ClinicalTrials.gov record NCT06337864

Effect of Large Neutral Amino Acids in Adults With Classical Phenylketonuria

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 6, 2026

Safety and Efficacy of Treatment With Large Neutral Amino Acids in Patients With Classical Phenylketonuria

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
Healthy volunteersAcceptedPeople who do not have the condition being studied who are allowed to take part. Some studies include both people with the condition and healthy volunteers; others may enrol only healthy volunteers.
Age18 years old to 50 years old
SexAll
LocationDenmark
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This randomized, open-label crossover trial compares large neutral amino acid (LNAA) tablets with the standard low-phenylalanine diet in adults with classical PKU. Each participant receives one treatment for eight weeks, a two-week washout, then the other treatment for eight weeks. Healthy controls provide baseline measures and an optional open-label extension studies longer-term safety and effects.

What it is studying. The study tests LNAA supplementation versus the standard low-phenylalanine diet to measure effects on brain dopamine synthesis, peripheral neurotransmitter biomarkers, cognitive performance, mental-health measures, and safety.

What the researchers hope to learn. To evaluate LNAA as a potential alternative to the conventional low-phenylalanine diet; to measure effects on cerebral dopamine synthesis and peripheral neurotransmitter biomarkers; to assess cognitive and mental-health outcomes and collect safety data; and to improve understanding of PKU pathophysiology to inform future personalized management approaches.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

The overall aim of this study is to evaluate LNAA treatment as a potential alternative to conventional dietary treatment for PKU. This study investigates the effects of LNAA treatment compared to the classic dietary treatment on cerebral dopamine synthesis in patients with classic PKU. We will assess LNAAs effectiveness on neurotransmitter synthesis, cognitive function, mental health, and safety, compared to the standard diet.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Other
  • PreKUnil® LNAA Medical Food for PKU

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • Patients ≥ 18 years of age with Classical PKU molecularly confirmed via the finding of two pathogenic variants in the phenylalanine hydroxylase (PAH) gene and/or historical evidence of Phe concentrations ≥1200 μmol/L in the medical history
  • Treatment initiation within the first month of life
  • Intelligence quotient over 84, based upon the baseline neuropsychological evaluation
  • Conventional dietary treatment up to minimum 15 years of age
  • Signed informed consent
  • Willing and able to comply with the protocol and study procedures

Exclusion criteria

  • Unable or unwilling to adhere to the requirements of the study
  • A female who is pregnant or breastfeeding or planning to get pregnant during the study period
  • Concomitant medication that may interfere with the PET analysis, as judged by the investigator
  • A serious neuropsychiatric disease that could interfere with the subject's ability to participate in the study at the discretion of the investigator
  • Concomitant treatment with BH4 supplementation (sapropterin) or Pegvaliase-pqpz (PALYNZIQ)
  • Failing to submit at least one blood Phe home sample during the year before study initiation
  • Standard MRI contraindications
  • Body weight over 110 kg

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Detailed description from the registry

Standard treatment for Phenylketonuria (PKU) involves a lifelong, phenylalanine-restricted diet. Strict adherence to the diet is crucial, but often challenging. Large neutral amino acid (LNAA) supplementation is a potential alternative therapeutic approach for PKU management. The proposed mechanism involves competitive inhibition of phenylalanine (Phe) transport across the blood-brain barrier by high-dose LNAA, leading to reduced brain Phe levels. However, further investigation is needed to validate its efficacy and safety for PKU management. A randomized, open-label, crossover trial will be conducted to assess the safety and efficacy of LNAA supplementation in PKU patients. After completion of the crossover study, participants will have the option to participate in an open-label extension study aimed at evaluating the long-term safety and efficacy of LNAA. A healthy control group will be recruited to obtain baseline outcome measures. This project is expected to provide much-needed insights into the potential of LNAA in PKU management. The study also aims to gain a deeper understanding of the underlying pathophysiology of the disease. Finally, this work could lead to more personalized management strategies for PKU patients.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

You will take part in a randomized crossover of two 8‑week periods (one with LNAA tablets taken three times daily and one following a low‑phenylalanine diet) separated by a 2‑week washout with a liberalized diet. Study visits include repeated brain PET scans using an injected tracer (and MRI where needed), urine and blood samples, computerized and paper neuropsychological tests, quality‑of‑life and symptom questionnaires, and reporting of any side effects. After the crossover you may be offered an open‑label extension to evaluate longer‑term safety and effects. Healthy controls will have baseline measurements for comparison (registry does not specify their procedures in detail).

How the study is structured. Randomized, open-label crossover study. Participants are randomly assigned to either take LNAA tablets for eight weeks then follow a low-Phe diet for eight weeks, or the reverse, with a two-week washout between periods. Assessments include brain PET imaging, urine neurotransmitter markers, neuropsychological tests, patient questionnaires, and safety monitoring. A healthy control group supplies baseline outcome measures and an optional long-term open-label extension is available after the crossover.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The listed sites are in Denmark. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on phenylketonuria

Clinical trials38 trials listed for phenylketonuriaEvery trial the registry lists for phenylketonuria, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in phenylketonuria researchLatest monthly update: September 2026. Includes: Diet supply gaps. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Nov 1, 2024
Primary completion
September 2026 (estimated)
Study completion
Sep 30, 2026 (estimated)
Target enrollment
30 participants (estimated)
Last updated on registry
Apr 6, 2025
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Rigshospitalet, Denmark
Principal investigator
Allan Meldgaard Lund, Professor, MD, DMSc
Rigshospitalet, Denmark
Collaborators
  • Prekulab Ltd ApS

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (2)

Terms used on this page · explanations by MedicalUpdates.ai

baseline
Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
Concomitant medication
Other medicines a participant takes during the study. Some must be reported; some are restricted.
PET
A scan in which a small amount of a radioactive tracer is injected so that activity in tissues can be seen. Often combined with a CT or MRI scan.
MRI
A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one.
contraindications
A reason a particular test or treatment should not be used for a person, for example a metal implant that rules out an MRI scan.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
Standard treatment
Treatment generally considered appropriate for a condition in a particular clinical setting. It can vary by patient, place and over time. In many studies the new treatment is added to, or compared with, standard of care.
randomized
Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
open-label
No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
crossover
Each participant receives more than one intervention, one after the other, usually with a gap (a washout) in between. Participants act as their own comparison.
open-label extension
A continuation study in which participants who completed an earlier study can keep receiving the treatment, usually with everyone knowing what they are given.
control group
The group the study treatment is compared with. It may receive a placebo, an existing treatment (active comparator), a sham procedure, or no intervention.
outcome measures
Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

← Back to clinical trials