Long-Term Study of Nitisinone to Treat Alkaptonuria
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 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Long-Term Clinical Trial of Nitisinone in Alkaptonuria|
- Change in Total ROM Worse Hip. [ Time Frame: Measured at baseline and at 36 months ] [ Designated as safety issue: No ]Change from baseline in the total (external + internal) hip range of motion (ROM) in the worse hip at 36 months.
- Change in Schober's Test [ Time Frame: Measured at baseline and at 36 months ] [ Designated as safety issue: No ]Change from baseline of Schober's test at 36 months. Schober's test measures a patient's ability to flex his/her lower back. The examiner makes a mark at L5 (fifth lumbar vertebra) and places one finger 5 cm below and another finger 10 cm above this mark. The patient is asked to touch his/her toes. The examiner measures the increase in distance between the two fingers.
- Change in Functional Reach Assessment [ Time Frame: Measured at baseline and at 36 months ] [ Designated as safety issue: No ]Change from baseline of functional reach assessment at 36 months. Functional reach assessment measures the difference between the length of a person's outstretched arm and their maximal reach forward, while maintaining balance.
- Change in Timed Get up and go [ Time Frame: Measured at baseline and at 36 months ] [ Designated as safety issue: No ]Change from baseline of timed get up and go at 36 months. In timed get up and go, the patient is asked to stand up from a standard chair and walk a distance of 3 meters, turn around and walk back to the chair and sit down. The examiner measures the time it takes for the patient to perform this series of tasks.
- Change in 6 Minute Walk Test (6MWT) [ Time Frame: Measured at baseline and at 36 months ] [ Designated as safety issue: No ]Change from baseline of the 6MWT at 36 months. The 6MWT measures the distance that a patient can quickly walk on a flat hard surface in a period of six minutes.
|Study Start Date:||January 2005|
|Study Completion Date:||April 2009|
|Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
No Intervention: Control
Subjects received nitisinone 2 mg orally, once daily.
Drug: Nitisinone (NTBC)
Other Name: Orfadin
Please refer to this study by its ClinicalTrials.gov identifier: NCT00107783
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|