Additional Dietary Large Neutral Amino Acids (LNAA) for Improved Symptoms in Adult Classical Phenylktonuria (PKU)

NCT05174559 | Unknown DMC

• 1 other identifier: LNAA for PKU
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This research investigates the effects of combining a phenylalanine restricted diet (usual care) with LNAA supplementation (adjuvant LNAA) in well-controlled adults with classical PKU. The hypothesis is that symptoms are improved in well-controlled patients who receive adjuvant LNAA therapy compared with diet monotherapy. Six symptomatic classical PKU adults will be enrolled to test the hypothesis in a small series of N-of-1 randomized controlled trials over 18-weeks. All assessments will be collected in patient's homes. A 3-month follow-up period will assess the longer-term effects of adjuvant LNAA in patients who show clinical benefit at the end of the intervention period.

Conditions

Phenylketonurias

Keywords

N-of-1 randomized controlled trials

Outcome Measures

Primary Outcomes (1)

• Personalized Symptom Index

  Assesses the subjective effect of the interventions on the personally relevant two most bothersome symptoms for the individual patient as identified in a Symptom Elicitation Interview

  3 weeks

Secondary Outcomes (8)

• Absolute plasma phenylalanine concentration, dried blood spots (finger-prick method)

  3 weeks

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

  3 weeks

• Urine peripheral biomarkers of neurotransmitters, dried urine spots

  3 weeks

• Computerized neuropsychological testing (responses over study iPad from home)

  3 weeks

• PKU-QOL Questionnaire Adult version (responses over study iPad from home)

  3 weeks

Study Arms (2)

Active LNAA

ACTIVE COMPARATOR

Active LNAA tablets are given to each participant in 3 multiple crossovers for a total exposure to the Active Comparator 3 times. The allocation is randomized within each cycle of two treatments (active/inactive). There are 3 total cycles for each participant. The intervention is PreKUnil® tablets.

Other: PreKUnil® LNAA Medical Food for PKU

Inactive LNAA

PLACEBO COMPARATOR

Inactive LNAA tablets (placebos) are given to each participant in 3 multiple crossovers for a total exposure to the Inactive Comparator 3 times. The allocation is randomized within each cycle of two treatments (inactive/active). There are 3 total cycles for each participant. The placebo intervention is PreKUnil® placebo tablets.

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. PreKUnil® inactive LNAA is a customized placebo for this research.

Active LNAA; Inactive LNAA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age ≥ 18 years
• diagnosis of classical PKU (blood phenylalanine ≥1200 µmol pre-treatment or off-treatment
• ≥ 2 PKU-related symptoms with clinically meaningful negative impact on daily life
• is in regular clinical monitoring and is treated with a PKU diet with a natural protein restriction and medical foods
• average blood phenylalanine levels between 360 and 900 µmol in past one year
• able and willing to provide consent
• demonstrates capacity to complete all requirements of the protocol
• if on medications approved by the Principal Investigator agrees not to alter dose for duration of study
• has stable daily access to phone, internet, and physical address

You may not qualify if:

• women who are breastfeeding, pregnant or planning to become pregnant in the next year
• use of adjuvant PKU treatments (LNAAs, Kuvan®, Palinziq®) within past 3 months
• use of psychotropic medications, melatonin, or any serotonin-reuptake inhibitors within past 3 months
• demonstrates insufficient motivation or time required to complete full trial

Sponsors & Collaborators

• University of Southern California: lead
• National PKU Alliance: collaborator

Study Sites (1)

University of Southern California

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Shoji Yano, MD, PhD

  Keck School of Medicine at USC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Genetics Division, Department of Pediatrics, Associate Professor of Clinical Pediatrics and Medicine, Keck School of Medicine

Model Details: Randomized controlled trials in individual patients (interventional N-of-1 RCTs) offer an alternative research design to parallel group randomized controlled trials. The N-of-1 study attempts to determine the more effective treatment for one patient using multiple crossovers, with repetition providing statistical power.

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: December 30, 2021
• Study Start: September 1, 2023
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: December 4, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)