PKU Skin Stripping

A Novel Approach Integrating Non-invasive Skin Tape-stripping to Evaluate and Monitor Patients With Phenylketonuria (PKU)

PURPOSE OF STUDY: To determine if a non-invasive skin stripping technique can be used to detect individuals with phenylalanine abnormalities, and to monitor dietary and/or drug effects over time.

Study Overview

• Status: Completed
• Conditions: Phenylketonurias
• Intervention / Treatment: Other: Skin Tape; Diagnostic test: Blood Draw

Detailed Description

This study will determine if a non-invasive skin stripping technique can be used to detect individuals with phenylalanine abnormalities, and to monitor dietary and/or drug effects over time. To do this 50 children and adults with phenylalanine abnormalities and up to 50 unaffected controls will be recruited to this study. The 50 affected individuals will have their metabolomic profile analyzed from up to 3 skin-stripping samples over time and compared to their serum amino acid profile in both dried blood spots and a typical blood sample. The unaffected controls will provide one skin-stripping sample. Clinical data regarding compliance with dietary therapy and other medications will be collected to determine other effects on the metabolome.

• Study Type: Observational
• Enrollment (Actual): 86

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Phenylketonuria (PKU) is a serious metabolic disorder characterized by intolerance to the dietary intake of phenylalanine. When untreated, older children can show the following clinical manifestations: microcephaly, epilepsy, a musty body odor, decreased skin and hair pigmentation, eczema, severe intellectual disability, and behavioral problems.

Description

Inclusion Criteria:

1. A clinical diagnosis of PKU that is confirmed by elevated serum phenylalanine.
2. Any age.
3. Subject or the subject's legal authorized representative has given written informed consent to participate in the study.

Exclusion Criteria:

• Not applicable.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants with PKU; Patients with classical PKU phenotype (serum phenylalanine concentration > 10 mg/dL on a normal diet at diagnosis) # ~25; Patients with hyperphenylalaninemia (serum phenylalanine concentration < 10 mg/dL on a normal diet at diagnosis) # ~15; Patients with PKU on therapy with Kuvan # ~10	Other: Skin Tape; Skin sample collection: samples of human stratum corneum will be obtained with squame adhesive tape disks typically at the time of their clinic appointment. The tape will be placed on the inside of the forearm and the procedure will be repeated up to five times per patient to have sufficient corneocytes for analysis. This type of sampling is non-invasive.; Diagnostic test: Blood Draw; Blood specimens: blood will be obtained for serum amino acids/phenylalanine levels. This sample is obtained for disease monitoring as part of routine standard of care. Results from up to three clinic visits will be correlated with the tape sample obtained on the same day.
Non-PKU Control; Study Controls: Up to 50 children and adults without a known metabolic disorder.	Other: Skin Tape; Skin sample collection: samples of human stratum corneum will be obtained with squame adhesive tape disks typically at the time of their clinic appointment. The tape will be placed on the inside of the forearm and the procedure will be repeated up to five times per patient to have sufficient corneocytes for analysis. This type of sampling is non-invasive.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Control Metabolomic Profile (skin)	The establishment of normative data for the skin metabolome will provide a baseline for assessing changes in the skin metabolome that occur during development and with disease. By exhaustive extraction of the adhesive tapes with organic solvents, the investigators will analyze the metabolome of the stratum corneum with developed targeted methods for amino acids. The analysis will be performed using ultra high performance liquid chromatography - quadrupole time of flight mass spectrometry (UPLCQTOF-MS) to identify biochemical changes in the tape-stripped skin metabolome. With the comparative intensity/concentration results of identified metabolites, a subsequent metabolic network reconstruction will be carried out to reveal the underlying mechanism perturbed in PKU and metabolic response to diet or therapeutic interventions.	5 years
PKU Metabolomic Profile (skin)	By exhaustive extraction of the adhesive tapes with organic solvents, the investigators will analyze the metabolome of the stratum corneum with developed targeted methods for amino acids. The analysis will be performed using ultra high performance liquid chromatography - quadrupole time of flight mass spectrometry (UPLCQTOF-MS) to identify biochemical changes in the tape-stripped skin metabolome. With the comparative intensity/concentration results of identified metabolites, a subsequent metabolic network reconstruction will be carried out to reveal the underlying mechanism perturbed in PKU and metabolic response to diet or therapeutic interventions.	5 years
Metabolomic Profile Change	Determine if the metabolomic profile changes over time in patients with PKU. By exhaustive extraction of the adhesive tapes with organic solvents, the investigators will analyze the metabolome of the stratum corneum with developed targeted methods for amino acids. The analysis will be performed using ultra high performance liquid chromatography - quadrupole time of flight mass spectrometry (UPLCQTOF-MS) to identify biochemical changes in the tape-stripped skin metabolome. With the comparative intensity/concentration results of identified metabolites, a subsequent metabolic network reconstruction will be carried out to reveal the underlying mechanism perturbed in PKU and metabolic response to diet or therapeutic interventions.	5 years

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: BioMarin Pharmaceutical
• Investigators: Principal Investigator: Carlos E Prada, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

General Publications

• Holleran WM, Ziegler SG, Goker-Alpan O, Eblan MJ, Elias PM, Schiffmann R, Sidransky E. Skin abnormalities as an early predictor of neurologic outcome in Gaucher disease. Clin Genet. 2006 Apr;69(4):355-7. doi: 10.1111/j.1399-0004.2006.00589.x. No abstract available.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 12, 2015
• Primary Completion (ACTUAL): December 1, 2020
• Study Completion (ACTUAL): April 1, 2021

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (ACTUAL): April 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 28, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Phenylketonurias
• Other Study ID Numbers: 2015-3664

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No