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Effects of Kuvan on Melatonin Secretion

This study has been completed.
BioMarin Pharmaceutical
Information provided by (Responsible Party):
Shoji Yano, University of Southern California Identifier:
First received: June 8, 2012
Last updated: November 8, 2016
Last verified: November 2016
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: 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:
  • Serum Melatonin at the End of 4 Weeks [ Time Frame: measured every 4 weeks up to 16 weeks ]
    Evaluated for each subject under 4 conditions (washout, LNAA only, Kuvan only and LNAA+Kuvan)

  • Urine 6-sulfatoxymelatonin at the End of 4 Weeks [ Time Frame: measured every 4 weeks up to 16 weeks ]
    Evaluated for each subject under 4 conditions (washout, LNAA only, Kuvan only and LNAA+Kuvan)

  • Urine Dopamine at the End of 4 Weeks [ Time Frame: measured every 4 weeks up to 16 weeks ]
    Evaluated for each subject under 4 conditions (washout, LNAA only, Kuvan only and LNAA+Kuvan)

Enrollment: 10
Study Start Date: May 2012
Study Completion Date: December 2014
Primary Completion Date: December 2014 (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
Other Name: LNAA

  Show Detailed Description


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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 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

Nielsen JB, Lou H, Güttler F. Effects of diet discontinuation and dietary tryptophan supplementation on neurotransmitter metabolism in phenylketonuria. Brain Dysfunction 1:51-56. 1988.

Responsible Party: Shoji Yano, M.D., Ph.D, University of Southern California Identifier: NCT01617070     History of Changes
Other Study ID Numbers: USC Kuvan Melatonin
Study First Received: June 8, 2012
Results First Received: November 8, 2016
Last Updated: November 8, 2016

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

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
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Protective Agents
Central Nervous System Depressants processed this record on May 25, 2017