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A Pilot Study on Diurnal Variation

This study has been terminated.
(Participants found the study procedures to be too cumbersome and no longer wanted to participate)
BioMarin Pharmaceutical
Information provided by (Responsible Party):
Dr. Linda Randolph, Children's Hospital Los Angeles Identifier:
First received: March 4, 2013
Last updated: March 21, 2016
Last verified: March 2016
This self-controlled, prospective, pilot study is designed to gather information regarding the diurnal variation (changes that occur each day) in the levels of plasma phenylalanine (Phe) and tyrosine in patients with phenylketonuria (PKU) and in the non-PKU population.

Condition Intervention
Phenylketonuria (PKU)
Drug: Kuvan

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Pilot Study on the Diurnal Variation in PKU Patients With Kuvan

Resource links provided by NLM:

Further study details as provided by Children's Hospital Los Angeles:

Primary Outcome Measures:
  • Changes in Plasma Phe and Tyrosine Levels [ Time Frame: Baseline and 4 weeks ]
    To evaluate the patterns of change in plasma Phe and tyrosine levels between the Baseline visit and 4 week visit for each arm.

Enrollment: 6
Study Start Date: March 2013
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PKU Participants (Arm 1)
  • Subjects will be administered Kuvan once daily.
  • They will undergo several blood draws, including a 24-Hour Blood Assessment (at Study Visit #2 before the commencement of Kuvan), plasma Phe/Tyr draws (at Study Visits #3, 4, and 5), and another 24-Hour Blood Assessment (at Study Visit #6).
Drug: Kuvan
Only PKU participants (Arm 1) will be administered Kuvan once daily either at a dose of 20 mg/kg/day (if the PKU participant is not currently taking Kuvan) or at the subject's regular dose (if the PKU participant is currently taking Kuvan). They will remain on Kuvan for 4 weeks.
No Intervention: Control Group (Arm 2)
  • Subjects allocated into this group will be healthy, non-PKU individuals that may be a relative (ex: sibling) of a PKU participant, but they don't have to be a blood relation.
  • These subjects will undergo a 24-Hour Blood Assessment (at Study Visit #2).

Detailed Description:

Phenylketonuria (PKU) is a rare genetic metabolic disease caused by a mutation that codes for an enzyme that converts the essential amino acid phenylalanine (Phe) into tyrosine. An absence or deficiency of this enzyme activity results in a Phe elevation, where higher Phe levels result in neurological damage. Diurnal variations of Phe levels have been observed in PKU patients in a 24-hour period.

As Kuvan has shown to stabilize Phe levels in PKU patients over time, our hypothesis is that this can be demonstrated within a 24-hour period of observation and indicate therefore that Kuvan may correlate with a lower plasma Phe variability. This study on PKU patients' diurnal variation will also provide important information as to the current method of blood Phe monitoring in a clinical setting to learn more about the optimal way to measure Phe concentration.

The study will last about 4 weeks (6 study visits) for the PKU participants and about 1 week (2 study visits) for the control group.

Participants will be required to follow a recommended diet, complete a dietary log, and undergo several blood draws, including a 24-Hour Blood Assessment in which blood will be obtained 8 times throughout the day.


Ages Eligible for Study:   4 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:


  • Subject has a confirmed diagnosis of PKU with hyperphenylalaninemia documented by a fasting Phenylalanine level of at least 360 umol/L (6 mg/dL)
  • Patient is at least 4 years old (there is no upper age limit for this study)
  • Willing and able to provide written authorization or, if under the age of 18 years, provide written assent (if required) and written patient authorization by a parent or legal guardian
  • Willing to undergo study related procedures including commencing Kuvan treatment for patient not currently on treatment; temporary discontinuation of Kuvan for patient on treatment; and completing the 24-Hour Blood Assessment
  • Authorized to provide personal health information
  • Subjects should not be pregnant and willing to use appropriate birth control during the study


  • Healthy, non-PKU individuals. They will be age-sex matched to the PKU group. They may be a relative (ex: sibling) of a PKU participant, but they don't have to be a blood relation.
  • Individual is at least 4 years old (there is no upper age limit)
  • Willing and able to provide written consent or, if under the age of 18 years, provide written assent and written participant authorization by a parent or legal guardian
  • Authorized to provide personal health information

Exclusion Criteria (BOTH ARMS):

  • Subjects who do not meet all the inclusion criteria
  • Age < 4 years
  • Concomitant medical problems or medications which at the discretion of the principal investigator would put participant at health risk or prevent them from completing study.
  • If female, unwillingness to use birth control during the period of the study drug administration (this doesn't apply to Arm 2)
  Contacts and Locations
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Please refer to this study by its identifier: NCT01806051

United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Sponsors and Collaborators
Dr. Linda Randolph
BioMarin Pharmaceutical
Principal Investigator: Linda M. Randolph, MD Children's Hospital Los Angeles
  More Information

Responsible Party: Dr. Linda Randolph, Head, Division of Medical Genetics, Children's Hospital Los Angeles Identifier: NCT01806051     History of Changes
Other Study ID Numbers: CCI-12-00178
Study First Received: March 4, 2013
Results First Received: March 21, 2016
Last Updated: March 21, 2016

Additional relevant MeSH terms:
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
Metabolic Diseases processed this record on May 24, 2017