Effects of Kuvan on Melatonin Secretion

This study is enrolling participants by invitation only.
BioMarin Pharmaceutical
Information provided by (Responsible Party):
Shoji Yano, University of Southern California
ClinicalTrials.gov Identifier:
First received: June 8, 2012
Last updated: January 17, 2013
Last verified: January 2013

This study examines the effect of tetrahydrobiopterin (Kuvan) and Large Neutral Amino Acid (LNAA) therapy on melatonin and dopamine levels in individuals with Phenylketonuria (PKU). The investigators hypothesize that Kuvan therapy will improve melatonin secretion and urine dopamine levels to some extent. However significantly greater responses in melatonin and dopamine secretions may be observed with combined treatment with Kuvan and supplementation of LNAA.

Condition Intervention Phase
Phenylketonuria (PKU)
Drug: Kuvan
Dietary Supplement: Large Neutral Amino Acid Therapy
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study to Evaluate Melatonin Secretion as a Marker of Decreased Serotonin in Individuals With PKU: Evaluation of the CNS Effects of Tetrahydrobiopterin

Resource links provided by NLM:

Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • First morning urine melatonin and dopamine [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Evaluated for each subject under 4 conditions (washout, LNAA only, Kuvan only and LNAA+Kuvan)

  • Serum Melatonin [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Evaluated for each subject under 4 conditions (LNAA, washout, Kuvan, LNAA + Kuvan)

Estimated Enrollment: 12
Study Start Date: May 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LNAA, washout, Kuvan, and LNAA+Kuvan
One group of 12 subjects, each under 4 conditions (each phase is 4 weeks)
Drug: Kuvan
Dosed at 20 mg/kg; PO; Phase 3, Phase 4
Other Name: Tetrahydrobiopterin
Dietary Supplement: Large Neutral Amino Acid Therapy
Dosed by weight: weight x .5 = total tablets per day; PO; Phase 1, Phase 4; taken with food

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Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult English-speaking patients who have confirmed PKU, and have tolerated Kuvan therapy at 20 mg/kg/day in the past, and are currently on the LNAA supplements will be considered as candidates for the study.
  • Subjects must be able to stop LNAA therapy for 4 weeks.
  • This will be determined by the subjects themselves, based on their past personal experiences.

Exclusion Criteria:

  • Individuals who have never taken Kuvan, who have never been on LNAA therapy, who are under the age of 18, or who do not speak English will be excluded.
  • Subjects who cannot stop LNAA therapy for 4 weeks will be excluded.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01617070

United States, California
Keck School of Medicine, Clinical Trials Unit at Keck Medical Center of USC
Los Angeles, California, United States, 90033
Sponsors and Collaborators
University of Southern California
BioMarin Pharmaceutical
Principal Investigator: Shoji Yano, M.D., Ph.D. USC Keck School of Medicine, Dept. of Pediatrics, Genetics Division
  More Information

Responsible Party: Shoji Yano, M.D., Ph.D, University of Southern California
ClinicalTrials.gov Identifier: NCT01617070     History of Changes
Other Study ID Numbers: USC Kuvan Melatonin
Study First Received: June 8, 2012
Last Updated: January 17, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Southern California:
Phenylketonuria (PKU)
Large Neutral Amino Acids

Additional relevant MeSH terms:
Amino Acid Metabolism, Inborn Errors
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases

ClinicalTrials.gov processed this record on March 26, 2015