Nutritional Status in Phenylketonuria

NCT ID: NCT03820804

Last Updated: 2019-09-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

94 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-01-07

Study Completion Date

2019-09-10

Brief Summary

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In the era of Phenylketonuria (PKU) newborn screening, early diagnosis in the neonatal period and prompt treatment institution has protected patients from developing severe and irreversible mental retardation. The main objective of the treatment is to prevent a chronic elevation of blood Phe concentrations, which together with reduced tyrosine concentrations may increase the risk of neurologic damage. In order to achieve this purpose, the mainstay of treatment is a special diet characterized by a natural protein restriction, supplemented with protein substitutes and special low protein foods.

The requirement to optimize growth and body composition, usually result in dietary prescriptions that are high in carbohydrate (\>60% of energy intake), to promote anabolism, considering the synthetic properties of this special diet. Some studies have described a high risk of developing overweight and obesity. Although there is a tendency for a higher incidence in females, it seems that the prevalence in PKU patients follows the same trend as the general population. However, there are limited studies published so far and no longitudinal studies are available describing current practice and its impact on the prevalence of overweight and obesity; neither its consequences in terms of metabolic syndrome or cardiometabolic markers.

Recently, sapropterin dihydrochloride, which is the synthetic form of Phenylalanine Hydroxylase cofactor, is available in Portugal for patients with PKU. In practice, the sapropterin treated patients increase their natural protein intake, minimizing the synthetic characteristics of the diet. While there is a need for patient re-education about the practicalities of meeting their nutritional needs, scientific evidence about the nutritional status impact of diet liberalization is inadequate.

This study aims to test the following hypothesis:

1. Global nutritional status is not significantly affected in patients with PKU under exclusive dietary treatment.
2. There is a trend for increased rates of overweight and obesity in patients with PKU from 2009 and we consider this will continue to increase.
3. The start of sapropterin treatment allows a higher natural protein intake in patients with PKU that significantly targets nutritional status in at least one of its components (anthropometry, body composition or biochemistry).

Detailed Description

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At the Centro Hospitalar do Porto (Reference Centre for the treatment of Inherited Metabolic Diseases) the annual nutritional status evaluation routinely generates data on anthropometry, body composition, blood pressure, nutritional intake and clinical biochemistry. Since 2009, all this information is recorded for all the patients with PKU under follow-up.

For the purpose of this project, data will be collected, from 2009 until 2018, using a minimum of 5 annual nutritional status evaluations per patient. The project will be able to compare the longitudinal evolution of nutritional status in exclusively diet treated patients (period between 2009 and 2014) with a subgroup of patients already under sapropterin treatment in the period between 2015 and 2018. Genotype is available for all patients with PKU under follow-up at Centro Hospitalar do Porto. However, the decision for starting sapropterin treatment was based on the results from a sapropterin-loading test protocol, approved in 2014 by the Portuguese Society of Metabolic Disorders (not published).

For every PKU patient under follow-up at Centro Hospitalar do Porto, the information about nutritional intake is recorded in a special file that contains all the diet details collected in every appointment. In that way, for the purpose of the annual nutritional status evaluation, every PKU patient is submitted to anthropometric and body composition evaluations, blood pressure assessment and blood samples collection for completing the hematological and biochemical measurements. Also in the same day, at the nutrition appointment, a dietary assessment is done, in order to allow further nutrition adjustments when needed. This approach allows us to know the precise nutritional ingestion in the period before all the measurements.

Data will be collected from patient databases or patient records. In the period between 2009 and 2014 there are no treatments or interventions to which the patients can be randomly assigned, as no specific treatment is the focus of the project. In the period between 2015 and 2018, patients will be divided in two groups based on treatment modalities: diet-treated only or sapropterin treatment. However, their assignment in each group does not have any influence of the project itself. The inclusion in one of the two groups will be decided based on the results of the sapropterin loading test done previously within the clinical routine protocol. Patients will be identified only by a number and only medical data will be collected. No directly or indirectly nominative data will be collected and data will be anonymous.

Conditions

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Phenylketonurias

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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Diet-treated

Patients with Phenylketonuria under dietary treatment.

Diet

Intervention Type OTHER

A specific dietary treatment for patients with Phenylketonuria.

Sapropterin-treated

Patients with Phenylketonuria under sapropterin treatment.

Sapropterin

Intervention Type DRUG

A pharmacological treatment for patients with Phenylketonuria, used alone or in combination with dietary treatment.

Interventions

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Diet

A specific dietary treatment for patients with Phenylketonuria.

Intervention Type OTHER

Sapropterin

A pharmacological treatment for patients with Phenylketonuria, used alone or in combination with dietary treatment.

Intervention Type DRUG

Other Intervention Names

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Dietary treatment Tetrahydrobiopterin

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of PKU.
* With all the clinical data available since 2009.
* Have completed the annual routine nutritional status evaluation in the periods 2009/2010, 2011/2012, 2013/2014, 2015/2016 and 2017/2018.
* Maintaining a follow-up at Centro Hospitalar do Porto.

Exclusion Criteria

* Lost of follow-up.
* Not have completed at least one full evaluation in each time period: 2009/2010, 2011/2012, 2013/2014, 2015/2016 and 2017/2018.
* Any other chronic medical condition which may affect diet or nutritional status.
Minimum Eligible Age

3 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centro Hospitalar do Porto

OTHER

Sponsor Role collaborator

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role collaborator

Universidade do Porto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Júlio C Rocha, PhD

Role: PRINCIPAL_INVESTIGATOR

Centro Hospitalar do Porto

Locations

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Centro Hospitalar Universitário do Porto

Porto, , Portugal

Site Status

Countries

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Portugal

References

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MacDonald A, Rocha JC, van Rijn M, Feillet F. Nutrition in phenylketonuria. Mol Genet Metab. 2011;104 Suppl:S10-8. doi: 10.1016/j.ymgme.2011.08.023. Epub 2011 Sep 2.

Reference Type BACKGROUND
PMID: 21944460 (View on PubMed)

Rocha JC, van Spronsen FJ, Almeida MF, Soares G, Quelhas D, Ramos E, Guimaraes JT, Borges N. Dietary treatment in phenylketonuria does not lead to increased risk of obesity or metabolic syndrome. Mol Genet Metab. 2012 Dec;107(4):659-63. doi: 10.1016/j.ymgme.2012.10.006. Epub 2012 Oct 16.

Reference Type BACKGROUND
PMID: 23137570 (View on PubMed)

Dokoupil K, Gokmen-Ozel H, Lammardo AM, Motzfeldt K, Robert M, Rocha JC, van Rijn M, Ahring K, Belanger-Quintana A, MacDonald A. Optimising growth in phenylketonuria: current state of the clinical evidence base. Clin Nutr. 2012 Feb;31(1):16-21. doi: 10.1016/j.clnu.2011.09.001. Epub 2011 Sep 29.

Reference Type BACKGROUND
PMID: 21959353 (View on PubMed)

Rocha JC, MacDonald A, Trefz F. Is overweight an issue in phenylketonuria? Mol Genet Metab. 2013;110 Suppl:S18-24. doi: 10.1016/j.ymgme.2013.08.012. Epub 2013 Aug 31.

Reference Type BACKGROUND
PMID: 24055312 (View on PubMed)

MacDonald A, Ahring K, Dokoupil K, Gokmen-Ozel H, Lammardo AM, Motzfeldt K, Robert M, Rocha JC, van Rijn M, Belanger-Quintana A. Adjusting diet with sapropterin in phenylketonuria: what factors should be considered? Br J Nutr. 2011 Jul;106(2):175-82. doi: 10.1017/S0007114511000298.

Reference Type BACKGROUND
PMID: 21466737 (View on PubMed)

Rocha JC, van Spronsen FJ, Almeida MF, Ramos E, Guimaraes JT, Borges N. Early dietary treated patients with phenylketonuria can achieve normal growth and body composition. Mol Genet Metab. 2013;110 Suppl:S40-3. doi: 10.1016/j.ymgme.2013.10.009. Epub 2013 Oct 22.

Reference Type BACKGROUND
PMID: 24183791 (View on PubMed)

Gokmen Ozel H, Ahring K, Belanger-Quintana A, Dokoupil K, Lammardo AM, Robert M, Rocha JC, Almeida MF, van Rijn M, MacDonald A. Overweight and obesity in PKU: The results from 8 centres in Europe and Turkey. Mol Genet Metab Rep. 2014 Nov 16;1:483-486. doi: 10.1016/j.ymgmr.2014.11.003. eCollection 2014.

Reference Type BACKGROUND
PMID: 27896128 (View on PubMed)

Rocha JC, van Rijn M, van Dam E, Ahring K, Belanger-Quintana A, Dokoupil K, Gokmen Ozel H, Lammardo AM, Robert M, Heidenborg C, MacDonald A. Weight Management in Phenylketonuria: What Should Be Monitored. Ann Nutr Metab. 2016;68(1):60-5. doi: 10.1159/000442304. Epub 2015 Nov 25.

Reference Type BACKGROUND
PMID: 26598928 (View on PubMed)

Other Identifiers

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Nutrition_PKU

Identifier Type: -

Identifier Source: org_study_id

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