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

Conditions
Phenylketonurias
Cardiovascular Diseases
Interventions
Diagnostic Test: Carotid intima media thickness measurement (CIMT)
Diagnostic Test: Pulse Wave Velocity measurement
Diagnostic Test: Ankle-brachial pressure index (ABPI)
Other: Diet questionnaire and diet diary
Other: Routine blood samples
Registration Number
NCT04251494
Lead Sponsor
Guy's and St Thomas' NHS Foundation Trust
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
32
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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Phenylketonuria (PKU) participantsCarotid intima media thickness measurement (CIMT)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.
Phenylketonuria (PKU) participantsPulse Wave Velocity measurementDuring 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.
Phenylketonuria (PKU) participantsAnkle-brachial pressure index (ABPI)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.
Phenylketonuria (PKU) participantsDiet questionnaire and diet diaryDuring 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.
Phenylketonuria (PKU) participantsRoutine blood samplesDuring 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.
Primary Outcome Measures
NameTimeMethod
A single carotid-intima media thickness (CIMT) measurement in Phenylketonuria (PKU) participants and the corresponding age- and gender-matched controls.10 minutes

A single CIMT measurement in PKU participants at their most recent outpatient appointment, and the corresponding age- and gender-matched CIMT, generated from the male (1) or female (2) equation for a healthy population using each participants' age and gender (Engelen et al., 2013).

Secondary Outcome Measures
NameTimeMethod
Pulse Wave Velocity (PWV)10 minutes

will be compared to PKU patient biomarkers (median annual Phenylalanine levels, biomarkers and dietary factors) to assess if there is any correlation between compliance to diet and variation in cardiovascular risk within PKU patients.

Ankle brachial pressure index (ABPI)10 minutes

will be compared to PKU patient biomarkers (median annual Phe levels, biomarkers and dietary factors) to assess if there is any correlation between compliance to diet and variation in cardiovascular risk within PKU patients.

Vitamin B12 levels from blood sample5 minutes

will be compared to PKU patient measures (PWV, ABPI and CIMT) to assess if there is any correlation between compliance to diet and variation in cardiovascular risk within PKU patients.

Blood Phenylalanine levels5 minutes

will be compared to PKU patient measures (PWV, ABPI and CIMT) to assess if there is any correlation between compliance to diet and variation in cardiovascular risk within PKU patients.

Blood low-density lipoprotein (LDL) cholesterol levels5 minutes

will be compared to PKU patient measures (PWV, ABPI and CIMT) to assess if there is any correlation between compliance to diet and variation in cardiovascular risk within PKU patients.

Diet diary and diet questionnaire (Mediterranean Adherence Screener, 0-14 scale, 14 indicating full adherence, 0 indicating no adherence)3 days

will be compared to PKU patient measures (PWV, ABPI and CIMT) to assess if there is any correlation between compliance to diet and variation in cardiovascular risk within PKU patients.

Trial Locations

Locations (1)

Guy's and St Thomas' NHS Foundation Trust

🇬🇧

London, United Kingdom

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