Hyperostosis, Diffuse Idiopathic SkeletalNCT03237455
Magnetic Resonance Imaging in High Risk Patients for the Development of Diffuse Idiopathic Skeletal Hyperostosis (DISH)
A study testing Thoracic spine x-rays+whole spine MRI, blood tests and constitutional and demographic data collection in people with Hyperostosis, Diffuse Idiopathic Skeletal and Metabolic Syndrome, run by HaEmek Medical Center, Israel at 1 site in Israel.
Trial summary
Diffuse idiopathic skeletal hyperostosis (DISH) is a poorly understood, systemic condition characterized by progressive calcification and ossification of ligaments and entheses. The current classification criteria allow diagnosing the disease in its late course, when significant bony overgrowth already involves the… Read more about this study
- Who is it for?
- Ages 40 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperostosis, Diffuse Idiopathic Skeletal, Metabolic Syndrome, Diabetes Mellitus
- What is being tested?
- Thoracic spine x-rays+whole spine MRI, blood tests and constitutional and demographic data collection
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Aug 2018to 30 Dec 2022
- Phase
- Interventional
- 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 40 to 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Meet the NCEP 3 criteria for metabolic syndrome and/or have type 2 diabetes mellitus (9).
- Age 40-49 years
Who cannot join
- ESR and CRP levels above common levels adjusted for age, gender, and weight.(I have ref for the determination of common CRP levels).
- Positive HLA B-27 Personal or family history of Spondyloarthritis, psoriasis or inflammatory arthritis (past or present) Inflammatory back pain as defined by the ASAS definition (age at onset <40y, insidious onset, improvement with exercise, no improvement with rest, pain at night with improvement upon getting up = IBP if 4/5 items are present) (Ref) History of uveitis Plain radiographs with evidence for DISH
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
HaEmek MC and Chaim Sheba MC
Afula, 18101
Reuven Mader, MD, 972-4-6494354, mader_r@clalit.org.il
Irina Novofastovski, MD, 972-4-6494354, Irina_no@clalit.org.il
About this study
Diffuse idiopathic skeletal hyperostosis (DISH) is a poorly understood, systemic condition characterized by progressive calcification and ossification of ligaments and entheses. The current classification criteria allow diagnosing the disease in its late course, when significant bony overgrowth already involves the vertebral column and the appendicular skeleton. The research of the pathogenic mechanisms in DISH, is significantly hampered by the late diagnosis resulting from this definition.Based on recent MRI studies in both axial spondyloarthritis (axSpA) and in DISH, it seems that changes similar to the classical early inflammatory changes described in axSpA, can be detected in patients with DISH. We therefore hypothesize, that patients with metabolic syndrome without radiographic evidence for spinal DISH, might exhibit early MRI changes. If this hypothesis proves to be correct, early diagnosis and research of the possible pathogenetic mechanisms at this early stage might be very rewarding in investigations of the early aberrations of the entheses homeostasis and eventually early, more targeted therapeutic interventions. The study will examine MRI changes in patients, in their 5th decade of life, with high risk for the development of DISH (ie diabetes mellitus, metabolic syndrome) compared with patients who don't have this risk.
Read the detailed description
Patient's selection- Patients will be recruited from obesity/metabolic/diabetes clinics and from bariatric surgeries clinics. All patients will have the diagnosis of metabolic syndrome National Cholesterol Education Panel III (NCEP). Patients in their 5th decade of life will be recruited for the study. This study group will have to meet the NCEP 3 criteria for metabolic syndrome and/or have type 2 diabetes mellitus (9). An age and sex matched individuals who do not meet these pre-requisits will serve as a control group.
All asymptomatic patients will undergo postero-anterior and lateral x-rays of the thoracic spine, unless they have postero-anterior or lateral thoracic spine or chest x-rays in the year preceding the recruitment. For patients with back pain, addition of cervical or lumbar spine radiographs will be permitted based on the physician judgement. Patients recruited for the study will have a total spine and sacroiliac MRI (see below) read by radiologists and rheumatologists, expert in musculoskeletal imaging, who will be blinded for the patient's data. The readings of the radiographs and the MRI will be performed in a random order.
All patients and controls will undergo postero anterior and lateral thoracic spine X-rays and MRI of the entire spine and their sacroiliac joints (Spine: sagittal T1-weighted and T2 with fat suppression sequences, SIJ semicoronal T1-weighted and T2 with fat suppression sequences) at study entry.
An accepted scoring system for the interpretation of the MRI studies will be employed for both the spine and the sacroiliac joints.
- Being tested
- Thoracic spine x-rays+whole spine MRI, blood tests, constitutional and demographic data collection
- Medical subject headings
- Hyperostosis, Diffuse Idiopathic Skeletal, Metabolic Syndrome, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thoracic spine x-rays+whole spine MRIDiagnostic test
Also called imaging
PA radiographs of the thoracic spine and MRI of the whole spine and sacroiliac joints
blood testsDiagnostic test
Also called laboratory
blood chemistry including total cholesterol, LDL HDL, CBC, HbA1C, fasting glucose, TG, and insulin levels, HLA-B27, 2 vials of frozen serum for future studies.
constitutional and demographic data collectionOther
Also called data
demographics, concomitant diseases (in particular type 2 DM, hypertension, hyperlipidemia) concomitant medications, height and weight (BMI), waist circumference
| Study group | Role | What they receive |
|---|---|---|
| study group | Experimental | Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection Receives: Diagnostic Test: Thoracic spine x-rays+whole spine MRI; Diagnostic Test: blood tests; Other: constitutional and demographic data collection |
| control group | Active comparator | Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection Receives: Diagnostic Test: Thoracic spine x-rays+whole spine MRI; Diagnostic Test: blood tests; Other: constitutional and demographic data collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inflammatory changes in the spine and/or sacroiliac joints
inflammatory bone marrow edema lesions and fatty lesions and the anterior and posterior corners of the spine (Berlin score) as well as for the presence of enthesitis on the posterior elements.
The sacroiliac joints will also be scored according to the Berlin scoring method for the presence of acute and structural inflammatory lesion, including BME, fat metaplasia, erosions, sclerosis, ankylosis. Anterior and posterior extraarticular enthesitis will also be registered
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2017
- Study start1 Aug 2018
- Primary completion30 Dec 2022 (estimated)
- Study completion30 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Hyperostosis, Diffuse Idiopathic SkeletalStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- case control study
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- HaEmek Medical Center, Israel
- Sponsor type
- University, hospital or other
- Collaborators
- The Chaim Sheba Medical Center
- Responsible party
- Principal investigator, Reuven Mader, HaEmek Medical Center, Israel
- Investigators
- Reuven Mader, MD, Principal investigator, HaEmek MC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03237455
- Sponsor's protocol ID
- 0102-17-EMC
- Status last verified
- Aug 2022
- First submitted
- 30 Jul 2017
- Last updated
- 9 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Other researchers are expected to perform the study in their own countries. If they perform the study, unidentified data from the present study will be processed with the other parties data.
Publications
Mader R, Verlaan JJ, Buskila D. Diffuse idiopathic skeletal hyperostosis: clinical features and pathogenic mechanisms. Nat Rev Rheumatol. 2013 Dec;9(12):741-50. doi: 10.1038/nrrheum.2013.165. Epub 2013 Nov 5.
PubMed 24189840Mader R, Novofestovski I, Adawi M, Lavi I. Metabolic syndrome and cardiovascular risk in patients with diffuse idiopathic skeletal hyperostosis. Semin Arthritis Rheum. 2009 Apr;38(5):361-5. doi: 10.1016/j.semarthrit.2008.01.010. Epub 2008 Mar 4.
PubMed 18304611Mader R, Buskila D, Verlaan JJ, Atzeni F, Olivieri I, Pappone N, Di Girolamo C, Sarzi-Puttini P. Developing new classification criteria for diffuse idiopathic skeletal hyperostosis: back to square one. Rheumatology (Oxford). 2013 Feb;52(2):326-30. doi: 10.1093/rheumatology/kes257. Epub 2012 Sep 29.
PubMed 23024057Weiss BG, Bachmann LM, Pfirrmann CW, Kissling RO, Zubler V. Whole Body Magnetic Resonance Imaging Features in Diffuse Idiopathic Skeletal Hyperostosis in Conjunction with Clinical Variables to Whole Body MRI and Clinical Variables in Ankylosing Spondylitis. J Rheumatol. 2016 Feb;43(2):335-42. doi: 10.3899/jrheum.150162. Epub 2015 Dec 15.
PubMed 26669910Mader R, Novofastovski I, Iervolino S, Pavlov A, Chervinsky L, Schwartz N, Pappone N. Ultrasonography of peripheral entheses in the diagnosis and understanding of diffuse idiopathic skeletal hyperostosis (DISH). Rheumatol Int. 2015 Mar;35(3):493-7. doi: 10.1007/s00296-014-3190-0. Epub 2014 Dec 13.
PubMed 25503650Arad U, Elkayam O, Eshed I. Magnetic resonance imaging in diffuse idiopathic skeletal hyperostosis: similarities to axial spondyloarthritis. Clin Rheumatol. 2017 Jul;36(7):1545-1549. doi: 10.1007/s10067-017-3617-6. Epub 2017 Mar 31.
PubMed 28364275Julkunen H, Heinonen OP, Pyorala K. Hyperostosis of the spine in an adult population. Its relation to hyperglycaemia and obesity. Ann Rheum Dis. 1971 Nov;30(6):605-12. doi: 10.1136/ard.30.6.605. No abstract available.
PubMed 51301408. Mader R, Fawaz A, Bieber A, Novofastovski I. Diffuse idiopathic skeletal hyperostosis (DISH) of young adults: lessons to be learnt. Austin J Orthopade & Rheumatol. 2016; 3(4): 1043.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001 May 16;285(19):2486-97. doi: 10.1001/jama.285.19.2486. No abstract available.
PubMed 11368702Landewe RB, Hermann KG, van der Heijde DM, Baraliakos X, Jurik AG, Lambert RG, Ostergaard M, Rudwaleit M, Salonen DC, Braun J. Scoring sacroiliac joints by magnetic resonance imaging. A multiple-reader reliability experiment. J Rheumatol. 2005 Oct;32(10):2050-5.
PubMed 16206369
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Magnetic Resonance Imaging in High Risk Patients for the Development of Diffuse Idiopathic Skeletal Hyperostosis (DISH)
- ClinicalTrials.gov ID
- NCT03237455
- Acronym / sponsor ID
- 0102-17-EMC
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- HaEmek Medical Center, IsraelUniversity, hospital or other
- Collaborators
- The Chaim Sheba Medical Center
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 30 Dec 2022 (estimated)
- Study completion
- 30 Dec 2022 (estimated)
- First posted
- 2 Aug 2017 (actual)
- 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.
Diffuse idiopathic skeletal hyperostosis (DISH) is a poorly understood, systemic condition characterized by progressive calcification and ossification of ligaments and entheses. The current classification criteria allow diagnosing the disease in its late course, when significant bony overgrowth already involves the vertebral column and the appendicular skeleton. The research of the pathogenic mechanisms in DISH, is significantly hampered by the late diagnosis resulting from this definition.Based on recent MRI studies in both axial spondyloarthritis (axSpA) and in DISH, it seems that changes similar to the classical early inflammatory changes described in axSpA, can be detected in patients with DISH. We therefore hypothesize, that patients with metabolic syndrome without radiographic evidence for spinal DISH, might exhibit early MRI changes. If this hypothesis proves to be correct, early diagnosis and research of the possible pathogenetic mechanisms at this early stage might be very rewarding in investigations of the early aberrations of the entheses homeostasis and eventually early, more targeted therapeutic interventions. The study will examine MRI changes in patients, in their 5th decade of life, with high risk for the development of DISH (ie diabetes mellitus, metabolic syndrome) compared with patients who don't have this risk.
Detailed description
Patient's selection- Patients will be recruited from obesity/metabolic/diabetes clinics and from bariatric surgeries clinics. All patients will have the diagnosis of metabolic syndrome National Cholesterol Education Panel III (NCEP). Patients in their 5th decade of life will be recruited for the study. This study group will have to meet the NCEP 3 criteria for metabolic syndrome and/or have type 2 diabetes mellitus (9). An age and sex matched individuals who do not meet these pre-requisits will serve as a control group.
All asymptomatic patients will undergo postero-anterior and lateral x-rays of the thoracic spine, unless they have postero-anterior or lateral thoracic spine or chest x-rays in the year preceding the recruitment. For patients with back pain, addition of cervical or lumbar spine radiographs will be permitted based on the physician judgement. Patients recruited for the study will have a total spine and sacroiliac MRI (see below) read by radiologists and rheumatologists, expert in musculoskeletal imaging, who will be blinded for the patient's data. The readings of the radiographs and the MRI will be performed in a random order.
All patients and controls will undergo postero anterior and lateral thoracic spine X-rays and MRI of the entire spine and their sacroiliac joints (Spine: sagittal T1-weighted and T2 with fat suppression sequences, SIJ semicoronal T1-weighted and T2 with fat suppression sequences) at study entry.
An accepted scoring system for the interpretation of the MRI studies will be employed for both the spine and the sacroiliac joints.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- case control study
| Arm | Type | Receives |
|---|---|---|
| study group | Experimental | Diagnostic Test: Thoracic spine x-rays+whole spine MRI, Diagnostic Test: blood tests, Other: constitutional and demographic data collectionThoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection |
| control group | Active comparator | Diagnostic Test: Thoracic spine x-rays+whole spine MRI, Diagnostic Test: blood tests, Other: constitutional and demographic data collectionThoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection |
Who may qualify
- Ages
- 40 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Meet the NCEP 3 criteria for metabolic syndrome and/or have type 2 diabetes mellitus (9).
- Age 40-49 years
Key exclusion criteria (2 listed)
- ESR and CRP levels above common levels adjusted for age, gender, and weight.(I have ref for the determination of common CRP levels).
- Positive HLA B-27 Personal or family history of Spondyloarthritis, psoriasis or inflammatory arthritis (past or present) Inflammatory back pain as defined by the ASAS definition (age at onset <40y, insidious onset, improvement with exercise, no improvement with rest, pain at night with improvement upon getting up = IBP if 4/5 items are present) (Ref) History of uveitis Plain radiographs with evidence for DISH
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thoracic spine x-rays+whole spine MRIAlso: imagingPA radiographs of the thoracic spine and MRI of the whole spine and sacroiliac joints | Diagnostic test | control group, study group |
| blood testsAlso: laboratoryblood chemistry including total cholesterol, LDL HDL, CBC, HbA1C, fasting glucose, TG, and insulin levels, HLA-B27, 2 vials of frozen serum for future studies. | Diagnostic test | control group, study group |
| constitutional and demographic data collectionAlso: datademographics, concomitant diseases (in particular type 2 DM, hypertension, hyperlipidemia) concomitant medications, height and weight (BMI), waist circumference | Other | control group, study group |
Primary outcome
Inflammatory changes in the spine and/or sacroiliac joints
Time frame: 6 months
inflammatory bone marrow edema lesions and fatty lesions and the anterior and posterior corners of the spine (Berlin score) as well as for the presence of enthesitis on the posterior elements. The sacroiliac joints will also be scored according to the Berlin scoring method for the presence of acute and structural inflammatory lesion, including BME, fat metaplasia, erosions, sclerosis, ankylosis. Anterior and posterior extraarticular enthesitis will also be registered
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2022.
- Background: PubMed 24189840Mader R, Verlaan JJ, Buskila D. Diffuse idiopathic skeletal hyperostosis: clinical features and pathogenic mechanisms. Nat Rev Rheumatol. 2013 Dec;9(12):741-50. doi: 10.1038/nrrheum.2013.165. Epub 2013 Nov 5.
- Background: PubMed 18304611Mader R, Novofestovski I, Adawi M, Lavi I. Metabolic syndrome and cardiovascular risk in patients with diffuse idiopathic skeletal hyperostosis. Semin Arthritis Rheum. 2009 Apr;38(5):361-5. doi: 10.1016/j.semarthrit.2008.01.010. Epub 2008 Mar 4.
- Background: PubMed 23024057Mader R, Buskila D, Verlaan JJ, Atzeni F, Olivieri I, Pappone N, Di Girolamo C, Sarzi-Puttini P. Developing new classification criteria for diffuse idiopathic skeletal hyperostosis: back to square one. Rheumatology (Oxford). 2013 Feb;52(2):326-30. doi: 10.1093/rheumatology/kes257. Epub 2012 Sep 29.
- Background: PubMed 26669910Weiss BG, Bachmann LM, Pfirrmann CW, Kissling RO, Zubler V. Whole Body Magnetic Resonance Imaging Features in Diffuse Idiopathic Skeletal Hyperostosis in Conjunction with Clinical Variables to Whole Body MRI and Clinical Variables in Ankylosing Spondylitis. J Rheumatol. 2016 Feb;43(2):335-42. doi: 10.3899/jrheum.150162. Epub 2015 Dec 15.
- Background: PubMed 25503650Mader R, Novofastovski I, Iervolino S, Pavlov A, Chervinsky L, Schwartz N, Pappone N. Ultrasonography of peripheral entheses in the diagnosis and understanding of diffuse idiopathic skeletal hyperostosis (DISH). Rheumatol Int. 2015 Mar;35(3):493-7. doi: 10.1007/s00296-014-3190-0. Epub 2014 Dec 13.
- Background: PubMed 28364275Arad U, Elkayam O, Eshed I. Magnetic resonance imaging in diffuse idiopathic skeletal hyperostosis: similarities to axial spondyloarthritis. Clin Rheumatol. 2017 Jul;36(7):1545-1549. doi: 10.1007/s10067-017-3617-6. Epub 2017 Mar 31.
- Background: PubMed 5130140Julkunen H, Heinonen OP, Pyorala K. Hyperostosis of the spine in an adult population. Its relation to hyperglycaemia and obesity. Ann Rheum Dis. 1971 Nov;30(6):605-12. doi: 10.1136/ard.30.6.605. No abstract available.
- Background8. Mader R, Fawaz A, Bieber A, Novofastovski I. Diffuse idiopathic skeletal hyperostosis (DISH) of young adults: lessons to be learnt. Austin J Orthopade & Rheumatol. 2016; 3(4): 1043.
- Background: PubMed 11368702Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001 May 16;285(19):2486-97. doi: 10.1001/jama.285.19.2486. No abstract available.
- Background: PubMed 16206369Landewe RB, Hermann KG, van der Heijde DM, Baraliakos X, Jurik AG, Lambert RG, Ostergaard M, Rudwaleit M, Salonen DC, Braun J. Scoring sacroiliac joints by magnetic resonance imaging. A multiple-reader reliability experiment. J Rheumatol. 2005 Oct;32(10):2050-5.
- Individual participant dataSharing planned: No. Other researchers are expected to perform the study in their own countries. If they perform the study, unidentified data from the present study will be processed with the other parties data.
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.
Reuven Mader, MD principal investigator
HaEmek MC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Thoracic spine x-rays+whole spine MRI, blood tests and constitutional and demographic data collection in people with Hyperostosis, Diffuse Idiopathic Skeletal and Metabolic Syndrome, run by HaEmek Medical Center, Israel at 1 site in Israel.
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 2 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 9 Aug 2022. 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 Israel. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Reuven Mader, MD (972-4-6494354, mader_r@clalit.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Inflammatory changes in the spine and/or sacroiliac joints (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03237455, which also lists 10 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 9 Aug 2022; AzTrials last refreshed its copy on 2 Nov 2026.