Effect of Large Neutral Amino Acids in Adults With Classical Phenylketonuria

NCT ID: NCT06337864

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2026-09-30

Brief 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. 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.

Conditions

Brain Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Amino Acid Metabolism, Inborn Errors; Metabolic Disease; Phenylketonurias

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LNAA supplementation, Then Low-Phe diet

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.

Group Type: EXPERIMENTAL

PreKUnil® LNAA Medical Food for PKU

Intervention Type: OTHER

PreKUnil® LNAA Medical Food for PKU is a commercially available active LNAA treatment product for PKU.

Low-Phe diet, Then LNAA supplementation

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.

Group Type: EXPERIMENTAL

PreKUnil® LNAA Medical Food for PKU

Intervention Type: OTHER

PreKUnil® LNAA Medical Food for PKU is a commercially available active LNAA treatment product for PKU.

Interventions

PreKUnil® LNAA Medical Food for PKU

PreKUnil® LNAA Medical Food for PKU is a commercially available active LNAA treatment product for PKU.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Prekulab Ltd ApS

UNKNOWN

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Allan Meldgaard Lund

Professor, MD, DMSc

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Allan Lund, Professor, MD, DMSc

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Locations

Center for Inherited Metabolic Diseases

Copenhagen, , Denmark

Site Status: RECRUITING

Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Site Status: NOT_YET_RECRUITING

Countries

Denmark

Central Contacts

Allan Lund, Professor, MD, DMSc

Role: CONTACT

allan.lund@regionh.dk

+4535451303

Olivia Fjellbirkeland, MD

Role: CONTACT

olivia.welle.fjellbirkeland@regionh.dk

Facility Contacts

Olivia Fjellbirkeland

Role: primary

Fjell.olivia@outlook.com

40552002

Olivia Welle Fjellbirkeland, MD

Role: primary

olivia.welle.fjellbirkeland@regionh.dk

Other Identifiers

H-24041030

Identifier Type: -

Identifier Source: org_study_id