoked potentials
Time frame: assessed basally (before intervention start) and at the end of the 6 month intervention period
3 secondary outcomes
fatty acid composition of plasma phospholipids
Time frame: 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
test of reaction time
Time frame: assessed basally (before intervention start) and at the end of the 6 month intervention period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2022.
- Results publication: PubMed 30544518Demmelmair 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Berthold Koletzko, Prof. principal investigator
Dr. von Hauner Children Hospital, Ludwig-Maximilians-Universitaet Muenchen
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing high oleic sunflower oil and microalgal oil in people with Phenylketonuria, run by Ludwig-Maximilians - University of Munich at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany, United Kingdom, Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
latency of visually evoked potentials (time frame: assessed basally (before intervention start) and at the end of the 6 month intervention period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00909012, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2022.