Status:

COMPLETED

Nitisinone for Type 1B Oculocutaneous Albinism

Lead Sponsor:

National Eye Institute (NEI)

Collaborating Sponsors:

National Human Genome Research Institute (NHGRI)

Conditions:

Albinism

Vision Loss

Eligibility:

All Genders

18+ years

Phase:

PHASE1

PHASE2

Brief Summary

Background: \- Oculocutaneous albinism, type 1B (OCA1B) is a genetic disease caused by problems in the gene that makes tyrosine. Tyrosine is an amino acid needed to produce pigment in the skin, hair,...

Detailed Description

Objective: The primary objective of this study is to evaluate oral nitisinone as a treatment that improves ocular pigmentation in adult participants with oculocutaneous albinism, type 1B (OCA1B). Seco...

Eligibility Criteria

Inclusion

  • INCLUSION CRITERIA:
  • To be eligible, the following inclusion criteria must be met, when applicable.
  • Participant must be 18 years of age or older.
  • Participant must understand and sign the protocol s informed consent document.
  • Participant must have normal renal function, liver function, and platelet counts or have mild abnormalities no greater than grade 1 as defined by the Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
  • Any female participant of childbearing potential must have a negative pregnancy test at screening and must be willing to undergo pregnancy testing immediately prior to the start of the investigational product and while on the investigational product.
  • Any female participant of childbearing potential and any male participant able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse, or must agree to practice two effective methods of contraception while taking the investigational product and for at least two months following the last dose of investigational product. Acceptable methods of contraception include:
  • Hormonal contraception (i.e., birth control pills, injected hormones, dermal patch, or vaginal ring),
  • Intrauterine device,
  • Barrier methods (diaphragm, condom) with spermicide, or
  • Surgical sterilization (tubal ligation).
  • Participant must have OCA1B, as defined by ALL (a-d) of the following criteria:
  • Participant has ophthalmic signs or symptoms of albinism, including:
  • Bilateral visual acuity E-ETDRS EVA letter score of less than or equal to 83 (i.e., Snellen equivalent of 20/25 or worse) that is not attributable to any other pathology.
  • Bilateral iris transillumination that can be seen in clinical photographs.
  • Predominant contralateral decussation of ganglion cell axons, as determined by pattern visual evoked potential (VEP).
  • Participant has at least one definitive mutation in the OCA1 gene (tyrosinase).
  • Participant has no definitive mutations in the OCA2 gene.
  • EXCLUSION CRITERIA:
  • Participant is pregnant or breast-feeding.
  • Participant is a male AND has a definitive mutation in the OA1 gene.
  • Participant has any of the following abnormal laboratory test results:
  • Serum potassium \< 3.0 mEq/L,
  • Serum CK \> 500 U/L,
  • Hemoglobin \< 10.0 g/dL,
  • White blood cell (WBC) count \< 3.0 k/microL,
  • Plasma tyrosine \> 150 microM,
  • ESR \> 100 mm/h, and/or
  • Serum T4 \> 15 microg/dL OR Serum T4 \< 4 microg/dL.
  • Participant has keratopathy.
  • Participant has a current malignancy.
  • Participant has open skin lesions.
  • Participant is on a diet that deliberately increases protein intake to disproportionate levels (e.g., Atkins diet). The diet must be reasonably balanced, as determined by a dietician.
  • Participant has uncontrolled hypertension, defined as systolic blood pressure above 180 mmHg or diastolic blood pressure above 95 mmHg.
  • Participant has another chronic ocular disease that may confound the results of visual tests, such as age-related macular degeneration, cataract of possible visual significance, or uncontrolled glaucoma.
  • Participant drinks more than the equivalent of two glasses of wine per day on average, has a history of alcohol abuse, or has a severe liver illness.
  • Participant s liver is \> 3 cm below the right costal margin.
  • Participant has a muscle disease.
  • Participant is currently taking a medication known to cause elevated liver function tests including statins/HMG-Co-A reductase inhibitors (e.g., lovastatin, simvastatin); anti-epileptic medications (e.g., carbamazepine, phenytoin, phenobarbital); tetracycline or its derivatives, if used chronically; acetaminophen, if used daily/chronically; amiodarone; and any other medications with known significant liver toxicity.

Exclusion

    Key Trial Info

    Start Date :

    April 16 2013

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    February 7 2017

    Estimated Enrollment :

    5 Patients enrolled

    Trial Details

    Trial ID

    NCT01838655

    Start Date

    April 16 2013

    End Date

    February 7 2017

    Last Update

    February 26 2019

    Active Locations (1)

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    National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, United States, 20892