AlkaptonuriaNCT00005909
Study of Alkaptonuria
An observational study of Alkaptonuria, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 2 to 115 years
- Conditions the study is for
- Alkaptonuria
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jun 2000to not given
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 115 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with confirmed or suspected alkaptonuria@@@
Who may be able to join
- All patients entering this study will carry the diagnosis of alkaptonuria, although we will confirm this diagnosis during the admission. Alkaptonuria has been reported to occur throughout the world, with concentrations in the Dominican Republic, Slovakia, and Germany. We plan to recruit patients of all ethnic backgrounds.
Who cannot join
- Patients will be excluded if they cannot travel to the NIH due to their medical condition or are in imminent danger of death due to, e.g., cardiac involvement. Children under two years of age are excluded because they are virtually never affected with the symptoms of this disorder, and their investigations can be delayed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: Clinical, Biochemical, and Molecular Investigations Into Alkaptonuria
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 two years of age may be eligible for this study. Participants will be evaluated at NIH s Clinical Center for 3 to 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.
Read more
Patients will (may) 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.
As medically indicated, 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.
Read the 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 prostate 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 300 alkaptonuria patients, particularly adults, every 2-3 years during 3-5 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 work to identify suitable clinical outcome measures that may be useful for future trials. The present protocol does not include treatment with nitisinone. Instead, we will examine patients, measure baseline excretion of homogentisic acid on 24-hour urine, and characterize the signs and symptoms of alkaptonuria at different ages.
- Conditions
- Alkaptonuria
- Keywords
- Homogentisic Acid, Ochronosis, Inborn Error of Metabolism, Arthritis, Enzyme Defect, Natural History, Alkaptonuria
- Medical subject headings
- Alkaptonuria, Ochronosis, Metabolism, Inborn Errors, Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Alkaptonuria | Patients with confirmed or suspected alkaptonuria |
What is being measured
The primary outcome is the main question the study is designed to answer.
To delineate the clinical and laboratory findings of alkaptonuria, using state-of-the-art medical technology such as cardiac CT, MRI, and echocardiograms.
To delineate the clinical and laboratory findings of alkaptonuria, using state-of-the-art medical technology such as cardiac CT, MRI, and echocardiograms.
Measured: Ongoing
Secondary outcomes (1)
To understand the natural history and rates of progression to identify suitable outcome measures for future studies.
To understand the natural history and rates of progression to identify suitable outcome measures for future studies.
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2000 (estimated)
- Study start21 Jun 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AlkaptonuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Wendy J Introne, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005909
- Sponsor's protocol ID
- 000141
- Other IDs
- 00-HG-0141
- Status last verified
- 12 May 2026
- First submitted
- 13 Jun 2000
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: This data will be deidentified.
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical, Biochemical, and Molecular Investigations Into Alkaptonuria
- ClinicalTrials.gov ID
- NCT00005909
- Acronym / sponsor ID
- 000141
- Conditions
- Alkaptonuria
- Keywords
- Homogentisic Acid, Ochronosis, Inborn Error of Metabolism, Arthritis, Enzyme Defect, Natural History, Alkaptonuria
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 21 Jun 2000 (actual)
- First posted
- 14 Jun 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 two years of age may be eligible for this study. Participants will be evaluated at NIH s Clinical Center for 3 to 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 (may) 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.
As medically indicated, 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.
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 prostate 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 300 alkaptonuria patients, particularly adults, every 2-3 years during 3-5 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 work to identify suitable clinical outcome measures that may be useful for future trials. The present protocol does not include treatment with nitisinone. Instead, we will examine patients, measure baseline excretion of homogentisic acid on 24-hour urine, and characterize the signs and symptoms of alkaptonuria at different ages.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alkaptonuria | – | –Patients with confirmed or suspected alkaptonuria |
Who may qualify
- Ages
- 2 to 115 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with confirmed or suspected alkaptonuria@@@
Key inclusion criteria (1 listed)
- All patients entering this study will carry the diagnosis of alkaptonuria, although we will confirm this diagnosis during the admission. Alkaptonuria has been reported to occur throughout the world, with concentrations in the Dominican Republic, Slovakia, and Germany. We plan to recruit patients of all ethnic backgrounds.
Key exclusion criteria (1 listed)
- Patients will be excluded if they cannot travel to the NIH due to their medical condition or are in imminent danger of death due to, e.g., cardiac involvement. Children under two years of age are excluded because they are virtually never affected with the symptoms of this disorder, and their investigations can be delayed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To delineate the clinical and laboratory findings of alkaptonuria, using state-of-the-art medical technology such as cardiac CT, MRI, and echocardiograms.
Time frame: Ongoing
To delineate the clinical and laboratory findings of alkaptonuria, using state-of-the-art medical technology such as cardiac CT, MRI, and echocardiograms.
1 secondary outcome
To understand the natural history and rates of progression to identify suitable outcome measures for future studies.
Time frame: Ongoing
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. This data will be deidentified.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Wendy J Introne, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alkaptonuria, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wendy J Introne, M.D. ((301) 451-8879, wi2p@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To delineate the clinical and laboratory findings of alkaptonuria, using state-of-the-art medical technology such as cardiac CT, MRI, and echocardiograms. (time frame: Ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.