A Pilot Study on Diurnal Variation

NCT ID: NCT01806051

Last Updated: 2016-04-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2014-05-31

Brief Summary

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.

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.

Conditions

Phenylketonuria (PKU)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Kuvan

Intervention Type: DRUG

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.

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).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

PKU PARTICIPANTS (ARM 1):

• 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

CONTROL GROUP (ARM 2):

• 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

• 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)

• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

Dr. Linda Randolph

OTHER

Sponsor Role: lead

Responsible Party

Dr. Linda Randolph

Head, Division of Medical Genetics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Linda M. Randolph, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Los Angeles

Locations

Children's Hospital Los Angeles

Los Angeles, California, United States

Countries

United States

Other Identifiers

CCI-12-00178

Identifier Type: -

Identifier Source: org_study_id