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Nutritional Status in Phenylketonuria (TNSPKU)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03820804
Recruitment Status : Completed
First Posted : January 29, 2019
Last Update Posted : September 10, 2019
Centro Hospitalar do Porto
BioMarin Pharmaceutical
Information provided by (Responsible Party):
Universidade do Porto

Brief Summary:

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).

Condition or disease Intervention/treatment
Phenylketonurias Other: Diet Drug: Sapropterin

Detailed Description:

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.

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Study Type : Observational
Actual Enrollment : 94 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Trends in Nutritional Status of Patients With Phenylketonuria
Actual Study Start Date : January 7, 2019
Actual Primary Completion Date : September 10, 2019
Actual Study Completion Date : September 10, 2019

Group/Cohort Intervention/treatment
Patients with Phenylketonuria under dietary treatment.
Other: Diet
A specific dietary treatment for patients with Phenylketonuria.
Other Name: Dietary treatment

Patients with Phenylketonuria under sapropterin treatment.
Drug: Sapropterin
A pharmacological treatment for patients with Phenylketonuria, used alone or in combination with dietary treatment.
Other Name: Tetrahydrobiopterin

Primary Outcome Measures :
  1. Overweight and obesity prevalence [ Time Frame: 2009-2018 ]
    To determine the prevalence of overweight and obesity.

  2. Overweight and obesity incidence [ Time Frame: 2009-2018 ]
    To determine the incidence of overweight and obesity.

Secondary Outcome Measures :
  1. Metabolic syndrome prevalence [ Time Frame: 2009-2018 ]
    To determine the change of the prevalence of metabolic syndrome in patients.

  2. Metabolic syndrome incidence [ Time Frame: 2009-2018 ]
    To determine the incidence of metabolic syndrome in patients.

  3. Body composition using bioelectrical impedance analysis [ Time Frame: 2009-2018 ]
    To describe the body composition evolution (fat mass, fat-free mass and phase angle) throughout the 10 years of the study.

  4. Metabolic control (blood phenylalanine concentration) [ Time Frame: 2009-2018 ]
    To describe the evolution of metabolic control in patients.

  5. Metabolic control (blood phenylalanine concentration) and sapropterin [ Time Frame: 2015-2018 ]
    To describe the evolution of metabolic control (blood phenylalanine concentrations) in patients under sapropterin treatment during the period between 2015 and 2018.

  6. Phenylalanine intake and sapropterin [ Time Frame: 2015-2018 ]
    To understand the impact of sapropterin treatment on phenylalanine intake (mg of phenylalanine/day) during the period between 2015 and 2018.

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Centro Hospitalar do Porto is one Portuguese Reference Centre for the treatment of inborn errors of metabolism. A cohort of patients with Phenylketonuria is under follow-up with different treatment strategies implemented. All treatment strategies are fully reimbursed by the Portuguese health system and this project aims to evaluate the longitudinal impact of different treatment options on nutritional status outcome.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03820804

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Centro Hospitalar Universitário do Porto
Porto, Portugal, 4099-001
Sponsors and Collaborators
Universidade do Porto
Centro Hospitalar do Porto
BioMarin Pharmaceutical
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Principal Investigator: Júlio C Rocha, PhD Centro Hospitalar do Porto

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Responsible Party: Universidade do Porto Identifier: NCT03820804    
Other Study ID Numbers: Nutrition_PKU
First Posted: January 29, 2019    Key Record Dates
Last Update Posted: September 10, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: A detailed list of the variables to be collected can be shared with other researchers.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases