Evaluation of Behavior, Executive Function, Neurotransmitter Function and Genomic Expression Kuvan Nonresponders

NCT01274026 | Completed

• 1 other identifier: 183590-1
• Study Type: observational
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This observational study seeks to establish evidence:

1. 1.that physiologic changes, unrelated to effect on the Phenylalanine Hydroxylase (PAH) enzyme, occur in Phenylketonuria (PKU) patients who are treated with sapropterin (Kuvan®) therapy,
2. 2.that these changes may be caused by enhanced neurotransmitter synthesis in the brain or an upregulation of gene expression (increasing the ability of genes to produce functional enzymes),
3. 3.and that beneficial changes in behavior and cognition, especially executive functioning skills may result.

Conditions

Phenylketonuria; Behavior and Behavior Mechanisms; PAH Gene Expression

Keywords

phenylketonuria; PKU; phenylalanine; neurotransmitters; gene; Kuvan; sapropterin

Outcome Measures

Primary Outcomes (2)

• change in behavior as a result of Kuvan administration

  This study seeks to establish evidence that behavioral changes, unrelated to blood phenylalanine levels, occur in PKU patients who are treated with Kuvan therapy, and that beneficial changes in behavior as measured by validated measurement questionnaires may result.

  assessment during a 4 week trial of Kuvan

• change in executive function as a result of Kuvan administration

  This study seeks to establish evidence: that cognitive changes unrelated to blood phenylalanine levels occur in PKU patients who are treated with Kuvan therapy, and that beneficial changes in cognition, especially executive functioning skills as measured by validated measurement questionnaires may result.

  assessment during a 4 week trial of Kuvan

Secondary Outcomes (1)

• change in neurotransmitter synthesis

  assessment during a 4 week trial of Kuvan administration

Study Arms (1)

evaluation of benefit of sapropterin

Intervention 'sapropterin dihydrochloride': 20 individuals, either known to be non-responsive, or naive to sapropterin, are given a 4 week administration of sapropterin. Pre-, and Post- evaluation of behavior, executive function, neurotransmitter function, and genomic expression are assessed and evaluated for change.

Drug: sapropterin dihydrochloride

Interventions

sapropterin dihydrochloride DRUG

In 30 PKU patients found previously to exhibit no decrease in blood PHE levels behavioral and cognitive function, neurotransmitter levels, and gene expression of enzyme activity will be measured at baseline and after 4 weeks of Kuvan administration. Rating inventories of executive function performance and behavior will be administered to patients and parents. Urine neurotransmitters, blood microarray expression, and plasma amino acids will be measured (plasma PHE and TYR levels will also be measured at weeks 1 and 2). Nutrient analysis of 3 day food diaries will be conducted.

Also known as: Kuvan

evaluation of benefit of sapropterin

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Study participants were solicited from treated patients diagnosed with PKU who are followed by our clinic. Participants were initially limited to those who had undergone a trial with sapropterin (FDA approved drug available for treatment) as part of their clinical care and been found to be non-responsive. Subsequently, with IRB approval, some patients diagnosed with PKU from our clinic population who were naive to sapropterin were added to the study.

You may qualify if:

• established Hayward Genetics Center patients:
• confirmed diagnosis of PKU,
• aged 2-21 years,

You may not qualify if:

• pregnancy
• preexisting cognitive disorder or concurrent disease that would interfere with participation,
• documented equal to or greater than 20% decrease in blood PHE levels as a response to sapropterin administration,
• receiving neurotransmitter supplementation or medication for attention deficit hyperactivity disorder (ADHD),
• received sapropterin therapy in the 2 months prior to the study

Sponsors & Collaborators

• Tulane University School of Medicine: lead
• BioMarin Pharmaceutical: collaborator

Study Sites (1)

Tulane University Health Science Center

New Orleans, Louisiana, 70112, United States

Location

MeSH Terms

Conditions

Phenylketonurias; Behavior

Interventions

sapropterin

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

• Hans C Andersson, MD

  Tulane University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2011
• First Posted: January 11, 2011
• Study Start: January 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)