Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Study of Alkaptonuria

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 7, 2016 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ) Identifier:
First received: June 13, 2000
Last updated: April 20, 2017
Last verified: October 7, 2016

The purpose of this study is to gain a better understanding of alkaptonuria and collect medical data on patients who may later participate in new drug trials for this rare genetic disease. In alkaptonuria, a pigment called homogentisic acid collects in bone and connective tissue, causing arthritis and eventually bone fractures, and also causes discoloration in the ears and whites of the eyes. Some patients also develop kidney stones and heart valve problems. Alkaptonuria has not been studied for decades; and scientists expect to gain comprehensive clinical information using current medical techniques.

Patients with alkaptonuria who are at least one month old may be eligible for this study. Participants will be evaluated at NIH s Clinical Center for 5 days every 2 to 3 years. They will have a medical history, physical examination, routine blood and urine tests. Blood may also be collected to measure a type of collagen that indicates new bone formation and to analyze DNA for genetic studies. 24-hour urine collections will be done to measure organic acids and homogentisic acid excretion, assess overall kidney function, and evaluate bone metabolism. A total of 89.5 ml (about 6 tablespoons) of blood will be drawn for these studies in adults and 51 ml (about 3 tablespoons) in children.

Patients will also have bone X-rays, kidney ultrasound, brain and chest computerized tomography (CT) scans, magnetic resonance imaging (MRI) scans of affected joints, electrocardiograms, echocardiogram, lung function tests, and a hearing test. Photographs of the face and full body (with underwear on) will be taken.

Patients will also have consultations with dentistry and ophthalmology, with physical therapy and rehabilitation medicine for arthritis management, and with cardiology for heart valve evaluation. When appropriate, patients may also have dermatology, pulmonology and neurology consultations.

The information from this study will enable doctors to better advise patients with alkaptonuria about their disease and treatment options. It will also prepare the way for clinical studies of a new drug that blocks production of homogentisic acid.


Study Type: Observational
Official Title: Clinical, Biochemical, and Molecular Investigations Into Alkaptonuria

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 200
Study Start Date: June 9, 2000
Detailed Description:
Alkaptonuria is a rare autosomal recessive disorder in which homogentisic acid accumulates and destroys connective tissue and bone, creating a condition called ochronosis. Symptoms generally begin in the third or fourth decade and progress to incapacitating spondylosis, arthropathy, and fractures by the sixth to eighth decades. Cardiac valve deterioration and renal and prostrate calculi also occur. Diagnosis is made by measurement of gram quantities of urinary homogentisic acid, which turns black on alkali treatment or exposure to oxygen. In the body, homogentisic acid forms a characteristic blue color in the cartilage of the ear and brown color in the sclera of the eye. The gene for homogentisic acid oxidase was isolated in 1996, and scores of different mutations have been defined. Only symptomatic treatment is available. We propose to investigate up to 200 alkaptonuric patients, particularly adults, during 5-day admissions, to define the disorder using current medical techniques. We will use our expertise in this disease to advise the population in terms of prognosis and therapy. Mutation analysis with correlation of genotype and phenotype, will be performed as a secondary goal. Finally, we will use this protocol to recruit patients into protocol 05-HG-0076. "Long-term Clinical Trial of Nitisinone in Alkaptonuria." Nitisinone is a very promising drug which inhibits the formation of homogentisic acid. The present protocol does not include treatment with nitisinone. Instead, we will examine patients, measure baseline excretion of homogentisic acid on repeated 24-hour urines, and characterize the signs and symptoms of alkaptonuria at different ages. This protocol will also serve as the "mother" protocol from which other alkaptonuria studies emanate.

Ages Eligible for Study:   2 Years to 90 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

All patients entering this study will carry the diagnosis of alkaptonuria, although we will confirm this diagnosis during the admission.


Patients will be excluded if they cannot travel to the NIH due to their medical condition, are less than two years old, or are in imminent danger of death due to, e.g., cardiac involvement.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00005909

Contact: Wendy J Introne, M.D. (301) 451-8879

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
National Human Genome Research Institute (NHGRI)
Principal Investigator: Wendy J Introne, M.D. National Human Genome Research Institute (NHGRI)
  More Information

Additional Information:
Responsible Party: National Human Genome Research Institute (NHGRI) Identifier: NCT00005909     History of Changes
Other Study ID Numbers: 000141
Study First Received: June 13, 2000
Last Updated: April 20, 2017

Keywords provided by National Institutes of Health Clinical Center (CC):
Homogentisic Acid
Inborn Error of Metabolism
Enzyme Defect
Homogentisic Acid Oxidase

Additional relevant MeSH terms:
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Pathologic Processes processed this record on April 21, 2017