Nutritional Status in Phenylketonuria

NCT03820804 | Completed FDA Drug

• 1 other identifier: Nutrition_PKU
• Study Type: observational
• Target: 94
• Locations: 1 country
• Sites: 1

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. 1.Global nutritional status is not significantly affected in patients with PKU under exclusive dietary treatment.
2. 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. 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).

Conditions

Phenylketonurias

Outcome Measures

Primary Outcomes (2)

• Overweight and obesity prevalence

  To determine the prevalence of overweight and obesity.

  2009-2018

• Overweight and obesity incidence

  To determine the incidence of overweight and obesity.

  2009-2018

Secondary Outcomes (6)

• Metabolic syndrome prevalence

  2009-2018

• Metabolic syndrome incidence

  2009-2018

• Body composition using bioelectrical impedance analysis

  2009-2018

• Metabolic control (blood phenylalanine concentration)

  2009-2018

• Metabolic control (blood phenylalanine concentration) and sapropterin

  2015-2018

Study Arms (2)

Diet-treated

Patients with Phenylketonuria under dietary treatment.

Other: Diet

Sapropterin-treated

Patients with Phenylketonuria under sapropterin treatment.

Drug: Sapropterin

Interventions

Diet OTHER

A specific dietary treatment for patients with Phenylketonuria.

Also known as: Dietary treatment

Diet-treated

Sapropterin DRUG

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

Also known as: Tetrahydrobiopterin

Sapropterin-treated

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universidade do Porto: lead
• Centro Hospitalar do Porto: collaborator
• BioMarin Pharmaceutical: collaborator

Study Sites (1)

Centro Hospitalar Universitário do Porto

Porto, 4099-001, Portugal

Location

Related Publications (8)

• 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.

  PMID: 21944460 BACKGROUND

• 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.

  PMID: 23137570 BACKGROUND

• 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.

  PMID: 21959353 BACKGROUND

• 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.

  PMID: 24055312 BACKGROUND

• 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.

  PMID: 21466737 BACKGROUND

• 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.

  PMID: 24183791 BACKGROUND

• 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.

  PMID: 27896128 BACKGROUND

• 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.

  PMID: 26598928 BACKGROUND

MeSH Terms

Conditions

Phenylketonurias

Interventions

Diet; sapropterin

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Júlio C Rocha, PhD

  Centro Hospitalar do Porto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2018
• First Posted: January 29, 2019
• Study Start: January 7, 2019
• Primary Completion: September 10, 2019
• Study Completion: September 10, 2019
• Last Updated: September 10, 2019

Record last verified: 2018-12

Locations

PT (1)