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Long-Term Study of Nitisinone to Treat Alkaptonuria

NCT00107783 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 40

Last updated 2021-08-26

Study results available
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Summary

This 3-year study will examine the safety and effectiveness of long-term use of nitisinone (Orfadin) for treating joint problems in patients with alkaptonuria, an inherited disease in which a compound called homogentisic acid accumulates. The excess homogentisic acid causes arthritis and limited joint movement. It can also cause heart valve damage and kidney stones.

Patients between 30 and 80 years of age with alkaptonuria may be eligible for this study. Patients must have hip involvement, but at least one remaining hip joint. Candidates are recruited from among patients enrolled in protocol 00-HG-0141, "Clinical, Biochemical, and Molecular Investigations into Alkaptonuria." Participants may enter both protocols simultaneously.

Participants are randomly assigned to one of two treatment groups: one group takes their regular medicines plus a 2-mg nitisinone capsule daily; the other group takes only their regular medicines. Patients taking nitisinone have blood tests to measure liver function 2 weeks and 6 weeks after starting treatment. Before starting therapy, all patients are admitted to the NIH Clinical Center for 4-5 days to undergo the following procedures:

* Medical history and physical examination
* 24-hour urine collection to test for sugar, protein, and other molecules
* Blood tests for liver and thyroid function, blood counts, and blood chemistries
* Blood and urine tests to measure tyrosine and other amino acids and homogentisic acid
* Bone x-rays
* Spiral CT (computed tomography) of the abdomen to detect kidney stones
* Eye examination and evaluations by specialists in rehabilitation medicine and pain, plus other consults in skin, brain, lung, heart, and kidney, as needed

All patients, whether or not they receive nitisinone, return to the Clinical Center for a 2-3 day follow-up admission every 4 months for a history and physical examination, blood tests, and two 24-hour urine collections. Every 12 months (12, 24 and 36 months after starting the study), patients also have repeat bone x-rays, spiral CT, kidney ultrasound, echocardiogram, and electrocardiogram. An Magnetic Resonance Imaging (MRI) of the brain is done at the end of the study.

Sixteen months after the end of the study enrollment period, the treated and non-treated groups are evaluated. If nitisinone has delayed the progression of joint disease in the treated group, the study continues and all patients receive the drug for the remainder of the study. If not, the study continues for another 20 months, at which time the study ends and the evaluation process is repeated.

Patients who develop symptoms such as corneal crystals, pain, or severe liver or nervous system toxicity may be taken off the study.

Conditions

  • Alkaptonuria

Interventions

DRUG

Nitisinone (NTBC)

Treatment

Sponsors & Collaborators

  • National Human Genome Research Institute (NHGRI)

    lead NIH

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Model
PARALLEL

Eligibility

Min Age
30 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2005-01-31
Primary Completion
2009-04-30
Completion
2009-04-30

Countries

  • United States

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00107783 on ClinicalTrials.gov