Magnetic Resonance Imaging in High Risk Patients for the Development of Diffuse Idiopathic Skeletal Hyperostosis (DISH)

ID: NCT03237455
Status: Not yet recruiting
Phase: N/A
Start Date: April 01, 2018
First Submitted: July 30, 2017
Last Updated: February 22, 2018
Results: N/A
Sponsors & Collaborators: HaEmek Medical Center, Israel, The Chaim Sheba Medical Center
Location: Israel
Conditions: Hyperostosis, Diffuse Idiopathic Skeletal, Metabolic Syndrome, Diabetes Mellitus
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Study Description

Brief 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 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.
Condition or disease Intervention/treatment Phase

Diabetes Mellitus

Hyperostosis, Diffuse Idiopathic Skeletal

Metabolic Syndrome

Diagnostic Test: Thoracic spine x-rays+whole spine MRI
Other Names
imaging
Diagnostic Test: blood tests
Other Names
laboratory
Other: constitutional and demographic data collection
Other Names
data
N/A

Tracking Information

First Submitted DateJuly 30, 2017
Last Update Posted DateFebruary 22, 2018
Anticipated Start DateApril 01, 2018
Anticipated Completion DateNovember 30, 2018
Anticipated Primary Completion DateAugust 30, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • 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

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

Not Available

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleMagnetic Resonance Imaging in High Risk Patients for the Development of Diffuse Idiopathic Skeletal Hyperostosis (DISH)
Official TitleMagnetic Resonance Imaging in High Risk Patients for the Development of Diffuse Idiopathic Skeletal Hyperostosis (DISH)
Brief 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 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 TypeInterventional
Study PhaseN/A
Estimated Enrollment
30
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Single
Primary Purpose
Diagnostic
Conditions
Diabetes Mellitus
Hyperostosis, Diffuse Idiopathic Skeletal
Metabolic Syndrome
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Diagnostic Test: Thoracic spine x-rays+whole spine MRI

PA radiographs of the thoracic spine and MRI of the whole spine and sacroiliac joints

Other Names
imaging
Diagnostic Test: blood tests

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.

Other Names
laboratory
Other: constitutional and demographic data collection

demographics, concomitant diseases (in particular type 2 DM, hypertension, hyperlipidemia) concomitant medications, height and weight (BMI), waist circumference

Other Names
data
Study Groups/Cohorts
study group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection

control group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection

Study Arms
Active Comparator control group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection
Diagnostic Test : Thoracic spine x-rays+whole spine MRI
PA radiographs of the thoracic spine and MRI of the whole spine and sacroiliac joints

Active Comparator control group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection
Diagnostic Test : blood tests
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.

Active Comparator control group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection
Other : constitutional and demographic data collection
demographics, concomitant diseases (in particular type 2 DM, hypertension, hyperlipidemia) concomitant medications, height and weight (BMI), waist circumference

Experimental study group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection
Diagnostic Test : Thoracic spine x-rays+whole spine MRI
PA radiographs of the thoracic spine and MRI of the whole spine and sacroiliac joints

Experimental study group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection
Other : constitutional and demographic data collection
demographics, concomitant diseases (in particular type 2 DM, hypertension, hyperlipidemia) concomitant medications, height and weight (BMI), waist circumference

Experimental study group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection
Diagnostic Test : blood tests
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.

Arm Intervention/Treatment
Active Comparator control group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection
Diagnostic Test : Thoracic spine x-rays+whole spine MRI
Active Comparator control group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection
Diagnostic Test : blood tests
Active Comparator control group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection
Other : constitutional and demographic data collection
Experimental study group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection
Diagnostic Test : Thoracic spine x-rays+whole spine MRI
Experimental study group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection
Other : constitutional and demographic data collection
Experimental study group
Thoracic spine x-rays+whole spine MRI blood tests constitutional and demographic data collection
Diagnostic Test : blood tests

Recruitment Information

Recruitment Status:Not yet recruiting
Enrollment30
Completion DateNovember 30, 2018
Eligibility Criteria: Inclusion Criteria:
- Meet the NCEP 3 criteria for metabolic syndrome and/or have type 2 diabetes mellitus (9).
Age 40-49 years

Exclusion Criteria:
- 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
GenderAll
Age40 Years to 49 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
Contacts
Listed Location Countries
Israel

Administrative Information

NCT Number:NCT03237455
Other Study ID Numbers
0102-17-EMC
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible PartyReuven Mader, HaEmek Medical Center, Israel
Study Sponsor
HaEmek Medical Center, Israel
Collaborators
The Chaim Sheba Medical Center
Investigators
Principal Investigator
Reuven Mader, MD
HaEmek MC

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