Clinical trial NCT04251494: A Study Into the Future Cardiovascular Disease (CVD) Risk of Phenylketonuria (PKU) Patients on a Low Phenylalanine Treatment Diet (LPD).
Official title: An Observational, Cross-sectional Study Into the Future Cardiovascular Disease (CVD) Risk of Phenylketonuria (PKU) Patients on a Low Phenylalanine Treatment Diet (LPD).
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Phenylketonurias
Cardiovascular Diseases
Keywords: PKU
CVD
Cardiovascular disease risk
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
First posted: 2020-02-05
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Phenylketonuria patients at Guys and St Thomas' Centre for Inherited Metabolic Diseases, who have a diagnosis of Phenylketonuria at birth (following the introduction of the newborn screening programme), and who are over the age of 18 will be invited to take part in the study.

The population is predominantly caucasian and middle aged.

Brief summary: This study will assess the cardiovascular disease (CVD) risk in Phenylketonuria (PKU) patients on a low-phenylalanine diet (LPD).

Ultrasound tests, diet information and routine blood samples will be collected once per patient at their next outpatient appointment.

32 adults with PKU will be studied and compared to reference data for healthy people. The results will show if the PKU CVD risk differs from healthy people, and if CVD risk varies within people with PKU.

Detailed description: Cardiovascular disease (CVD) is the largest cause of deaths worldwide each year. Many factors affect CVD including diet, genetics, exercise and smoking. It is unclear if Phenylketonuria (PKU) and the low-phenylalanine diet (LPD) affect CVD risk.

CVD risk can be predicted by measuring the thickness of the artery wall in the neck which supplies blood to the head. Thickness is measured using a non-invasive, safe ultrasound test (similar to pregnancy jelly scans). A wall thicker than normal indicates an increased CVD risk. A wall thinner than normal indicates a lower CVD risk.

Eligibility criteria: Inclusion Criteria:

* Phenylketonuria patients at Guys and St Thomas' Centre for Inherited Metabolic Diseases, who have a diagnosis of Phenylketonuria at birth (following the introduction of the newborn screening programme), and who are over the age of 18 will be invited to take part in the study.
* The study will only include patients diagnosed at birth, which will allow a better assessment of the effects of the diet, which are not influenced by a late diagnosis and a prior diet which is not low-Phenylalanine.

Exclusion Criteria:

* Phenylketonuria patients at Guys and St Thomas' Centre for Inherited Metabolic Diseases, who have a diagnosis of Phenylketonuria after birth (not diagnosed during newborn screening), will be excluded from taking part in the study.
* If patients are pregnant, or plan to be pregnant during the study they will also be excluded.
* Patients with a previous history of cardiovascular disease, and/or a history of cardiovascular disease in their immediate family will also be excluded.
* Patients that are unable to understand and consent to the study (i.e. due to language issues or lacking capacity) will also be excluded.

Primary outcomes:
measure: A single carotid-intima media thickness (CIMT) measurement in Phenylketonuria (PKU) participants and the corresponding age- and gender-matched controls.
timeFrame: 10 minutes
Secondary outcomes:
measure: Pulse Wave Velocity (PWV)
timeFrame: 10 minutes
measure: Ankle brachial pressure index (ABPI)
timeFrame: 10 minutes
measure: Vitamin B12 levels from blood sample
timeFrame: 5 minutes
measure: Blood Phenylalanine levels
timeFrame: 5 minutes
measure: Blood low-density lipoprotein (LDL) cholesterol levels
timeFrame: 5 minutes
measure: Diet diary and diet questionnaire (Mediterranean Adherence Screener, 0-14 scale, 14 indicating full adherence, 0 indicating no adherence)
timeFrame: 3 days
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
Study officials:
affiliation: GSTT
name: Radha Ramachandran
role: PRINCIPAL_INVESTIGATOR
References:
citation: Krikke M, Arends JE, Van Lelyveld S, Hoepelman A, Visseren F. Greater carotid intima media thickness at a younger age in HIV-infected patients compared with reference values for an uninfected cohort. HIV Med. 2017 Apr;18(4):275-283. doi: 10.1111/hiv.12428. Epub 2016 Aug 1.
citation: Engelen L, Ferreira I, Stehouwer CD, Boutouyrie P, Laurent S; Reference Values for Arterial Measurements Collaboration. Reference intervals for common carotid intima-media thickness measured with echotracking: relation with risk factors. Eur Heart J. 2013 Aug;34(30):2368-80. doi: 10.1093/eurheartj/ehs380. Epub 2012 Nov 27.
citation: Bots ML, Evans GW, Tegeler CH, Meijer R. Carotid Intima-media Thickness Measurements: Relations with Atherosclerosis, Risk of Cardiovascular Disease and Application in Randomized Controlled Trials. Chin Med J (Engl). 2016 Jan 20;129(2):215-26. doi: 10.4103/0366-6999.173500.
citation: 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.
citation: Htun P, Nee J, Ploeckinger U, Eder K, Geisler T, Gawaz M, Bocksch W, Fateh-Moghadam S. Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation. PLoS One. 2015 Aug 20;10(8):e0135930. doi: 10.1371/journal.pone.0135930. eCollection 2015.