A Pilot Study on Diurnal Variation

• Sponsor: Dr. Linda Randolph (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01806051
• Collaborator: BioMarin Pharmaceutical (Industry)
• Enrollment: 6
• Location: 1
• Arms: 2
• Duration (Months): 14
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Phenylketonuria (PKU)	Drug: Kuvan	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Official Title: A Pilot Study on the Diurnal Variation in PKU Patients With Kuvan
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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).

Outcome Measures

Primary Outcome Measures

1. Changes in Plasma Phe and Tyrosine Levels [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

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

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027

Sponsors and Collaborators

• Dr. Linda Randolph
• BioMarin Pharmaceutical

Investigators

• Principal Investigator: Linda M. Randolph, MD, Children's Hospital Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Linda Randolph, Head, Division of Medical Genetics, Children's Hospital Los Angeles
• ClinicalTrials.gov Identifier: NCT01806051
• Other Study ID Numbers: CCI-12-00178
• First Posted: Mar 7, 2013
• Last Update Posted: Apr 20, 2016
• Last Verified: Mar 1, 2016

• Additional relevant MeSH terms: Phenylketonurias

Study Results

Participant Flow

Recruitment Details	No data was collected because all of the participants who consented to participate in the study withdrew due to the procedural challenges of remaining in the study (e.g. the PM blood draws were too disruptive).

Arm/Group Title	All Participants
Arm/Group Description	Participants signed the consent forms and withdrew because they found the study procedures to be too cumbersome.
Period Title: Overall Study
STARTED	6
COMPLETED	0
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description
Overall Participants	0
Age (Count of Participants)
Sex: Female, Male (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Changes in Plasma Phe and Tyrosine Levels
Description	To evaluate the patterns of change in plasma Phe and tyrosine levels between the Baseline visit and 4 week visit for each arm.
Time Frame	Baseline and 4 weeks

Outcome Measure Data

Analysis Population Description

Participants withdrew before any data were collected.

Arm/Group Title	PKU Participants (Arm 1)	Control Group (Arm 2)
Arm/Group Description	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). 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.	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).
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	Participants withdrew before any data were collected.
Arm/Group Title	PKU Participants (Arm 1)		Control Group (Arm 2)
Arm/Group Description	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). 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.		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).
All Cause Mortality
	PKU Participants (Arm 1)		Control Group (Arm 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PKU Participants (Arm 1)		Control Group (Arm 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	PKU Participants (Arm 1)		Control Group (Arm 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.