Impact of Fruit and Vegetables in PKU

Impact of Fruits and Vegetables on Metabolic Control in Children With PKU

In the UK, some fruits and vegetables are permitted without measurement in the diets of people with phenylketonuria (PKU). It is proven that fruits and vegetables containing phenylalanine (Phe) up to 75mg/100g (e.g. carrots, sweet potato, tomatoes) do not affect blood Phe control but it is unknown to what extent fruits and vegetables containing Phe from 76-100mg/100g (e.g. cauliflower, broccoli, beansprouts and asparagus) increase blood Phe levels. In addition, there is very little information about how differently animal and vegetable protein affect blood Phe levels. It is believed that plant protein may have less bioavailability and therefore have less impact on blood Phe control. The investigators aim is to perform a randomized controlled study over 21 weeks in children (5-12y) with PKU. Children will be studied during five different time periods, examining the effect on blood Phe control when increasing Phe intake from vegetables/fruits containing Phe from 76-100 mg/100g vs. animal sources. At the end of the study, fruits and vegetables containing 76- 100mg Phe/100g will continue to be given as "exchange-free" for 6 months. This is a practical, cost effective study and should bring benefit to all people with PKU following a very restrictive diet both within the UK and throughout the world.

Study Overview

• Status: Completed
• Conditions: Phenylketonurias
• Intervention / Treatment: Other: Phase B - Extra 1 Phe exchange from fruits/vegetables containing Phe from 76-100mg/100g; Other: Phase C - Extra 2 Phe exchanges from fruits/vegetables containing Phe from 76-100mg/100g; Other: Phase D - Extra 1 Phe exchange from milk or yoghurt; Other: Phase E - Extra 2 Phe exchanges from milk or yoghurt

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B4 6NH
      • Birmingham Women's and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• PKU patients diagnosed by NBS and BH4 deficiencies;
• Early and continuously treated;
• Adherent to their prescribed PKU diet consisting of a protein-restricted diet and Phe-free amino acid based protein substitute;
• In good general health as evidenced by medical history;
• Able to provide written informed consent/assent (parent/child);
• Able to comply with the study protocol and take study product according to the opinion of the PI;
• Patients with good metabolic control (age 5-12y, 120-360μmol/L) with 3 out of 4 levels within range prior to consent (if 2 of 4 above target range but one close to the upper limit, PI to decide if patient can enter the study).

Exclusion Criteria:

• Concomitant diseases / disorders such as renal or gut disease / disorders and diabetes;
• Dislikes fruits and vegetables containing 76-100 mg of Phe/100g e.g.brocolli or cauliflower;
• Treated with BH4 (sapropterin);
• Presence of intercurrent infection;
• Patients with poor metabolic control (age 5-12y, >360μmol/L).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group starting intervention with vegetable protein; Phase A followed by Phases B, C, D, E.	Other: Phase B - Extra 1 Phe exchange from fruits/vegetables containing Phe from 76-100mg/100g; Usual low Phe diet + 60g fruits/vegetables containing Phe from 76-100mg/100g; Other: Phase C - Extra 2 Phe exchanges from fruits/vegetables containing Phe from 76-100mg/100g; Usual low Phe diet + 120g fruits/vegetables containing Phe from 76-100mg/100g; Other: Phase D - Extra 1 Phe exchange from milk or yoghurt; Usual low Phe diet but 1 x 50 mg extra Phe exchange from milk or yoghurt; Other: Phase E - Extra 2 Phe exchanges from milk or yoghurt; Usual low Phe diet but 2 x 50 mg extra Phe exchange from milk or yoghurt eaten daily
Active Comparator: Group starting intervention with animal protein; Phase A followed by Phases D, E, B, C.	Other: Phase B - Extra 1 Phe exchange from fruits/vegetables containing Phe from 76-100mg/100g; Usual low Phe diet + 60g fruits/vegetables containing Phe from 76-100mg/100g; Other: Phase C - Extra 2 Phe exchanges from fruits/vegetables containing Phe from 76-100mg/100g; Usual low Phe diet + 120g fruits/vegetables containing Phe from 76-100mg/100g; Other: Phase D - Extra 1 Phe exchange from milk or yoghurt; Usual low Phe diet but 1 x 50 mg extra Phe exchange from milk or yoghurt; Other: Phase E - Extra 2 Phe exchanges from milk or yoghurt; Usual low Phe diet but 2 x 50 mg extra Phe exchange from milk or yoghurt eaten daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood Phe levels three times a week of patients with PKU taking extra 1 or 2 exchanges of fruits and vegetables containing 76-100mg of Phe/100g during 4 weeks each.	8 weeks
Blood Phe levels three times a week of patients with PKU taking extra 1 or 2 exchanges of animal protein during 4 weeks each.	8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Blood Phe levels three times a week with PKU taking fruits and vegetables containing 76-100mg of Phe/100g without measurement during 6 months.	6 months

Collaborators and Investigators

• Sponsor: Alex Pinto

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2019
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: June 10, 2021
• First Submitted That Met QC Criteria: February 18, 2022
• First Posted (Actual): February 21, 2022

Study Record Updates

• Last Update Posted (Actual): February 21, 2022
• Last Update Submitted That Met QC Criteria: February 18, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Phenylalanine; Fruit and vegetables; Animal protein; Vegetable protein
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Phenylketonurias
• Other Study ID Numbers: 18/BC/DTS/NO/215

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No