Effect of Large Neutral Amino Acids in Adults With Classical Phenylketonuria

NCT06337864 | Recruiting

• 1 other identifier: H-24041030
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

  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

  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)

  Baseline to week 80

• Adult attention deficit hyperactivity disorder (ADHD) Self-Report Scale (ASRS v1.1)

  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)

  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

  Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline

Other Outcomes (5)

• Brain Magnetic Resonance Imaging (MRI)

  Inclusion

• Wechsler Adult Intelligence Scale (WAIS) - IV

  Inclusion

• Fasting plasma amino acids, dried blood spots (finger-prick method)

  Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline

Study Arms (2)

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.

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.

Other: PreKUnil® LNAA Medical Food for PKU

Interventions

PreKUnil® LNAA Medical Food for PKU OTHER

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

LNAA supplementation, Then Low-Phe diet; Low-Phe diet, Then LNAA supplementation

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Prekulab Ltd ApS: collaborator

Study Sites (2)

Center for Inherited Metabolic Diseases

Copenhagen, 2300, Denmark

RECRUITING

Copenhagen University Hospital, Rigshospitalet

Copenhagen, Denmark

NOT YET RECRUITING

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Nutritional and Metabolic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Allan Lund, Professor, MD, DMSc

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Allan Lund, Professor, MD, DMSc

CONTACT

+4535451303; allan.lund@regionh.dk

Olivia Fjellbirkeland, MD

CONTACT

olivia.welle.fjellbirkeland@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, DMSc

Model Details: 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.

Study Record Dates

• First Submitted: March 15, 2024
• First Posted: March 29, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)