OsteomalaciaNCT00099762
Catheterization to Locate Mesenchymal Tumors in Patients With Tumor-Induced Osteomalacia or Oncogenic Osteomalacia
An observational study of Osteomalacia and Neoplasms, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.
Trial summary
This study will use a procedure called selective venous catheterization in patients with tumor-induced osteomalacia (TIO) or oncogenic osteomalacia (OOM) to try to locate very small tumors that produce proteins called phosphatonins. Read more about this study
- Who is it for?
- Ages 8 to 100 years
- Conditions the study is for
- Osteomalacia, Neoplasms
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Dec 2004to 2 Sep 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
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 8 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have the clinical diagnosis of TIO/OOM to be considered for enrollment in this study. The diagnosis will be based upon a clinical history including some or all of: rickets (children), pathological fractures, bone pain, muscle weakness, low serum phosphorus with concomitant inappropriately high urine phosphorus, low or inappropriately low-normal serum vitamin 1,25 (OH)(2)-vitamin D3, and an elevated FGF-23 level in the absence of a family history of a phosphate wasting syndrome. Along with the clinical symptoms listed above, the patient must have undergone routine clinical imaging.
- Inclusion will be limited to all patients in whom a likely lesion was not localized by imaging, plus five patients for whom a likely lesion has been identified by imaging. Patients with a likely lesion identified will serve as positive controls.
- Patients must be able to give informed consent.
Who cannot join
- Patients with co-morbidities that would increase the risk of selective venous catheterization will be excluded from the study. This includes but is not limited to medical conditions such as: poorly controlled diabetes, renal insufficiency, chronic obstructive pulmonary disease, anemia, hypertension, clotting disorders, etc.
- Pregnancy is a contraindication to this venous catheterization procedure. A serum Beta-Hcg will be required for all eligible women of childbearing age unless documentation of a hysterectomy or other condition that makes pregnancy impossible is provided.
- Inability or unwillingness to give informed consent will exclude patients from this study. Female patients who will not allow pregnancy testing and will not provide documentation indicating a medical condition that makes pregnancy impossible will not be eligible for this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Selective Venous Catheterization for the Localization of Phosphaturic Mesenchymal Tumors
This study will use a procedure called selective venous catheterization in patients with tumor-induced osteomalacia (TIO) or oncogenic osteomalacia (OOM) to try to locate very small tumors that produce proteins called phosphatonins. Too much phosphatonin in the blood causes the kidneys to allow large amounts of phosphorus to be excreted in the urine, leading to low blood levels of phosphorus and, in turn, to osteomalacia (a condition of soft bones). Osteomalacia can cause bone fractures requiring many surgical procedures that can leave patients in pain. Patients may also feel weak and can lose height from massive bone loss. Selective venous catheterization is a way to measure the amount of phosphatonin in the blood and may be used as a way to locate phosphatonin-producing tumors that cannot be found using standard imaging techniques.
Patients with TIO or OOM are screened under NIDR Protocol 01-D-0184 with a medical history, review of medical records and routine physical examination. Other procedures may include blood tests, urine tests, and imaging tests, such as x-rays, bone densitometry, bone scan, computed tomography (CT) and magnetic resonance imaging (MRI). This study will include mostly patients whose tumors were not able to be located through imaging procedures, but also a few patients whose tumors were located.
Read more
All participants, regardless of whether or not their tumor was located, undergo selective venous catheterization. For this procedure, a radiologist inserts a catheter (thin flexible tube) into the body and uses fluoroscopy (a type of x-ray) to guide the tip of the catheter to different places in the body to collect small amounts of blood from the different areas. After the procedure, the patient lies flat for 2 hours and avoids moving his or her leg on the side where the catheter was placed.
The blood is analyzed to measure the amount phosphatonin is in each sample, and the amounts are compared to the average amount of phosphatonin in the general blood circulation. If a higher level of phosphatonin is found in one area and the location of the tumor is unknown, the patient undergoes imaging in that area. If a tumor is found and it is in an area where it can be removed surgically, the patient is given the option to have the surgery. If the tumor is not found by imaging done after the first catheterization procedure, the patient has the option to have a second catheterization, taking samples of blood only from the area where the phosphatonin was found to be the highest during the sampling procedure.
Read the detailed description
Phosphaturic mesenchymal tumors elaborate phosphate lowering factors (phosphatonins) which lead to tumor induced osteomalacia/osteogenic osteomalacia (TIO/OOM). Patients with TIO/OOM suffer years of significant morbidity and debilitation unless their tumors, which are notoriously difficult to locate, are removed.
Selective venous catheterization has been used to localize hormonally active neoplasms by demonstrating a gradient in the concentration of the hormone of interest between the vessel immediately draining the tumor site and the peripheral circulation. The primary objective of this protocol is to evaluate the utility of combining selective venous catheterization with biochemical assays that identify phosphatonins in the serum as a way to identify phosphatonin gradients and thereby localize phosphaturic tumors.
Our study population will consist of TIO/OOM patients with non-localized phosphaturic tumors as well as five patients whose lesions have been identified with some certainty by conventional imaging techniques. These individuals will undergo selective venous catheterization during which blood samples will be obtained and processed for the presence of phosphatonins. The primary endpoint will be met if a gradient indicating a possible tumor is found, focused clinical imaging in the appropriate anatomical sub-region identifies a lesion, and the lesion is confirmed to be a phosphaturic mesenchymal tumor upon surgical removal.
- Conditions
- Osteomalacia, Neoplasms
- Keywords
- Tumor Induced Osteomalacia, FGF-23, Phosphatonin, Hypophosphatemia, Oncogenic Osteomalacia, Phosphaturic Mesenchymal Tumor, TIO, Osteogenic Osteomalacia, OOM
- Medical subject headings
- Osteomalacia, Neoplasms, Oncogenic osteomalacia, Hypophosphatemia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2004 (estimated)
- Study start15 Dec 2004
- Primary completion2 Sep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for OsteomalaciaStudies 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
- Enrolment
- 45 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00099762
- Sponsor's protocol ID
- 050050
- Other IDs
- 05-D-0050
- Status last verified
- 2 Sep 2009
- First submitted
- 17 Dec 2004
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
ADHR Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000 Nov;26(3):345-8. doi: 10.1038/81664.
PubMed 11062477Berndt T, Craig TA, Bowe AE, Vassiliadis J, Reczek D, Finnegan R, Jan De Beur SM, Schiavi SC, Kumar R. Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent. J Clin Invest. 2003 Sep;112(5):785-94. doi: 10.1172/JCI18563.
PubMed 12952927Bowe AE, Finnegan R, Jan de Beur SM, Cho J, Levine MA, Kumar R, Schiavi SC. FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. Biochem Biophys Res Commun. 2001 Jun 22;284(4):977-81. doi: 10.1006/bbrc.2001.5084.
PubMed 11409890
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Selective Venous Catheterization for the Localization of Phosphaturic Mesenchymal Tumors
- ClinicalTrials.gov ID
- NCT00099762
- Acronym / sponsor ID
- 050050
- Conditions
- Osteomalacia, Neoplasms
- Keywords
- Tumor Induced Osteomalacia, FGF-23, Phosphatonin, Hypophosphatemia, Oncogenic Osteomalacia, Phosphaturic Mesenchymal Tumor, TIO, Osteogenic Osteomalacia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)US National Institutes of Health
- Study start
- 15 Dec 2004
- Primary completion
- 2 Sep 2009 (actual)
- First posted
- 20 Dec 2004 (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.
This study will use a procedure called selective venous catheterization in patients with tumor-induced osteomalacia (TIO) or oncogenic osteomalacia (OOM) to try to locate very small tumors that produce proteins called phosphatonins. Too much phosphatonin in the blood causes the kidneys to allow large amounts of phosphorus to be excreted in the urine, leading to low blood levels of phosphorus and, in turn, to osteomalacia (a condition of soft bones). Osteomalacia can cause bone fractures requiring many surgical procedures that can leave patients in pain. Patients may also feel weak and can lose height from massive bone loss. Selective venous catheterization is a way to measure the amount of phosphatonin in the blood and may be used as a way to locate phosphatonin-producing tumors that cannot be found using standard imaging techniques.
Patients with TIO or OOM are screened under NIDR Protocol 01-D-0184 with a medical history, review of medical records and routine physical examination. Other procedures may include blood tests, urine tests, and imaging tests, such as x-rays, bone densitometry, bone scan, computed tomography (CT) and magnetic resonance imaging (MRI). This study will include mostly patients whose tumors were not able to be located through imaging procedures, but also a few patients whose tumors were located.
All participants, regardless of whether or not their tumor was located, undergo selective venous catheterization. For this procedure, a radiologist inserts a catheter (thin flexible tube) into the body and uses fluoroscopy (a type of x-ray) to guide the tip of the catheter to different places in the body to collect small amounts of blood from the different areas. After the procedure, the patient lies flat for 2 hours and avoids moving his or her leg on the side where the catheter was placed.
The blood is analyzed to measure the amount phosphatonin is in each sample, and the amounts are compared to the average amount of phosphatonin in the general blood circulation. If a higher level of phosphatonin is found in one area and the location of the tumor is unknown, the patient undergoes imaging in that area. If a tumor is found and it is in an area where it can be removed surgically, the patient is given the option to have the surgery. If the tumor is not found by imaging done after the first catheterization procedure, the patient has the option to have a second catheterization, taking samples of blood only from the area where the phosphatonin was found to be the highest during the sampling procedure.
Detailed description
Phosphaturic mesenchymal tumors elaborate phosphate lowering factors (phosphatonins) which lead to tumor induced osteomalacia/osteogenic osteomalacia (TIO/OOM). Patients with TIO/OOM suffer years of significant morbidity and debilitation unless their tumors, which are notoriously difficult to locate, are removed.
Selective venous catheterization has been used to localize hormonally active neoplasms by demonstrating a gradient in the concentration of the hormone of interest between the vessel immediately draining the tumor site and the peripheral circulation. The primary objective of this protocol is to evaluate the utility of combining selective venous catheterization with biochemical assays that identify phosphatonins in the serum as a way to identify phosphatonin gradients and thereby localize phosphaturic tumors.
Our study population will consist of TIO/OOM patients with non-localized phosphaturic tumors as well as five patients whose lesions have been identified with some certainty by conventional imaging techniques. These individuals will undergo selective venous catheterization during which blood samples will be obtained and processed for the presence of phosphatonins. The primary endpoint will be met if a gradient indicating a possible tumor is found, focused clinical imaging in the appropriate anatomical sub-region identifies a lesion, and the lesion is confirmed to be a phosphaturic mesenchymal tumor upon surgical removal.
Study design
Who may qualify
- Ages
- 8 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Patients must have the clinical diagnosis of TIO/OOM to be considered for enrollment in this study. The diagnosis will be based upon a clinical history including some or all of: rickets (children), pathological fractures, bone pain, muscle weakness, low serum phosphorus with concomitant inappropriately high urine phosphorus, low or inappropriately low-normal serum vitamin 1,25 (OH)(2)-vitamin D3, and an elevated FGF-23 level in the absence of a family history of a phosphate wasting syndrome. Along with the clinical symptoms listed above, the patient must have undergone routine clinical imaging.
- Inclusion will be limited to all patients in whom a likely lesion was not localized by imaging, plus five patients for whom a likely lesion has been identified by imaging. Patients with a likely lesion identified will serve as positive controls.
- Patients must be able to give informed consent.
Key exclusion criteria (3 listed)
- Patients with co-morbidities that would increase the risk of selective venous catheterization will be excluded from the study. This includes but is not limited to medical conditions such as: poorly controlled diabetes, renal insufficiency, chronic obstructive pulmonary disease, anemia, hypertension, clotting disorders, etc.
- Pregnancy is a contraindication to this venous catheterization procedure. A serum Beta-Hcg will be required for all eligible women of childbearing age unless documentation of a hysterectomy or other condition that makes pregnancy impossible is provided.
- Inability or unwillingness to give informed consent will exclude patients from this study. Female patients who will not allow pregnancy testing and will not provide documentation indicating a medical condition that makes pregnancy impossible will not be eligible for this study.
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
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 11062477ADHR Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000 Nov;26(3):345-8. doi: 10.1038/81664.
- Background: PubMed 12952927Berndt T, Craig TA, Bowe AE, Vassiliadis J, Reczek D, Finnegan R, Jan De Beur SM, Schiavi SC, Kumar R. Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent. J Clin Invest. 2003 Sep;112(5):785-94. doi: 10.1172/JCI18563.
- Background: PubMed 11409890Bowe AE, Finnegan R, Jan de Beur SM, Cho J, Levine MA, Kumar R, Schiavi SC. FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. Biochem Biophys Res Commun. 2001 Jun 22;284(4):977-81. doi: 10.1006/bbrc.2001.5084.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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 Osteomalacia and Neoplasms, run by National Institute of Dental and Craniofacial Research (NIDCR) 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 3 inclusion and 3 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: finished, as of the sponsor's last update on 2 Jul 2017. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00099762, which also lists 3 linked publications.
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 2 Jul 2017.