Comparison of Atherogenic Risk Factors and Efficacy of Nutritional Treatment Among Adult Phenylketonuria Patients

NCT04969809 | Not Yet Recruiting DMC

• 1 other identifier: AMezek
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

Phenylketonuria is a rare metabolic disease that results from the absence or near-absence activity of the enzyme phenylalanine hydroxylase, which metabolizes the amino acid phenylalanine to tyrosine in the body. Accumulation of phenylalanine in the brain causes brain damage that leads to mental retardation, neurological complications, and movement disorders. The study is inherited autosomal recessively. The basis of treatment is a low-protein diet with dietary supplements of aminoxlin without phenylalanine and with appropriate substitutes for micro and macronutrients needed for different ages. A low-protein diet regulates the level of phenylalanine in the blood. This is especially important in childhood. In the study, which will basically consist of theoretical, experimental and numerical work, the investigators will limit to a specific population, i.e. to adult patients with phenylketonuria. The research is intended to prove the hypothesis that with proper nutritional treatment of phenylketonuria in adulthood, we can have a positive effect on the patient's well-being, better blood results and improved lifestyle. The investigators intend to test this hypothesis by implementing a complex, multidisciplinary project that will include a comprehensive treatment of adult PKU patients. This will be based on a multidisciplinary approach with the inclusion of medical and nutritional treatment. As part of the project, the investigators, among other things, create questionnaires and analyze food diaries related to the mentioned areas. Using various statistical techniques, the investigators analyze the impact of individual factors on the success of achieving the objectives of the proposed study. The original contribution to science will be the nutritional treatment of adult patients with phenylketonuria in Slovenia and the consequent reduction of health complications in adulthood of patients with phenylketonuria.

Conditions

Phenylketonurias; Nutritional and Metabolic Diseases

Keywords

adult phenylketonuria; nutrition therapy; cardiovascular diseases; nutrition and metabolic diseases

Outcome Measures

Primary Outcomes (2)

• assess the differences between the group of patients with questionnaire

  Use a questionnaire in patients to assess the differences between the group of patients on dietary treatment and the group of patients who discontinued treatment: demographic characteristics (gender, age, education, source of income, marital status), comorbidities or treatments, smoking , sleep disorders, self - assessment of physical activity, self - assessment of health.

  up to 6 months

• Determination of the effectiveness of the dietary intervention of individual nutrition counseling for reduced Phe intake in the blood and the balance of nutrients and elements in the diet

  Phe intake in the blood (µmol/L)

  up to 6 months

Secondary Outcomes (5)

• Comparison of the assessment of risk factors for atherogenesis

  1 day

• Assessment of risk factors for atherogenesis before and after dietary intervention 1

  up to 6 months

• Assessment of risk factors for atherogenesis before and after dietary intervention 2

  up to 6 months

• Assessment of risk factors for atherogenesis before and after dietary intervention 3

  up to 6 months

• Bioelectrical impedance analysis (BIA)

  up to 6 months

Study Arms (2)

Patients on diet

EXPERIMENTAL

We will invite approximately 50 adult patients with PKU who were or are still being managed in the PPB clinic of the Pediatric Clinic of the University Medical Center Ljubljana. It is estimated that half of the patients still fully or at least partially follow the dietary treatment.

Diagnostic Test: Ultrasound of the jugular veins; Dietary Supplement: addition of phenylalanine-free protein substitutes

patients without diet

EXPERIMENTAL

Half of the patients have abandoned the diet treatment and mostly no longer come for outpatient examinations.

Diagnostic Test: Ultrasound of the jugular veins; Dietary Supplement: addition of phenylalanine-free protein substitutes

Interventions

Ultrasound of the jugular veins DIAGNOSTIC_TEST

Ultrasound of the jugular veins to assess the thickness of the carotid intima media

Patients on diet; patients without diet

addition of phenylalanine-free protein substitutes DIETARY_SUPPLEMENT

addition of phenylalanine-free protein substitutes for sufficient daily intake of essential amino acids and other vitamins and minerals and nutritional plan

Patients on diet; patients without diet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The study will include subjects over the age of 18 who have PKU or hyperphenylalaninemia and are expected to have dietary treatment according to expert recommendations. A prerequisite for entering the investigation will be a signed consent to participate in the investigation and the ability of the participant to have a good understanding of the content of the research and to fully participate in the interventional dietary process.

You may not qualify if:

• The investigators will not include adult patients who do not manage their diet on their own and need caregivers due to limited cognitive abilities (patients with late-diagnosed disease and neurological consequences of the disease) or who do not want to sign an informed consent.

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Related Publications (21)

• Azabdaftari A, van der Giet M, Schuchardt M, Hennermann JB, Plockinger U, Querfeld U. The cardiovascular phenotype of adult patients with phenylketonuria. Orphanet J Rare Dis. 2019 Sep 6;14(1):213. doi: 10.1186/s13023-019-1188-0.

  PMID: 31492166 BACKGROUND

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• Burton BK, Jones KB, Cederbaum S, Rohr F, Waisbren S, Irwin DE, Kim G, Lilienstein J, Alvarez I, Jurecki E, Levy H. Prevalence of comorbid conditions among adult patients diagnosed with phenylketonuria. Mol Genet Metab. 2018 Nov;125(3):228-234. doi: 10.1016/j.ymgme.2018.09.006. Epub 2018 Sep 12.

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• Cazzorla C, Bensi G, Biasucci G, Leuzzi V, Manti F, Musumeci A, Papadia F, Stoppioni V, Tummolo A, Vendemiale M, Polo G, Burlina A. Living with phenylketonuria in adulthood: The PKU ATTITUDE study. Mol Genet Metab Rep. 2018 Jul 11;16:39-45. doi: 10.1016/j.ymgmr.2018.06.007. eCollection 2018 Sep.

  PMID: 30069431 BACKGROUND

• Das AM, Goedecke K, Meyer U, Kanzelmeyer N, Koch S, Illsinger S, Lucke T, Hartmann H, Lange K, Lanfermann H, Hoy L, Ding XQ. Dietary habits and metabolic control in adolescents and young adults with phenylketonuria: self-imposed protein restriction may be harmful. JIMD Rep. 2014;13:149-58. doi: 10.1007/8904_2013_273. Epub 2013 Nov 13.

  PMID: 24222493 BACKGROUND

• Ford S, O'Driscoll M, MacDonald A. Living with Phenylketonuria: Lessons from the PKU community. Mol Genet Metab Rep. 2018 Oct 18;17:57-63. doi: 10.1016/j.ymgmr.2018.10.002. eCollection 2018 Dec.

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• Green B, Browne R, Firman S, Hill M, Rahman Y, Kaalund Hansen K, Adam S, Skeath R, Hallam P, Herlihy I, Jenkinson F, Nicol C, Adams S, Gaff L, Donald S, Dawson C, Robertson L, Fitzachary C, Chan H, Slabbert A, Dunlop C, Cozens A, Newby C, Bittle V, Hubbard G, Stratton R. Nutritional and Metabolic Characteristics of UK Adult Phenylketonuria Patients with Varying Dietary Adherence. Nutrients. 2019 Oct 14;11(10):2459. doi: 10.3390/nu11102459.

  PMID: 31615158 BACKGROUND

• Hansen KE, Ney D. A systematic review of bone mineral density and fractures in phenylketonuria. J Inherit Metab Dis. 2014 Nov;37(6):875-80. doi: 10.1007/s10545-014-9735-2. Epub 2014 Jul 9.

  PMID: 25005329 BACKGROUND

• Hermida-Ameijeiras A, Crujeiras V, Roca I, Calvo C, Leis R, Couce ML. Arterial stiffness assessment in patients with phenylketonuria. Medicine (Baltimore). 2017 Dec;96(51):e9322. doi: 10.1097/MD.0000000000009322.

  PMID: 29390507 BACKGROUND

• MacDonald A, Gokmen-Ozel H, van Rijn M, Burgard P. The reality of dietary compliance in the management of phenylketonuria. J Inherit Metab Dis. 2010 Dec;33(6):665-70. doi: 10.1007/s10545-010-9073-y. Epub 2010 Apr 7.

  PMID: 20373144 BACKGROUND

• MacLeod EL, Gleason ST, van Calcar SC, Ney DM. Reassessment of phenylalanine tolerance in adults with phenylketonuria is needed as body mass changes. Mol Genet Metab. 2009 Dec;98(4):331-7. doi: 10.1016/j.ymgme.2009.07.016. Epub 2009 Aug 8.

  PMID: 19747868 BACKGROUND

• Okano Y, Hattori T, Fujimoto H, Noi K, Okamoto M, Watanabe T, Watanabe R, Fujii R, Tamaoki T. Nutritional status of patients with phenylketonuria in Japan. Mol Genet Metab Rep. 2016 Aug 20;8:103-10. doi: 10.1016/j.ymgmr.2016.08.005. eCollection 2016 Sep.

  PMID: 27595068 BACKGROUND

• Robertson LV, McStravick N, Ripley S, Weetch E, Donald S, Adam S, Micciche A, Boocock S, MacDonald A. Body mass index in adult patients with diet-treated phenylketonuria. J Hum Nutr Diet. 2013 Jul;26 Suppl 1:1-6. doi: 10.1111/jhn.12054. Epub 2013 Apr 3.

  PMID: 23551621 BACKGROUND

• Rocha JC, MacDonald A. Dietary intervention in the management of phenylketonuria: current perspectives. Pediatric Health Med Ther. 2016 Dec 1;7:155-163. doi: 10.2147/PHMT.S49329. eCollection 2016.

  PMID: 29388626 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

• Smon A, Groselj U, Zerjav Tansek M, Bicek A, Oblak A, Zupancic M, Krzisnik C, Repic Lampr Et B, Murko S, Hojker S, Battelino T. Newborn Screening in Slovenia. Zdr Varst. 2015 Mar 13;54(2):86-90. doi: 10.1515/sjph-2015-0013. eCollection 2015 Jun.

  PMID: 27646913 BACKGROUND

• ten Hoedt AE, de Sonneville LM, Francois B, ter Horst NM, Janssen MC, Rubio-Gozalbo ME, Wijburg FA, Hollak CE, Bosch AM. High phenylalanine levels directly affect mood and sustained attention in adults with phenylketonuria: a randomised, double-blind, placebo-controlled, crossover trial. J Inherit Metab Dis. 2011 Feb;34(1):165-71. doi: 10.1007/s10545-010-9253-9. Epub 2010 Dec 10.

  PMID: 21153445 BACKGROUND

• Vockley J, Andersson HC, Antshel KM, Braverman NE, Burton BK, Frazier DM, Mitchell J, Smith WE, Thompson BH, Berry SA; American College of Medical Genetics and Genomics Therapeutics Committee. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med. 2014 Feb;16(2):188-200. doi: 10.1038/gim.2013.157. Epub 2013 Oct 10.

  PMID: 24385074 BACKGROUND

• van Spronsen FJ, van Wegberg AM, Ahring K, Belanger-Quintana A, Blau N, Bosch AM, Burlina A, Campistol J, Feillet F, Gizewska M, Huijbregts SC, Kearney S, Leuzzi V, Maillot F, Muntau AC, Trefz FK, van Rijn M, Walter JH, MacDonald A. Key European guidelines for the diagnosis and management of patients with phenylketonuria. Lancet Diabetes Endocrinol. 2017 Sep;5(9):743-756. doi: 10.1016/S2213-8587(16)30320-5. Epub 2017 Jan 10.

  PMID: 28082082 BACKGROUND

• van Wegberg AMJ, MacDonald A, Ahring K, Belanger-Quintana A, Blau N, Bosch AM, Burlina A, Campistol J, Feillet F, Gizewska M, Huijbregts SC, Kearney S, Leuzzi V, Maillot F, Muntau AC, van Rijn M, Trefz F, Walter JH, van Spronsen FJ. The complete European guidelines on phenylketonuria: diagnosis and treatment. Orphanet J Rare Dis. 2017 Oct 12;12(1):162. doi: 10.1186/s13023-017-0685-2.

  PMID: 29025426 BACKGROUND

• Verduci E, Carbone MT, Borghi E, Ottaviano E, Burlina A, Biasucci G. Nutrition, Microbiota and Role of Gut-Brain Axis in Subjects with Phenylketonuria (PKU): A Review. Nutrients. 2020 Oct 29;12(11):3319. doi: 10.3390/nu12113319.

  PMID: 33138040 BACKGROUND

MeSH Terms

Conditions

Phenylketonurias; Nutritional and Metabolic Diseases; Cardiovascular Diseases; Metabolic Diseases

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

Central Study Contacts

Ajda Mezek, master

CONTACT

0038640656109; ajda.mezek@gmail.com

Mojca Žerjav Tanšek, doctorate

CONTACT

mojca.zerjav-tansek@mf.uni-lj.si

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: mag.diet.

Model Details: We will invite approximately 50 adult patients with PKU who were or are still being managed in the PPB clinic of the Pediatric Clinic of the University Medical Center Ljubljana. It is estimated that half of the patients still fully or at least partially follow the dietary treatment, while half have abandoned the treatment and mostly no longer come for outpatient examinations.

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: July 21, 2021
• Study Start: September 1, 2021
• Primary Completion: September 1, 2026
• Study Completion: September 1, 2026
• Last Updated: July 21, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share