The Effects of CGMP in Children and Adults With PKU

The study is a randomised controlled trial with a crossover design conducted at several international study centres.

The study population is early and continuously treated patients with PKU that are adhering to their prescribed diet.

The participants will be given both a CGMP based protein substitute and a free AA based protein substitute as their main protein source on two different 12-week periods in a crossover design. The two periods will be separated by a 4 week wash out period.

The protein substitutes will be consumed daily together with the patient's regular low protein diet during the intervention periods.

Primary Objective The primary objective of the study is to investigate the effects of a CGMP based formula compared to an AA based formula upon mean plasma Phe levels after 12 weeks of daily intake in patients with PKU.

Secondary Objectives The secondary objectives of the study are to investigate if a CGMP based formula compared to an AA based formula in PKU patients provides any long-term health benefits concerning gut health, inflammation, oxidative stress and product acceptability.

Inclusion criteria

• PKU patient diagnosed on newborn screening (NBS).
• > 50% of protein intake from protein substitutes.
• (CHILDREN) Dietary intake of ≤ 1000 mg Phe from natural protein or ≤20 g natural protein inclusive of fruit and vegetables per day.
• (ADULTS) Dietary intake of ≤ 1500 mg Phe from natural protein or ≤ 30 g natural protein inclusive of fruit and vegetables per day.
• (CHILDREN) Three out of the last four consecutive Phe measurements within the target range (≤360 µmol/L in patients aged 4-12 years).
• (ADULTS) Two out of the last four consecutive Phe measurements within the target range (≤600 µmol/L for adults).
• Male or female aged 4-12 years or 18 years and over.
• Early and continuously treated. Adherent to their prescribed PKU diet consisting of a protein-restricted diet and free AA based protein substitute.
• Otherwise in good general health as evidenced by medical history.
• Able to provide written informed consent (patient or parent/guardian).
• Able to comply with the study protocol and take study product according to the opinion of the PI.
• Protein substitute intake provided by L-amino acid supplements only.
• (ADULTS) No studies have been done in pregnant women. To ensure patients safety, female patients of childbearing potential must have a negative pregnancy test prior to completing the screening procedures.
• (ADULTS) All female patients of childbearing potential and sexually mature males should be willing to use a medically accepted method of contraception throughout the study.
• Successful 3-day PKU Sphere taste test.

Exclusion criteria

• Concomitant diseases / disorders such as but not limited to renal or gut disease / disorders and diabetes.
• Currently or previously treated with tetrahydrobiopterin (BH4), pegylated recombinant phenylalanine ammonia lyase (PEG PAL), large neutral amino acids.
• Previous intake of CGMP for more than four consecutive weeks.
• Having a current infection.
• Known soya, milk or fish allergies / intolerance.
• Patients who are currently participating in, plan to participate in, or have participated in an interventional investigational drug, food or medical device trial within 30 days prior to screening visit.
• Where applicable, patients not covered by Health Insurance System and/or not in compliance with the recommendations of National Law in force.