PKU Skin Stripping

NCT04368624 | Completed

• 1 other identifier: 2015-3664
• Study Type: observational
• Target: 86
• Locations: 1 country
• Sites: 1

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.

Conditions

Phenylketonurias

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

Participants with PKU

1. Patients with classical PKU phenotype (serum phenylalanine concentration \> 10 mg/dL on a normal diet at diagnosis) # \~25 2. Patients with hyperphenylalaninemia (serum phenylalanine concentration \< 10 mg/dL on a normal diet at diagnosis) # \~15 3. Patients with PKU on therapy with Kuvan # \~10

Other: Skin Tape; Diagnostic Test: Blood Draw

Non-PKU Control

Study Controls: Up to 50 children and adults without a known metabolic disorder.

Other: Skin Tape

Interventions

Skin Tape OTHER

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.

Non-PKU Control; Participants with PKU

Blood Draw DIAGNOSTIC_TEST

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.

Participants with PKU

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• Not applicable.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• BioMarin Pharmaceutical: collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (1)

• 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.

  PMID: 16630170 BACKGROUND

Biospecimen

Retention: NONE RETAINED

Skin

MeSH Terms

Conditions

Phenylketonurias

Interventions

Surgical Tape; Blood Specimen Collection

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

Intervention Hierarchy (Ancestors)

Surgical Fixation Devices; Surgical Equipment; Equipment and Supplies; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Carlos E Prada, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: April 30, 2020
• Study Start: October 12, 2015
• Primary Completion: December 1, 2020
• Study Completion: April 1, 2021
• Last Updated: July 28, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)