<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02967042</url>
  </required_header>
  <id_info>
    <org_study_id>T239/2016</org_study_id>
    <nct_id>NCT02967042</nct_id>
  </id_info>
  <brief_title>Chronic Kidney Disease and Bone - Correlation Between 18F-PET-TT Imaging and Histomorphometry of Bone in CKD Patients</brief_title>
  <acronym>CKD-Bone</acronym>
  <official_title>Chronic Kidney Disease and Bone - Correlation Between 18F-PET-TT Imaging and Histomorphometry of Bone in Patients With Chronic Kidney Disease and Secondary Hyperparathyroidism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Turku University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Turku University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chronic kidney disease (CKD) is an increasing public health problem and the number of patient&#xD;
      with chronic kidney disease is increasing worldwide. Bone abnormalities are found almost&#xD;
      universally in patients with CKD requiring dialysis and in the majority of patients with CKD&#xD;
      stages 3-5. Chronic kidney disease-mineral bone disorder (CKD-MBD) is a complex disorder of&#xD;
      bone and mineral metabolism, which is associated with disorder in circulating levels of&#xD;
      hormones and development of secondary hyperparathyroid disease. The abnormalities of mineral&#xD;
      homeostasis impair bone remodeling and mineralization and results in cortical and trabecular&#xD;
      defects and an increased fracture risk. There is also an association with increased morbidity&#xD;
      and mortality. CKD-MBD is also associated with development of calcification of the blood&#xD;
      vessels. During the last decade it has been increasingly acknowledged that mineral and bone&#xD;
      disorder contribute to the excessively high cardiovascular morbidity and mortality in&#xD;
      patients with chronic kidney disease.&#xD;
&#xD;
      The diagnosis of mineral bone disorder and the underlying bone histology in CKD patients is&#xD;
      challenging. The treatment of renal osteodystrophy (ROD) and especially the treatment of&#xD;
      fractures in this patient group, depends on the underlying bone histopathology and bone&#xD;
      turnover. The gold standard for diagnosing the subtypes of ROD is bone biopsy, but it is&#xD;
      invasive and requires considerable expertise regarding quantitative histomorphometry and&#xD;
      interpretation. Plasma parathormone (PTH) measurement is commonly used to evaluate these&#xD;
      patients, and generally extremely high or low PTH levels predict the underlying bone&#xD;
      disorder. Still PTHs ability to correctly estimate turnover in bone is limited. Several&#xD;
      biomarkers such as tartrate-resistant acid phosphatase 5b (TRAP5b) and procollagen type 1&#xD;
      N-terminal propetide (PINP) has been investigated, but no biomarker in clinical use has yet&#xD;
      been proven suitable or superior to PTH to estimate overall bone histology.&#xD;
&#xD;
      18F-NaF positron emission tomography (18F-NaF PET) is a noninvasive quantitative imaging&#xD;
      technique that allows assessment of regional bone turnover at clinically relevant sites.&#xD;
      18F-NaF is a bone-seeking tracer, which reflects remodeling of bone and osteoblast&#xD;
      activity25. 18F-NaF serves as an efficient tracer to measure metabolic changes in bone. A&#xD;
      correlation between histomorphometric markers such as bone formation rate (BFR) and tracer&#xD;
      activity in the 18F- NaF PET scan in CKD patients has previously been shown in one small&#xD;
      study.&#xD;
&#xD;
      This study's goal is to evaluate, if 18-NaF-Positron emission tomography-computed tomography&#xD;
      (18F-PET-TT) can be used in the assessment of CKD patients. The hypothesis is that 18F-PET-TT&#xD;
      correlates with the histomorphometry of bone biopsy and with the calcification score in CKD&#xD;
      patients and that 18F-PET-TT maybe can be used as a diagnostic imaging technique in the&#xD;
      future.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a cross-sectional prospective study. 10 - 20 patients with secondary/tertiary&#xD;
      hyprparathyreoidism on oeritoneal dialysis, hemodialysis, predialysis patients and patients,&#xD;
      who have received a kidney transplant will be included,. Data collection in the dialysis&#xD;
      group is finnished and the first article published (Aaltonen et al, Bone 2020). A control&#xD;
      group was recruited for validation of the PET-method.&#xD;
&#xD;
      All participants undergo a 18F-PET-TT scan. PET, with the short half-life bone seeking&#xD;
      18F-Sodium Fluoride (18F-NaF), provide an unique way of assessment of regional bone&#xD;
      metabolism. 18F-NaF binds to sights of new bone formation and serves as a marker of bone&#xD;
      blood flow and osteoblastic activity. A dynamic 18F-PET-TT imaging is first done of the&#xD;
      lumbar region of the spine, following with a static PET-TT and also measurement of&#xD;
      calcification score using PET-TT. 18F-NaF is injected intravenously by direct venipuncture or&#xD;
      intravenous catheter. All the patients are also asked for permission to use DNA-samples if&#xD;
      needed.&#xD;
&#xD;
      Blood tests measuring the bone formation and turnover will be taken during the normal&#xD;
      clinical controls of the patients or at the latest wheb the bone biopsy is takekn.&#xD;
      Echocardiogram, which is reasonable sensitive, is done to detect and evaluate valvular&#xD;
      calcification. Bone biopsy is done in the day care unit within one month from the PET-scan.&#xD;
      To obtain information about dynamic parameters of the bone, the patients had double labeling&#xD;
      with tetracycline. The biopsy is taken in local anesthesia from the anterior iliac spine&#xD;
      vertically.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 17, 2016</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evidence of kidney patients adynamic or hyperdynamic bone disease assessed by 18F-PET-TT</measure>
    <time_frame>3 years</time_frame>
    <description>18F-PET correlates with histomorphometric markers in bone biopsy</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Chronic Kidney Disease</condition>
  <arm_group>
    <arm_group_label>18F-PET-TT</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>18F-PET-TT</intervention_name>
    <description>can 18F-PET-TT be used as an diagnostic tool in patients with CKD-MBD</description>
    <arm_group_label>18F-PET-TT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with severely decreased kidney function (eGRF below 20ml/min) with secondary&#xD;
             hyperparathyroidism. In addition a group of healthy volunteers.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy, parathyroidectomy, biphosphonate-medication.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>95 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kaj Metsärinne, LT</last_name>
    <role>Study Director</role>
    <affiliation>Senior physician /TYKS - nefrologia ja dialyysihoidot</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Louise Aaltonen, LL</last_name>
    <phone>023138003</phone>
    <email>louise.aaltonen@tyks.fi</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Niina Koivuviita, LT</last_name>
    <email>Niina.Koivuviita@tyks.fi</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>TYKS/nefrologia ja dialyysihoidot</name>
      <address>
        <city>Turku</city>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Louise Aaltonen, LL</last_name>
      <phone>023138003</phone>
      <email>louise.aaltonen@tyks.fi</email>
    </contact>
    <investigator>
      <last_name>Louise Aaltonen, LL</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <link>
    <url>https://doi.org/10.1016/j.bone.2020.115267</url>
    <description>Correlation between 18F-Sodium Fluoride positron emission tomography and bone histomorphometry in dialysis patients</description>
  </link>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>September 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 17, 2016</study_first_posted>
  <last_update_submitted>May 11, 2020</last_update_submitted>
  <last_update_submitted_qc>May 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02967042
org study id: T239/2016
nct id: NCT02967042
lead sponsor: 
has dmc: Yes
Chronic kidney disease (CKD) is an increasing public health problem and the number of patient
      with chronic kidney disease is increasing worldwide. Bone abnormalities are found almost
      universally in patients with CKD requiring dialysis and in the majority of patients with CKD
      stages 3-5. Chronic kidney disease-mineral bone disorder (CKD-MBD) is a complex disorder of
      bone and mineral metabolism, which is associated with disorder in circulating levels of
      hormones and development of secondary hyperparathyroid disease. The abnormalities of mineral
      homeostasis impair bone remodeling and mineralization and results in cortical and trabecular
      defects and an increased fracture risk. There is also an association with increased morbidity
      and mortality. CKD-MBD is also associated with development of calcification of the blood
      vessels. During the last decade it has been increasingly acknowledged that mineral and bone
      disorder contribute to the excessively high cardiovascular morbidity and mortality in
      patients with chronic kidney disease.

      The diagnosis of mineral bone disorder and the underlying bone histology in CKD patients is
      challenging. The treatment of renal osteodystrophy (ROD) and especially the treatment of
      fractures in this patient group, depends on the underlying bone histopathology and bone
      turnover. The gold standard for diagnosing the subtypes of ROD is bone biopsy, but it is
      invasive and requires considerable expertise regarding quantitative histomorphometry and
      interpretation. Plasma parathormone (PTH) measurement is commonly used to evaluate these
      patients, and generally extremely high or low PTH levels predict the underlying bone
      disorder. Still PTHs ability to correctly estimate turnover in bone is limited. Several
      biomarkers such as tartrate-resistant acid phosphatase 5b (TRAP5b) and procollagen type 1
      N-terminal propetide (PINP) has been investigated, but no biomarker in clinical use has yet
      been proven suitable or superior to PTH to estimate overall bone histology.

      18F-NaF positron emission tomography (18F-NaF PET) is a noninvasive quantitative imaging
      technique that allows assessment of regional bone turnover at clinically relevant sites.
      18F-NaF is a bone-seeking tracer, which reflects remodeling of bone and osteoblast
      activity25. 18F-NaF serves as an efficient tracer to measure metabolic changes in bone. A
      correlation between histomorphometric markers such as bone formation rate (BFR) and tracer
      activity in the 18F- NaF PET scan in CKD patients has previously been shown in one small
      study.

      This study's goal is to evaluate, if 18-NaF-Positron emission tomography-computed tomography
      (18F-PET-TT) can be used in the assessment of CKD patients. The hypothesis is that 18F-PET-TT
      correlates with the histomorphometry of bone biopsy and with the calcification score in CKD
      patients and that 18F-PET-TT maybe can be used as a diagnostic imaging technique in the
      future.
This is a cross-sectional prospective study. 10 - 20 patients with secondary/tertiary
      hyprparathyreoidism on oeritoneal dialysis, hemodialysis, predialysis patients and patients,
      who have received a kidney transplant will be included,. Data collection in the dialysis
      group is finnished and the first article published (Aaltonen et al, Bone 2020). A control
      group was recruited for validation of the PET-method.

      All participants undergo a 18F-PET-TT scan. PET, with the short half-life bone seeking
      18F-Sodium Fluoride (18F-NaF), provide an unique way of assessment of regional bone
      metabolism. 18F-NaF binds to sights of new bone formation and serves as a marker of bone
      blood flow and osteoblastic activity. A dynamic 18F-PET-TT imaging is first done of the
      lumbar region of the spine, following with a static PET-TT and also measurement of
      calcification score using PET-TT. 18F-NaF is injected intravenously by direct venipuncture or
      intravenous catheter. All the patients are also asked for permission to use DNA-samples if
      needed.

      Blood tests measuring the bone formation and turnover will be taken during the normal
      clinical controls of the patients or at the latest wheb the bone biopsy is takekn.
      Echocardiogram, which is reasonable sensitive, is done to detect and evaluate valvular
      calcification. Bone biopsy is done in the day care unit within one month from the PET-scan.
      To obtain information about dynamic parameters of the bone, the patients had double labeling
      with tetracycline. The biopsy is taken in local anesthesia from the anterior iliac spine
      vertically.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Evidence of kidney patients adynamic or hyperdynamic bone disease assessed by 18F-PET-TT
time frame: 3 years
description: 18F-PET correlates with histomorphometric markers in bone biopsy
arm group label: 18F-PET-TT
arm group type: Other
intervention type: Device
intervention name: 18F-PET-TT
description: can 18F-PET-TT be used as an diagnostic tool in patients with CKD-MBD
arm group label: 18F-PET-TT
criteria: 
gender: All
minimum age: 25 Years
maximum age: 95 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kaj Metsärinne, LT
role: Study Director
affiliation: Senior physician /TYKS - nefrologia ja dialyysihoidot
last name: Louise Aaltonen, LL
phone: 023138003
email: louise.aaltonen@tyks.fi
last name: Niina Koivuviita, LT
email: Niina.Koivuviita@tyks.fi
facility: 
status: Recruiting
contact: 
investigator: 
country: Finland
url: https://doi.org/10.1016/j.bone.2020.115267
description: Correlation between 18F-Sodium Fluoride positron emission tomography and bone histomorphometry in dialysis patients
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
sharing ipd: No