The Impact of Frequency of Home Phenylalanine Measurements on Metabolic Control in a Population of Patients With Classic Phenylketonuria

Michał Kania36 enrolled

Overview

Recommendations regarding the frequency of phenylalanine level monitoring lack solid support from evidence derived from prospective randomized trials, including in the adult population with classic PKU. Current recommendations indicate that in adults (excluding the period of pregnancy planning and pregnancy itself), Phe levels should be assessed at least once a month or more frequently if additional indications exist. As part of this study, we plan to obtain, for the first time, high-quality data on the impact of Phe monitoring frequency on Phe control in adults. The primary objective of the study will be to assess the effect of the frequency (once a week versus once a month) of Phe level measurements on the metabolic control of phenylketonuria, as expressed by Phe concentration in DBS, in adult patients with the classic form of phenylketonuria.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Phenylketonuria (PKU)

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Informed consent to participate in the study 2. Male or female participants aged ≥18 and ≤65 years 3. Clinical diagnosis of classic phenylketonuria (PKU) documented in the medical history by at least 2 measurements of blood phenylalanine concentration ≥600 μmol/l and a predicted PAH enzyme activity \<1% (GPV), requiring treatment with a low-protein diet supplemented with special low-phenylalanine amino acid mixtures 4. Blood phenylalanine concentration in the range of 360-900 μmol/l during current therapy at the time of screening, and blood phenylalanine concentration in the range of 360-900 μmol/L during current treatment, based on the arithmetic mean of the last 3 Phe measurements from the participant's medical history (including the value from the screening) 5. Ability and willingness, in the investigator's opinion, to comply with all requirements of the study. Exclusion Criteria: * 1\. Patients who have not followed a phenylalanine (Phe)-restricted diet for 6 months prior to the start of the study or who are not willing to continue this diet 2. Phe concentration \> 900 μmol/L in any measurement taken within 6 months prior to the start of the study 3. Drug or alcohol abuse 4. A person who, in the investigator's opinion, is unable or unwilling to comply with the study requirements. Persons who are legally incapacitated will not be eligible to participate in the study 5. Current participation in another clinical trial or use of any experimental drug within 30 days prior to screening 6. Planning a pregnancy or being pregnant 7. Confirmed diagnosis of primary BH4 deficiency, documented by the presence of pathogenic mutations in both alleles of the following genes: 6-pyroyl-tetrahydrobiopterin synthase, recessive guanosine triphosphate (GTP) cyclohydrolase, sepiapterin reductase, dihydropteridine quinonoid reductase, or pterin 4 alpha-carbinolamine dehydratase 8. Use of sapropterin, sepiapterin, or pegvaliaza concurrently or within 365 days prior to screening

Outcomes

Primary Outcomes

Change in Phe concentration in the DBS measurement

Change in Phe concentration in the DBS measurement from the baseline (O1) to the 5th and 6th months in each intervention period (average of measurements O140 and O168 \[measurements once a month\] OR O119 O168 \[measurements taken once a week\]).

Time frame: from the baseline (O1) to the 5th and 6th months in each intervention period (average of measurements O140 and O168 [measurements once a month] OR O119 O168 [measurements taken once a week]).