Paget's Disease of BoneNCT02802384
Pathophysiology of Paget's Disease of Bone
An observational study of Paget's Disease of Bone, run by Johns Hopkins University at 1 site in United States.
Trial summary
Paget's disease of the bone is a skeletal disorder which results in increased and disorganized bone remodeling, leading to dense but fragile and expanding bones. The identified genetic causes of Paget's disease of bone only explain why bone is destroyed, but not why the bone formed in its place is abnormal. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Paget's Disease of Bone
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to Mar 2024
- 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 18 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adults with active Paget's Disease of Bone but without other medical conditions or use of medications known to directly affect the bone. Healthy controls similar to age and gender will also be recruited.
Who may be able to join
- Men and women between the ages of 18-99 years who have evidence of active Paget's disease of bone as clinically and/or radiographically defined by:
- Increased serum alkaline phosphatase or increased serum collagen type 1 c-telopeptide (CTX) or increase in urinary pyridinoline at diagnosis
- AND history of at least one of the following signs/symptoms: Pagetoid lesions(s) on x-ray/CT/MRI, increased uptake of radioactive substance by bone scan, bone pain, fracture, hearing loss, headache, hypercalcemia, or bony deformity.
- Men and women between the ages of 18-99 years who match age within 5 years of cases and gender who do NOT have evidence of Paget's disease of bone as defined by:
- No bone pain or bony deformity
- Normal serum alkaline phosphatase
Who cannot join
- Osteosarcoma or other blastic bony metastases alone
- Fibrous dysplasia of bone
- Hyperostosis frontalis interna
- All men and women < 18 years or > 99 years
- Pregnancy (women) determined by self-report
- Current use of oral contraceptive tablets or Depo-Provera™ (women)
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- Current use of hormone replacement therapy
- Creatinine clearance < 60 ml/min./1.73 m2 by Cockcroft-Gault based on most recent serum creatinine level (if greater than 1 year since last assessment, will be measured on collected blood sample to verify eligibility)
- Current smoking or tobacco use
- Alcohol use greater than 3 units daily
- Use of thiazolidinediones within the last year
- Use of medications known to impact bone and mineral metabolism, including use of a bisphosphonate in the last 11 months; ever use of teriparatide or denosumab; use of calcitonin, selective estrogen receptor modulators (SERMs), or estrogen within the past 6 months, prednisone > 5 mg for over 10 days in the last three months, anti-epileptic medications (e.g. phenytoin, carbamezapine, phenobarbitol, and primidone); current or use within the past year of aromatase inhibitors; leuprolide; histrelin
- History of a thyroid problem that is currently uncontrolled as defined by most recent thyroid stimulating hormone levels < 0.1 microIU/mL (if greater than 6 months since last assessment, will be measured on collected blood sample to verify eligibility)
- Other known metabolic or structural bone disease other than low bone density (e.g. hyperparathyroidism, multiple myeloma, sarcoid or other granulomatous disease, celiac disease, osteopetrosis, osteomalacia, osteitis fibrosa cystica)
- Other significant medical illness (heart disease, pulmonary disease, inflammatory bowel disease, malignancy other than ductal carcinoma in situ (DCIS) or non-melanoma skin cancer, rheumatologic conditions including rheumatoid arthritis, systemic lupus, renal disease requiring dialysis, etc.)
- Inability to understand and provide informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Investigation of Pathophysiology of Angiogenesis and Osteogenesis in Paget's Disease of Bone
Paget's disease of the bone is a skeletal disorder which results in increased and disorganized bone remodeling, leading to dense but fragile and expanding bones. The identified genetic causes of Paget's disease of bone only explain why bone is destroyed, but not why the bone formed in its place is abnormal.
Current treatment for people with Paget's disease of the bone is limited to patients with bone pain, thought to be related to high rate of bone turnover (breakdown and rebuilding of bone) and works by slowing down the rate of bone breakdown. The current treatment does not address the excess blood vessels and bone formed.
This research is being done to understand factors that may promote blood vessel and bone formation in Paget's disease of the bone.
Read the detailed description
The genetic mutations found in Paget's disease currently only account for about 15% of cases and are limited to genes that affect osteoclast differentiation and function. These mutations alone are insufficient to explain the full phenotype, particularly hypervascularity and increased bone formation. Through a series of basic science studies, the investigators have recently found that preosteoclasts secrete chemokines to promote migration of various stem cells, which then differentiate into osteoblasts and endothelial cells to support osteogenesis and angiogenesis, respectively.
The investigators will perform a cross sectional study of patients with active Paget's disease of bone compared to similar people without Paget's disease of bone. The goal is to enroll 10 patients with Paget's disease of the bone (cases) and 10 healthy, age- and sex-matched people (controls) whom meet similar exclusion criteria. Participants who consent to the study will undergo a brief history and physical exam, allow review of medical records relevant to their disease, and have one blood (5 tablespoons) sample drawn.
The investigators hypothesize that specific chemokine concentrations are increased in people with Paget's disease of the bone compared to controls. The investigators also hypothesize that these levels correlate with severity of disease. Therefore, the investigators primary objective is to determine if serum chemokine levels are increased in patients with Paget's disease of the bone. The secondary objective is to evaluate if the serum chemokine concentrations correlate with various markers of disease activity. Findings could aid in the clinical monitoring of patients with Paget's disease of the bone and could provide an additional therapeutic target to improve treatment of this painful disease.
- Conditions
- Paget's Disease of Bone
- Keywords
- Paget's Disease of Bone, Healthy controls
- Medical subject headings
- Osteitis Deformans
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 |
|---|---|---|
| Cases | People with active Paget's Disease of Bone | |
| Controls | Age and sex matched people without history of Paget's Disease of Bone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum chemokine level
Compare the serum chemokine concentrations in research participants with Paget's disease of bone to research participants without Paget's disease of bone
Measured: Day 1
Secondary outcomes (4)
Correlation of chemokine level to Paget's Disease of Bone Pain
Correlate the serum chemokine concentration in research participants with Paget's disease of bone to burden of disease as assessed clinically by pain utilizing the Likert pain scale.
Measured: Day 1
Correlation of chemokine level to alkaline phosphatase concentration
Correlate the serum chemokine concentration in research participants with Paget's disease of bone to burden of disease as assessed clinically by serum alkaline phosphatase concentration.
Measured: Day 1
Correlation of chemokine level to proportion of affected skeleton
Correlate the serum chemokine concentration in research participants with Paget's disease to percent of skeleton affected as assessed radiographically by bone scan and x-ray.
Measured: Day 1
Correlation of chemokine level to number of circulating stem cells
Correlate the serum chemokine concentration in research participants to number of circulating mesenchymal stem cell and epithelial progenitor cells.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2016 (estimated)
- Study startApr 2016
- Primary completionMar 2024
- Study completionMar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Paget's Disease of BoneStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Janet L Crane, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02802384
- Sponsor's protocol ID
- IRB00077130
- Status last verified
- Nov 2024
- First submitted
- 13 Jun 2016
- Last updated
- 20 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Pathophysiology of Angiogenesis and Osteogenesis in Paget's Disease of Bone
- ClinicalTrials.gov ID
- NCT02802384
- Acronym / sponsor ID
- IRB00077130
- Conditions
- Paget's Disease of Bone
- Keywords
- Paget's Disease of Bone, Healthy controls
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Apr 2016 (actual)
- Primary completion
- Mar 2024 (actual)
- Study completion
- Mar 2024 (actual)
- First posted
- 16 Jun 2016 (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.
Paget's disease of the bone is a skeletal disorder which results in increased and disorganized bone remodeling, leading to dense but fragile and expanding bones. The identified genetic causes of Paget's disease of bone only explain why bone is destroyed, but not why the bone formed in its place is abnormal.
Current treatment for people with Paget's disease of the bone is limited to patients with bone pain, thought to be related to high rate of bone turnover (breakdown and rebuilding of bone) and works by slowing down the rate of bone breakdown. The current treatment does not address the excess blood vessels and bone formed.
This research is being done to understand factors that may promote blood vessel and bone formation in Paget's disease of the bone.
Detailed description
The genetic mutations found in Paget's disease currently only account for about 15% of cases and are limited to genes that affect osteoclast differentiation and function. These mutations alone are insufficient to explain the full phenotype, particularly hypervascularity and increased bone formation. Through a series of basic science studies, the investigators have recently found that preosteoclasts secrete chemokines to promote migration of various stem cells, which then differentiate into osteoblasts and endothelial cells to support osteogenesis and angiogenesis, respectively.
The investigators will perform a cross sectional study of patients with active Paget's disease of bone compared to similar people without Paget's disease of bone. The goal is to enroll 10 patients with Paget's disease of the bone (cases) and 10 healthy, age- and sex-matched people (controls) whom meet similar exclusion criteria. Participants who consent to the study will undergo a brief history and physical exam, allow review of medical records relevant to their disease, and have one blood (5 tablespoons) sample drawn.
The investigators hypothesize that specific chemokine concentrations are increased in people with Paget's disease of the bone compared to controls. The investigators also hypothesize that these levels correlate with severity of disease. Therefore, the investigators primary objective is to determine if serum chemokine levels are increased in patients with Paget's disease of the bone. The secondary objective is to evaluate if the serum chemokine concentrations correlate with various markers of disease activity. Findings could aid in the clinical monitoring of patients with Paget's disease of the bone and could provide an additional therapeutic target to improve treatment of this painful disease.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cases | – | –People with active Paget's Disease of Bone |
| Controls | – | –Age and sex matched people without history of Paget's Disease of Bone |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with active Paget's Disease of Bone but without other medical conditions or use of medications known to directly affect the bone. Healthy controls similar to age and gender will also be recruited.
Key inclusion criteria (6 listed)
- Men and women between the ages of 18-99 years who have evidence of active Paget's disease of bone as clinically and/or radiographically defined by:
- Men and women between the ages of 18-99 years who match age within 5 years of cases and gender who do NOT have evidence of Paget's disease of bone as defined by:
Key exclusion criteria (16 listed)
- Osteosarcoma or other blastic bony metastases alone
- Fibrous dysplasia of bone
- Hyperostosis frontalis interna
- All men and women < 18 years or > 99 years
- Pregnancy (women) determined by self-report
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
Serum chemokine level
Time frame: Day 1
Compare the serum chemokine concentrations in research participants with Paget's disease of bone to research participants without Paget's disease of bone
4 secondary outcomes
Correlation of chemokine level to Paget's Disease of Bone Pain
Time frame: Day 1
Correlation of chemokine level to alkaline phosphatase concentration
Time frame: Day 1
Correlation of chemokine level to proportion of affected skeleton
Time frame: Day 1
Correlation of chemokine level to number of circulating stem cells
Time frame: Day 1
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 20 Nov 2024.
- Individual participant dataSharing planned: Undecided
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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.
Janet L Crane, M.D. principal investigator
Johns Hopkins University
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 Paget's Disease of Bone, run by Johns Hopkins University 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 6 inclusion and 16 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 20 Nov 2024. 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.
What does the primary outcome measure?
Serum chemokine level (time frame: Day 1). 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 20 Nov 2024.