An interventional study of PreKUnil® LNAA Medical Food for PKU in Brain Diseases, Brain Diseases, Metabolic and Brain Diseases, Metabolic, Inborn, sponsored by Rigshospitalet, Denmark. Recruiting at 2 sites in Denmark. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-04-06.
Sponsored by Rigshospitalet, Denmark · Not applicable, Interventional, and Treatment
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.
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.
191 studies on the registry are indexed under Phenylketonurias; 40 are open to participants now.
This study's planned enrollment of 30 is above the median of 27 across 122 interventional studies indexed under Phenylketonurias.
Browse Phenylketonurias studies →Rigshospitalet, Denmark is the lead sponsor of 1,007 studies on the registry; 175 are open to participants now.
Compared within Phenylketonurias, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Brain Diseases. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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
Inclusion Criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Phase 1: LNAA Treatment Period (8 weeks) Each participant will be prescribed a specific dosage of LNAA tablets to be taken three times daily. Phase 2: Washout (2 weeks) Participants will follow a liberalized diet and refrain from taking any LNAA or amino acid supplement. Phase 3: Low-Phe diet (8 weeks) Each participant will follow a low-phenylalanine diet. LNAA therapy will not be administered during this phase.
Other: PreKUnil® LNAA Medical Food for PKU
Phase 1: Low-Phe diet (8 weeks) Each participant will follow a low-phenylalanine diet. LNAA therapy will not be administered during this phase. Phase 2: Washout (2 weeks) Participants will follow a liberalized diet and refrain from taking any LNAA or amino acid supplement. Phase 3: LNAA Treatment Period (8 weeks) Each participant will be prescribed a specific dosage of LNAA tablets to be taken three times daily.
Other: PreKUnil® LNAA Medical Food for PKU
PreKUnil® LNAA Medical Food for PKU is a commercially available active LNAA treatment product for PKU.
Dynamic positron emission tomography (PET) imaging with the fluorine-18-labeled tracer [18F]-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4'-methyl phenyl)nortropane ([18F]FE-PE2I)
Change in specific binding ratio of dopamine transporter (DaT) with \[18F\]FE-PE2I
Time frame: Crossover study: at 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Urine peripheral biomarkers of neurotransmitters
6-sulfatoxymelatonin and dopamine
Time frame: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Incidence and severity of treatment-emergent adverse events (TEAEs)
Subjects with at least one TEAE or serious TEAE
Time frame: Baseline to week 80
Adult attention deficit hyperactivity disorder (ADHD) Self-Report Scale (ASRS v1.1)
Patient-Reported Outcome Measure of attention in adults, 0-23, lowest is best
Time frame: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Symptom Checklist-90-Revised (SCL-90-R)
Patient-Reported Outcome Measure of psychopathological symptoms, percentile, lowest is best
Time frame: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Neuropsychological testing of flexibility and verbal fluency
Change in flexibility and verbal fluency using the Delis-Kaplan Executive Function System (D-KEFS) customized for study
Time frame: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Behaviour Rating Inventory of Executive Function - Adult version (BRIEF-A)
Patient-Reported Outcome Measure of executive functioning (ages 18 to 90), percentile, lowest is best
Time frame: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
PKU-QOL Questionnaire Adult version
Patient-Reported Outcome Measure of the impact of PKU and the PKU diet on quality of life
Time frame: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Computerized neuropsychological testing (responses over study iPad)
Cambridge Neuropsychological Test Automated Assessment Battery (CANTAB) customized for study
Time frame: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Brain Magnetic Resonance Imaging (MRI)
Percent of patients with anatomic anomalies on MRI of the brain
Time frame: Inclusion
Wechsler Adult Intelligence Scale (WAIS) - IV
Baseline measure of cognitive ability, 40-160, highest is best
Time frame: Inclusion
Fasting plasma amino acids, dried blood spots (finger-prick method)
Biomarkers such as the plasma Phe, Phe/Tyr ratio, Tyr/LNAA, Trp/LNAA ratio
Time frame: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Adherence to dietary treatment
3-day diet record
Time frame: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Brain perfusion measures
Dynamic PET Imaging differences between groups and with intervention
Time frame: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
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