Brain DiseasesNCT06337864
Effect of Large Neutral Amino Acids in Adults With Classical Phenylketonuria
A study testing PreKUnil® LNAA Medical Food for PKU in people with Brain Diseases and Brain Diseases, Metabolic, run by Copenhagen University Hospital, Rigshospitalet at 2 sites in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Brain Diseases, Brain Diseases, Metabolic, Brain Diseases, Metabolic, Inborn
- What is being tested?
- PreKUnil® LNAA Medical Food for PKU
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesDenmark
- Study dates
- 1 Nov 2024to 30 Sep 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Olivia Fjellbirkeland, MD contact
Denmark2 sites, 2 recruiting
- Recruiting
Center for Inherited Metabolic Diseases
Copenhagen, 2300
Olivia Fjellbirkeland, 40552002, Fjell.olivia@outlook.com
- Not yet recruiting
Copenhagen University Hospital, Rigshospitalet
Copenhagen
Olivia Welle Fjellbirkeland, MD, olivia.welle.fjellbirkeland@regionh.dk
About this study
Official title: Safety and Efficacy of Treatment With Large Neutral Amino Acids in Patients With Classical Phenylketonuria
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.
Read the detailed description
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.
- Conditions
- Brain Diseases, Brain Diseases, Metabolic, Brain Diseases, Metabolic, Inborn, Genetic Diseases, Inborn, Metabolism, Inborn Errors, Amino Acid Metabolism, Inborn Errors
- Being tested
- PreKUnil® LNAA Medical Food for PKU
- Medical subject headings
- Brain Diseases, Brain Diseases, Metabolic, Brain Diseases, Metabolic, Inborn, Genetic Diseases, Inborn, Metabolism, Inborn Errors, Amino Acid Metabolism, Inborn Errors, Metabolic Diseases, Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PreKUnil® LNAA Medical Food for PKUOther
PreKUnil® LNAA Medical Food for PKU is a commercially available active LNAA treatment product for PKU.
| Study group | Role | What they receive |
|---|---|---|
| LNAA supplementation, Then Low-Phe diet | Experimental | 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. Receives: Other: PreKUnil® LNAA Medical Food for PKU |
| Low-Phe diet, Then LNAA supplementation | Experimental | 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. Receives: Other: PreKUnil® LNAA Medical Food for PKU |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Crossover study: at 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Secondary outcomes (8)
Urine peripheral biomarkers of neurotransmitters
6-sulfatoxymelatonin and dopamine
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2024
- Study start1 Nov 2024
- Primary completionSep 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain DiseasesStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, open-label, crossover trial. Participants will be randomly assigned to receive either LNAA treatment or the classic dietary treatment for 8 weeks, followed by a washout period of 2 weeks before receiving the other intervention for 8 weeks. Additionally, a healthy control group will be recruited for baseline measures.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Prekulab Ltd ApS
- Responsible party
- Principal investigator, Allan Meldgaard Lund, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Allan Lund, Professor, MD, DMSc, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06337864
- Sponsor's protocol ID
- H-24041030
- Status last verified
- Apr 2025
- First submitted
- 15 Mar 2024
- Last updated
- 6 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Treatment With Large Neutral Amino Acids in Patients With Classical Phenylketonuria
- ClinicalTrials.gov ID
- NCT06337864
- Acronym / sponsor ID
- H-24041030
- Conditions
- Brain Diseases, Brain Diseases, Metabolic, Brain Diseases, Metabolic, Inborn, Genetic Diseases, Inborn, Metabolism, Inborn Errors, Amino Acid Metabolism, Inborn Errors
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- Prekulab Ltd ApS
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 29 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized, open-label, crossover trial. Participants will be randomly assigned to receive either LNAA treatment or the classic dietary treatment for 8 weeks, followed by a washout period of 2 weeks before receiving the other intervention for 8 weeks. Additionally, a healthy control group will be recruited for baseline measures.
| Arm | Type | Receives |
|---|---|---|
| LNAA supplementation, Then Low-Phe diet | Experimental | Other: PreKUnil® LNAA Medical Food for PKUPhase 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. |
| Low-Phe diet, Then LNAA supplementation | Experimental | Other: PreKUnil® LNAA Medical Food for PKUPhase 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PreKUnil® LNAA Medical Food for PKUPreKUnil® LNAA Medical Food for PKU is a commercially available active LNAA treatment product for PKU. | Other | LNAA supplementation, Then Low-Phe diet, Low-Phe diet, Then LNAA supplementation |
Primary outcome
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)
Time frame: Crossover study: at 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Change in specific binding ratio of dopamine transporter (DaT) with [18F]FE-PE2I
8 secondary outcomes
Urine peripheral biomarkers of neurotransmitters
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)
Time frame: Baseline to week 80
Adult attention deficit hyperactivity disorder (ADHD) Self-Report Scale (ASRS v1.1)
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)
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
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)
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
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)
Time frame: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Olivia Fjellbirkeland, MD contact
Allan Lund, Professor, MD, DMSc principal investigator
Copenhagen University Hospital, Rigshospitalet
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PreKUnil® LNAA Medical Food for PKU in people with Brain Diseases and Brain Diseases, Metabolic, run by Copenhagen University Hospital, Rigshospitalet at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Allan Lund, Professor, MD, DMSc (+4535451303, allan.lund@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: Crossover study: at 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2025.