Phenylalanine for Phenylketonuria Carriers

Overseen By Shawn Christ

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Missouri-Columbia

Must not be taking: Oral contraceptives

Disqualifiers: Obesity, Nicotine use, Neurologic conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 2 visits

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how carriers of the PKU gene, linked to a rare metabolic disorder, process the amino acid phenylalanine (Phe) and its effects on the brain and cognition. The researchers aim to determine if these carriers have higher Phe levels in the brain and whether this leads to unusual brain activity or cognitive issues after consuming foods with Phe. Participants will receive either phenylalanine or a placebo and will undergo brain scans and cognitive tests. Suitable candidates include those with a family member who has PKU and know they are carriers, or those who have been tested and confirmed as carriers. As an unphased trial, this study offers participants a unique opportunity to contribute to understanding the effects of the PKU gene without the constraints of traditional clinical trial phases.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take oral contraceptives on the day of the testing session.

What prior data suggests that phenylalanine is safe for PKU carriers?

Research shows that phenylalanine (Phe) is generally safe when consumed in normal amounts found in food. However, individuals with phenylketonuria (PKU), a condition where the body cannot process Phe properly, must avoid high levels. For those without PKU, Phe is an important nutrient found in many protein-rich foods like meat and dairy.

Studies have shown that maintaining blood Phe levels between 120 and 360 micromoles per liter is safe for people with PKU. Thus, consuming Phe in typical amounts should not pose a safety concern for those without the condition. In this study, participants will consume Phe in controlled amounts, similar to what is found in a regular diet.

Overall, no significant side effects are expected from consuming Phe at these controlled levels, especially for those without PKU. This makes participation in the trial relatively low-risk in terms of safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for managing phenylketonuria carriers, which often involves dietary restrictions and supplements, the use of phenylalanine (Phe) represents a unique approach. Researchers are excited because this treatment directly involves the amino acid that individuals with PKU have difficulty processing. This could potentially provide a more targeted way to address the biochemical imbalance at the root of the condition, leading to better management of symptoms and improved quality of life.

What evidence suggests that this trial's treatments could be effective for PKU carriers?

This trial will compare the effects of phenylalanine on individuals who carry the PKU gene with those who do not. Research has shown that some PKU gene carriers, whose bodies process phenylalanine differently, might experience changes in brain function and thinking skills when phenylalanine levels rise. Early studies found that these carriers may have lower activity of the enzyme PAH, leading to higher phenylalanine levels in the blood. This increase can potentially affect brain function and thinking abilities. One study found a connection between high phenylalanine levels, lower IQ, and difficulties with planning and decision-making tasks. While the full effects are still under investigation, evidence suggests that PKU carriers might face thinking challenges related to phenylalanine processing. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults who carry a single copy of the gene for phenylketonuria (PKU), which can affect how their body processes an amino acid called phenylalanine. Participants should be generally healthy and willing to undergo MRIs and cognitive tests.

Inclusion Criteria

I do not have PKU nor does anyone in my family.

I am between 18 and 60 years old.

I am a confirmed carrier of PKU, either through my child or genetic testing.

Exclusion Criteria

Positive cotinine urine test showing nicotine use

Contraindications for safe MRI participation such as (a) pregnancy or plans to become pregnant during the period of study enrollment; or (b) metallic objects inside the body (e.g., surgical staples left in the body following surgery, middle ear prosthesis, metal foreign objects lodged inside the eye, heart pacemakers)

Obesity as defined by a body mass index (BMI) over 30

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including PROMIS measures and cognitive tests

1 day

1 visit (in-person)

Treatment

Participants consume Phe or placebo and complete MRIs and cognitive tests at multiple timepoints

2 visits

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Phenylalanine (Phe)
• Placebo

Trial Overview The study investigates how dietary intake of phenylalanine affects brain function and cognition in PKU carriers compared to non-carriers. It involves consuming either Phe or a placebo during two separate visits, followed by MRI scans and cognitive assessments.

How Is the Trial Designed?

Group I: PKU Carriers Experimental Treatment 2 Interventions

Heterzygous carriers of a pathogenic variant of the PAH gene associated with phenylketonuria (PKU)

Group II: Non-Carriers Experimental Treatment 2 Interventions

Individuals who do not carry a pathogenic variant of the PAH gene

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07220265

Impact of Phenylalanine Elevations on Brain and Cognition ... The goal of this clinical trial is to advance our understanding of the cognitive and neurophysiologic sequelae associated with suboptimal ...

2. karger.com karger.com/lfg/article/17/1/102/910844/Are-Carriers-Unaffected-A-Literature-Review-of

Are Carriers Unaffected? A Literature Review of Metabolic ... Preliminary research has suggested that some PKU carriers exhibit reduced PAH enzyme function, and relatedly, elevated circulating Phe levels ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1098360025000528

Pegvaliase therapy for phenylketonuria: Real-world safety ... Within 24 months, 61% and 51% of participants achieved blood Phe concentrations ≤360 and ≤120 μmol/L, respectively. Reduction in blood Phe was further ...

4. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2025.1488809/full

Rethinking phenylalanine levels in phenylketonuria for ... This study evaluated the relationship between blood Phe levels, intelligence quotient (IQ), and executive functions using the Wechsler Intelligence Scale for ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8591558/

Phenylketonuria - PMC - PubMed Central - NIH Phenylketonuria (PKU; also known as phenylalanine hydroxylase (PAH) deficiency) is an autosomal recessive disorder of phenylalanine metabolism.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK1504/

Phenylalanine Hydroxylase Deficiency - GeneReviews - NCBI "Phenylketonuria (PKU)" refers specifically to severe PAH deficiency associated, in an untreated state, with plasma Phe concentrations >1,000 ...

7. mayoclinic.org mayoclinic.org/diseases-conditions/phenylketonuria/diagnosis-treatment/drc-20376308

Phenylketonuria (PKU) - Diagnosis and treatment The phenylalanine-free formula provides essential protein (amino acids) and other nutrients in a form that's safe for people with PKU . Your ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/219666Orig1s000IntegratedR.pdf

219666Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov The secondary safety data were provided by PKU-002 and PKU-004. The review team did not pool the safety data from PKU-002, PKU-. 003, and PKU ...