Trial reportMolecular genetics and metabolism2011
A 3-year randomized therapeutic trial of nitisinone in alkaptonuria.
Trial report in Molecular genetics and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01390077 (Nitisinone), which is not on this map. Cited by 91 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Nitisinone (NTBC) In Different Age Groups Of Patients With Alkaptonuria
Who cites it
91 citing papers in PubMed, 202 citations in OpenAlex.
- Radiological evolution of spinal disease in alkaptonuria and the effect of nitisinone.RMD open · 2022Trial
- Quantification of the flux of tyrosine pathway metabolites during nitisinone treatment of Alkaptonuria.Scientific reports · 2019Trial
- Patient-reported outcomes and functional assessments of patients with Alkaptonuria in a 3-year Nitisinone treatment trial.Molecular genetics and metabolismTrial
- Homogentisic Acid Disrupts the Blood-Brain Barrier and Promotes Aβ Aggregation in Alzheimer's Disease.Current medical science · 2026Article
- Case Report: Ochronotic arthropathy mimicking spondyloarthritis: a case-based review of diagnostic pitfalls and a novel likely pathogenic HGD variant.Frontiers in genetics · 2026Article
- Untargeted Metabolomics Reveals Metabolic Reprogramming Linked to HCC Risk in Late Diagnosed Tyrosinemia Type 1.Metabolites · 2025Article
- Article
- Harliku (nitisinone): first FDA-approved disease-modifying therapy for alkaptonuria.Annals of medicine and surgery (2012) · 2025Article
- Development of a radiographic vertebral severity score for evaluation of disease progression in alkaptonuria.Molecular genetics and metabolism · 2025Article
- Early-Onset Degenerative Bone Changes as a Manifestation of Alkaptonuria: A Case Report.Cureus · 2025Article
- Deep Learning Study of Alkaptonuria Spinal Disease Assesses Global and Regional Severity and Detects Occult Treatment Status.Journal of inherited metabolic disease · 2025Article
- Alkaptonuria: a rare disease with multiorgan manifestation and a long-awaited diagnosis.BMJ case reports · 2024Article
- Joint replacement risk is markedly increased in alkaptonuria (AKU) in those with prior arthroplasty.Molecular genetics and metabolism reports · 2024Article
- Ease of sutureless aortic valve replacement in a patient with unexpected ochronosis: a case report.Journal of cardiothoracic surgery · 2024Article
- Managing Alkaptonuria in Absence of Appropriate Medication: A Case Report and Review of Literature.Clinical medicine & research · 2024Review
- Alkaptonuria.Nature reviews. Disease primers · 2024Review
- First decade anniversary of the United Kingdom National Alkaptonuria Centre.JIMD reports · 2023Article
- A Previously Undiagnosed Case of Alkaptonuria in an 80-Year-Old Patient: A Case Report.Cureus · 2023Article
- Clinical development innovation in rare diseases: overcoming barriers to successful delivery of a randomised clinical trial in alkaptonuria-a mini-review.Orphanet journal of rare diseases · 2023Review
- Ochronotic arthropathy effectively treated with total hip and total knee arthroplasty: a case report.Frontiers in medicine · 2023Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Alkaptonuria is a rare, autosomal recessive disorder of tyrosine degradation due to deficiency of the third enzyme in the catabolic pathway. As a result, homogentisic acid (HGA) accumulates and is excreted in gram quantities in the urine, which turns dark upon alkalization. The first symptoms, occurring in early adulthood, involve a painful, progressively debilitating arthritis of the spine and large joints. Cardiac valvular disease and renal and prostate stones occur later. Previously suggested therapies have failed to show benefit, and management remains symptomatic. Nitisinone, a potent inhibitor of the second enzyme in the tyrosine catabolic pathway, is considered a potential therapy; proof-of-principle studies showed 95% reduction in urinary HGA. Based on those findings, a prospective, randomized clinical trial was initiated in 2005 to evaluate 40 patients over a 36-month period. The primary outcome parameter was hip total range of motion with measures of musculoskeletal function serving as secondary parameters. Biochemically, this study consistently demonstrated 95% reduction of HGA in urine and plasma over the course of 3 years. Clinically, primary and secondary parameters did not prove benefit from the medication. Side effects were infrequent. This trial illustrates the remarkable tolerability of nitisinone, its biochemical efficacy, and the need to investigate its use in younger individuals prior to development of debilitating arthritis.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.