PKU Skin Stripping
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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 Design
Arms and Interventions
| Arm | 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.
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| 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.
|
Outcome Measures
Primary Outcome Measures
- Control Metabolomic Profile (skin) [5 years]
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.
- PKU Metabolomic Profile (skin) [5 years]
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.
- Metabolomic Profile Change [5 years]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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A clinical diagnosis of PKU that is confirmed by elevated serum phenylalanine.
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Any age.
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Subject or the subject's legal authorized representative has given written informed consent to participate in the study.
Exclusion Criteria:
- Not applicable.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
Sponsors and Collaborators
- Children's Hospital Medical Center, Cincinnati
- BioMarin Pharmaceutical
Investigators
- Principal Investigator: Carlos E Prada, MD, Children's Hospital Medical Center, Cincinnati
Study Documents (Full-Text)
None provided.More Information
Publications
- 2015-3664