A Study Into the Future Cardiovascular Disease (CVD) Risk of Phenylketonuria (PKU) Patients on a Low Phenylalanine Treatment Diet (LPD).

Guy's and St Thomas' NHS Foundation Trust

Status: Unknown

Conditions: Phenylketonurias; Cardiovascular Diseases

Treatments: Diagnostic Test: Carotid intima media thickness measurement (CIMT); Other: Routine blood samples; Other: Diet questionnaire and diet diary; Diagnostic Test: Ankle-brachial pressure index (ABPI); Diagnostic Test: Pulse Wave Velocity measurement

Study type: Observational

Funder types: Other

Identifiers

NCT04251494

254922

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

32 participants in 2 patient groups

Phenylketonuria (PKU) participants

Description:

During their outpatient clinic appointment, participants will: * Undergo routine height and weight measurements and blood tests. A full patient history will be taken, including a record of cardiovascular disease within the family. Blood samples will be collected, including phenylalanine, lipids, vitamin B12 and related biomarkers. * Complete a 14-item diet history questionnaire, and fill in a 3 day diet diary before they arrive at their outpatient clinic appointment, which will be collected after the participant signs the informed written consent form. * Undergo assessment of carotid Intima-media thickness (CIMT), pulse wave velocity (PWV), ankle brachial pressure index (ABPI) and systolic and diastolic blood pressure.

Treatment:

Other: Diet questionnaire and diet diary

Diagnostic Test: Ankle-brachial pressure index (ABPI)

Diagnostic Test: Pulse Wave Velocity measurement

Other: Routine blood samples

Diagnostic Test: Carotid intima media thickness measurement (CIMT)

Age and gender matched reference controls

Description:

Only Phenylketonuria (PKU) patients will be studied. Controls are generated from the literature. Reference CIMT values exist for a healthy population based on age and gender (Engelen et al., 2013), eliminating the need to assess age- and gender-matched controls. The study would otherwise require performing blood tests and vascular assessments on healthy individuals, generating a risk of harm and a possible incidental finding. It would be inconvenient for controls because they would need to travel to hospital and undergo invasive venepuncture.