xml: <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/NCT06017011</url>
    </required_header>
    <id_info>
      <org_study_id>C- PRIME Study</org_study_id>
      <nct_id>NCT06017011</nct_id>
    </id_info>
    <brief_title>Clinico-Radiological Characterisation for Remission of Acute Charcot-Neuroarthropathy of Foot.</brief_title>
    <official_title>Clinico-Radiological Characterisation for Remission of Acute Charcot-Neuroarthropathy of Foot</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Postgraduate Institute of Medical Education and Research</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Postgraduate Institute of Medical Education and Research</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Charcot's neuro-arthropathy is a condition which is generally prevalent among the diabetic&#xD;
        patients. Acute charcot's neuro-arthropathy is characterized by signs of inflammation, hot,&#xD;
        red swelling around the involved joint along with a temperature difference of greater than 2&#xD;
        degree centigrade between the two feet. This is often misdiagnosed as cellulitis, sprains or&#xD;
        deep vein thrombosis. The diagnosis of this condition is mainly made clinically and aided by&#xD;
        x-ray of foot, MRI of foot and sometimes by bone scan. The therapy that is accepted&#xD;
        unanimously is putting on a total contact cast. The duration of this therapy depends on the&#xD;
        regular temperature monitoring of both the feet. When the temperature difference between the&#xD;
        two feet comes down to less than 2 degree centigrade, then it is defined as clinical&#xD;
        remission and the offloading of the foot is stopped. There are other modalities that have&#xD;
        been tried for the treatment of acute charcot's neuro-arthropathy with medications like&#xD;
        methyl prednisolone, bisphosphonates and the effects of medical management of acute charcot's&#xD;
        neuro-arthropathy was a mixed one with no definite recommendation regarding use of medical&#xD;
        management in this condition. If the patients are denied these treatment then there is&#xD;
        progression of the disease process and can lead to the development of chronic changes in the&#xD;
        form of fractures, dislocation, gangrene, foot ulcers and ultimately amputation. The end&#xD;
        point of the treatment with total contact cast is taken as the decrease in the temperature&#xD;
        difference of less than 2 degree centigrade between the two feet. This point is regarded as&#xD;
        the point of clinical remission in cases of acute charcot's neuro-arthropathy. But there has&#xD;
        been instances where there have been 12-33% of recurrences when this clinical remission has&#xD;
        been used as a criteria for discontinuation of offloading. With time, there has been&#xD;
        evolution in the imaging of charcot's neuro-arthropathy. There has been advent of MRI and MRS&#xD;
        of the foot for monitoring of acute charcot's neuro-arthropathy remission which is the most&#xD;
        sensitive technique for the recognition of early bony changes in charcot neuro-arthropathy.&#xD;
        PET scan has also been used including bone scan and FDG PET scan, for the evaluation of acute&#xD;
        charcot's neuro-arthropathy remission. Even with these modalities the actual remission&#xD;
        criteria that would decrease the complication of early offloading as done at the time of&#xD;
        clinical remission, is still missing. So here the investigators aim to monitor the process of&#xD;
        remission of acute charcot-neuroarthopathy of foot both clinically as well as radiologically&#xD;
        with the help of MRI of the foot with diffusion weighted and apparent diffusion coefficient&#xD;
        imaging along with a novel PET scan for charcot's neuroarthropathy, that is F18-Fluoride PET&#xD;
        scan which will given a quantitative estimation of the process of remission of acute&#xD;
        charcot-neuroarthropathy in the form of SUV max. Thus this quantitative value can help to&#xD;
        assess the trends of remission in acute charcot neuroarthropathy of foot.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Charcot's neuro-arthropathy is a condition which is generally prevalent among the diabetic&#xD;
        patient. It is a condition which primarily affects the bones and the joints. The presentation&#xD;
        of charcot's neuro-arthropathy can be an acute or a chronic type depending upon the&#xD;
        temperature difference between the two feet i.e. greater than 2 degree centigrade. Acute&#xD;
        charcot's neuro-arthropathy presents with signs of redness, swelling and raised temperature&#xD;
        of the involved area. The condition if not detected in the acute condition leads to chronic&#xD;
        changes in the joints which leads to joint dislocation, fractures and development of&#xD;
        rocker-bottom foot and also can lead to a state where amputation of the affected foot is&#xD;
        needed.Acute charcot's neuro-arthropathy is characterized by signs of inflammation, hot, red&#xD;
        swelling around the involved joint. This is often misdiagnosed as cellulitis, sprains or deep&#xD;
        vein thrombosis. The diagnosis of this condition is mainly made clinically and aided by x-ray&#xD;
        of foot, MRI of foot and sometimes by bone scan. The therapy that is accepted unanimously is&#xD;
        putting on a total contact cast. The duration of this therapy depends on the regular&#xD;
        temperature monitoring of both the feet. When the temperature difference between the two feet&#xD;
        comes down to less than 2 degree centigrade, then it is defined as clinical remission and the&#xD;
        offloading of the foot is stopped. Keeping in mind the effects of RANKL in the pathogenesis&#xD;
        of acute Charcot neuro-arthropathy, Zoledronic acid was used as a treament modality for acute&#xD;
        charcot neuro-arthropathy. But it showed that it was inferior to the application of total&#xD;
        contact cast. There have been trials were methylprednisolone combined with total contact cast&#xD;
        have been used for treatment and the outcome has been compared with the use of zoledronate in&#xD;
        patients on total contact cast. It had shown that zoledronate with total contact cast had an&#xD;
        improvement of bone mineral density and on the other hand there was a decrease with steroids.&#xD;
        Overall the effects of medical management of acute charcot's neuro-arthropathy was a mixed&#xD;
        one with no definite recommendation regarding use of medical management in this condition. So&#xD;
        total contact cast is the gold standard for the management of acute charcot's&#xD;
        neuro-arthropathy. It has led to the healing of ulcers to the range of 75% in cases of acute&#xD;
        charcot's neuro-arthropathy. If the patients are denied these treatment then there is&#xD;
        progression of the disease process and can lead to the development of chronic changes in the&#xD;
        form of fractures, dislocation, gangrene, foot ulcers and ultimately amputation.&#xD;
  &#xD;
        The end point of the treatment with total contact cast is taken as the decrease in the&#xD;
        temperature difference of less than 2 degree centigrade between the two feet. This point is&#xD;
        regarded as the point of clinical remission in cases of acute charcot's neuro-arthropathy.&#xD;
        But there has been instances where there have been 12-33% of recurrences when this clinical&#xD;
        remission has been used as a criteria for discontinuation of offloading.&#xD;
  &#xD;
        There has been advent of MRI and MRS of the foot for monitoring of acute charcot's&#xD;
        neuro-arthropathy remission which is the most sensitive technique for the recognition of&#xD;
        early bony changes in charcot neuro-arthropathy. PET scan has also been used including bone&#xD;
        scan and FDG PET scan, for the evaluation of acute charcot's neuro-arthropathy remission.&#xD;
        These modalities have been evaluated to test the actual remission of acute charcot's&#xD;
        neuro-arthropathy. Even with these modalities the actual remission criteria that would&#xD;
        decrease the complication of early offloading as done at the time of clinical remission, is&#xD;
        still missing.&#xD;
  &#xD;
        There is no quantitative method avaliable to monitor the process of remission of acute&#xD;
        charcot-neuroarthropathy and accurately lable the remission.&#xD;
  &#xD;
        The pathophysiology of acute charcot neuro-arthropathy has two main postulates. One is the&#xD;
        neurovascular theory in which it is thought to have nerve damage and it leads to increased&#xD;
        local vascularity which leads to activation of increased osteoclastic activity with&#xD;
        development of secondary osteopenia, fractures and deformity. The other theory is the more&#xD;
        accepted one and has attracted a lot of recent research around it. This involves the&#xD;
        neurotraumatic theory where due to the presence of neuropathy in these diabetic patients,&#xD;
        they are not able to realise the microtrauma that they sustain. This leads to the development&#xD;
        of a state of inflammation resulting in the raised levels of raised IL6 and TNFalpha. There&#xD;
        is also activation of the RANKL and OPG pathways leading to bone destruction. This highlights&#xD;
        the importance of RANKL in the pathogenesis of acute charcot neuro-arthropathy.&#xD;
  &#xD;
        Earlier bone scan, MR Spectroscopy, FDG PET scan has been used to evaluate quantitatively the&#xD;
        process of remission of acute charcot-neuroarthropathy. Here we try to quantitate the process&#xD;
        of remission of acute charcot neuroarthropathy by using F18- Fluoride PET scan of the foot&#xD;
        along with MRI of the foot with Diffusion weighted and apparent diffusion coefficient imaging&#xD;
        sequences.&#xD;
  &#xD;
        F18- Fluoride PET scan is a modality that is highly sensitive for bone related pathology. It&#xD;
        gets attached to area where there is increased osteoblastic activity. The mechanism of&#xD;
        skeletal uptake of 18F-NaF is based on ion exchange, which is similar to that of 99mTc-MDP.&#xD;
        Bone has a strong architecture and it is due to a crystalline matrix of calcium and phosphate&#xD;
        known as hydroxyapatite, which is composed of many different positive and negative ions. 18F&#xD;
        ions is exchanged with hydroxyl ions (OH-) on the surface of the hydroxyapatite to form&#xD;
        fluoroapatite. The sensitivity of F18 Fluoride PET Scan is also higher than the F18 FDG PET&#xD;
        scan as well as bone scan for bone related pathologies. Pathologically altered osteoblastic&#xD;
        activity is most efficiently taken up by 18F-NaF-PET, which detects incident photons that&#xD;
        results from positron emission of radioactive fluoride ions that have become incorporated&#xD;
        into the hydroxyapatite surface of newly formed bone.&#xD;
  &#xD;
        It has still not been used in monitoring of remission of acute charcot neuro-arthropathy but&#xD;
        as this gives a quantitative value in the form of SUV, so it can be used in the monitoring of&#xD;
        acute charcot neuro-arthropathy remission.&#xD;
  &#xD;
        MRI of the Foot with Diffusion Weighted Imaging (DWI) sequence in the MRI is used to see if&#xD;
        there is any restriction of the brownian motion. It helps to detect conditions where there is&#xD;
        restriction of the brownian motion like infection. DWI sequence also has an advantage in that&#xD;
        it helps to differentiate osteomyelitis from acute charcot-neuro-arthropathy. Apparent&#xD;
        Diffusion Coefficient (ADC) sequence can give a semi-quantitative value by plotting the graph&#xD;
        from the obtained imaging of the foot and thus it may help in the monitoring of remission.&#xD;
  &#xD;
        It has been postulated that RANKL plays a very pivotal role in the process of development of&#xD;
        acute charcot neuro-arthropathy. The increased levels of RANKL leads to the activation of the&#xD;
        osteoclastic activity and there is extensive destruction of the joints seen. RANKL has been&#xD;
        used for studying the process of remission in acute charcot neuro-arthropathy. It has been&#xD;
        studied that during the follow up of two years in the patients of acute charcot&#xD;
        neuro-arthropathy after the application of total contact cast, there was significant decrease&#xD;
        in the levels and it had come down to comparable values with the healthy controls.&#xD;
  &#xD;
        Osteoprotegerin is another biomarker that has attracted attention for research. This is&#xD;
        generally involved in the inhibition of osteoclatstic activity. So in areas where there is&#xD;
        increase in the osteoclastic activity and elevation of the RANKL, there is also similar&#xD;
        elevation of the OPG levels as well as the osteoclastic and the osteoblastic activities which&#xD;
        go hand in hand.&#xD;
  &#xD;
        So here the investigators want to use these quantitative imaging tools and biochemical&#xD;
        markers to assess the trends of remission in acute charcot neuroarthropathy and compare it&#xD;
        with clinical remission.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">October 19, 2022</start_date>
    <completion_date type="Anticipated">December 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Case-Only</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>SUVmax change in F18 Fluoride PET scan</measure>
      <time_frame>From baseline till 6 months post clinical remission</time_frame>
      <description>To assess the quantitative change in SUVmax in F18- Fluoride PET of the foot from diagnosis to 6months post clinical remission and calculate the cutoff/ Delta (change in SUVmax) in comparison to clinical remission in acute charcot neuro-arthropathy.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>ADC values of the MRI Foot with DWI and ADC</measure>
      <time_frame>From baseline to 6 months post clinical remission</time_frame>
      <description>To assess the trends of ADC values of the MRI Foot with DWI and ADC sequences from baseline to 6months post clinical remission in acute charcot-neuroarthropathy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>RANKL and Osteoprotegerin</measure>
      <time_frame>From baseline to 6 months post clinical remission</time_frame>
      <description>To assess the role of biomarkers and imaging in monitoring the remission of acute charcot neuro-arthropathy.</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Acute Charcot Neuroarthropathy</condition>
    <arm_group>
      <arm_group_label>Acute charcot neuroarthropathy or Acute on Chronic charcot neuroarthropathy</arm_group_label>
      <description>Patients diagnosed with Acute charcot neuroarthropathy or Acute on Chronic charcot neuroarthropathy will be put on Total contact cast and followed till clinical remission and then after that till 6 months post clinical remission.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Total conatact cast</intervention_name>
      <description>Total contact cast will be put on the patient at the diagnosis of Acute charcot neuroarthropathy and the patient will be followed till clinical remission and after that till 6months post clinical remission. F18 Fluoride PET scan and MRI of the foot with DWI and ADC sequence to be done at baseline, Clinical remission, 3months post clinical remission and 6months post clinical remission to quantitate the process of remission.</description>
      <arm_group_label>Acute charcot neuroarthropathy or Acute on Chronic charcot neuroarthropathy</arm_group_label>
    </intervention>
    <biospec_retention>Samples Without DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Blood samples for the estimation of free soluble RANKL and Osteoprotegerin levels.&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          All patients with Diabetes diagnosed with acute charcot neuroarthropathy or acute on&#xD;
          chronic charcot neuroarthropathy.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  All patients with Diabetes,&#xD;
  &#xD;
                 1. Diagnosed both clinically as well as radiologically to be having unilateral acute&#xD;
                    charcot neuro-arthropathy.&#xD;
  &#xD;
                 2. Irrespective of age, glycemic status, CKD staging.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          -1) The patients who are contraindicated for MRI like metallic implants, Pace maker in&#xD;
          situ.&#xD;
  &#xD;
          2) Active infected foot ulcers 3) Osteomyelitis 4) Patients on drugs altering bone&#xD;
          metabolism like bisphosphonates, teriparatide, Denosumab in the past 2 months.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Ashu Rastogi, MD, DM</last_name>
      <role>Principal Investigator</role>
      <affiliation>PGIMER, Chandigarh</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Ashu Rastogi, MD,DM</last_name>
      <phone>9781001046</phone>
      <email>rastogi.ashu@pgi.ac.in</email>
    </overall_contact>
    <location>
      <facility>
        <name>PGIMER</name>
        <address>
          <city>Chandigarh</city>
          <zip>160012</zip>
          <country>India</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Ashu Rastogi, MD,DM</last_name>
        <phone>9781001046</phone>
        <email>rastogi.ashu@pgi.ac.in</email>
      </contact>
    </location>
    <location_countries>
      <country>India</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>March 19, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Postgraduate Institute of Medical Education and Research</investigator_affiliation>
      <investigator_full_name>Ashu Rastogi</investigator_full_name>
      <investigator_title>Associate Professor</investigator_title>
    </responsible_party>
    <keyword>Charcot neuroarthropathy</keyword>
    <keyword>F18 Fluoride PET scan</keyword>
    <keyword>MRI of the Foot</keyword>
    <keyword>RANKL</keyword>
    <keyword>Osteoprotegerin</keyword>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06017011
  org study id: C- PRIME Study
  nct id: NCT06017011
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Charcot's neuro-arthropathy is a condition which is generally prevalent among the diabetic
        patients. Acute charcot's neuro-arthropathy is characterized by signs of inflammation, hot,
        red swelling around the involved joint along with a temperature difference of greater than 2
        degree centigrade between the two feet. This is often misdiagnosed as cellulitis, sprains or
        deep vein thrombosis. The diagnosis of this condition is mainly made clinically and aided by
        x-ray of foot, MRI of foot and sometimes by bone scan. The therapy that is accepted
        unanimously is putting on a total contact cast. The duration of this therapy depends on the
        regular temperature monitoring of both the feet. When the temperature difference between the
        two feet comes down to less than 2 degree centigrade, then it is defined as clinical
        remission and the offloading of the foot is stopped. There are other modalities that have
        been tried for the treatment of acute charcot's neuro-arthropathy with medications like
        methyl prednisolone, bisphosphonates and the effects of medical management of acute charcot's
        neuro-arthropathy was a mixed one with no definite recommendation regarding use of medical
        management in this condition. If the patients are denied these treatment then there is
        progression of the disease process and can lead to the development of chronic changes in the
        form of fractures, dislocation, gangrene, foot ulcers and ultimately amputation. The end
        point of the treatment with total contact cast is taken as the decrease in the temperature
        difference of less than 2 degree centigrade between the two feet. This point is regarded as
        the point of clinical remission in cases of acute charcot's neuro-arthropathy. But there has
        been instances where there have been 12-33% of recurrences when this clinical remission has
        been used as a criteria for discontinuation of offloading. With time, there has been
        evolution in the imaging of charcot's neuro-arthropathy. There has been advent of MRI and MRS
        of the foot for monitoring of acute charcot's neuro-arthropathy remission which is the most
        sensitive technique for the recognition of early bony changes in charcot neuro-arthropathy.
        PET scan has also been used including bone scan and FDG PET scan, for the evaluation of acute
        charcot's neuro-arthropathy remission. Even with these modalities the actual remission
        criteria that would decrease the complication of early offloading as done at the time of
        clinical remission, is still missing. So here the investigators aim to monitor the process of
        remission of acute charcot-neuroarthopathy of foot both clinically as well as radiologically
        with the help of MRI of the foot with diffusion weighted and apparent diffusion coefficient
        imaging along with a novel PET scan for charcot's neuroarthropathy, that is F18-Fluoride PET
        scan which will given a quantitative estimation of the process of remission of acute
        charcot-neuroarthropathy in the form of SUV max. Thus this quantitative value can help to
        assess the trends of remission in acute charcot neuroarthropathy of foot.
  Charcot's neuro-arthropathy is a condition which is generally prevalent among the diabetic
        patient. It is a condition which primarily affects the bones and the joints. The presentation
        of charcot's neuro-arthropathy can be an acute or a chronic type depending upon the
        temperature difference between the two feet i.e. greater than 2 degree centigrade. Acute
        charcot's neuro-arthropathy presents with signs of redness, swelling and raised temperature
        of the involved area. The condition if not detected in the acute condition leads to chronic
        changes in the joints which leads to joint dislocation, fractures and development of
        rocker-bottom foot and also can lead to a state where amputation of the affected foot is
        needed.Acute charcot's neuro-arthropathy is characterized by signs of inflammation, hot, red
        swelling around the involved joint. This is often misdiagnosed as cellulitis, sprains or deep
        vein thrombosis. The diagnosis of this condition is mainly made clinically and aided by x-ray
        of foot, MRI of foot and sometimes by bone scan. The therapy that is accepted unanimously is
        putting on a total contact cast. The duration of this therapy depends on the regular
        temperature monitoring of both the feet. When the temperature difference between the two feet
        comes down to less than 2 degree centigrade, then it is defined as clinical remission and the
        offloading of the foot is stopped. Keeping in mind the effects of RANKL in the pathogenesis
        of acute Charcot neuro-arthropathy, Zoledronic acid was used as a treament modality for acute
        charcot neuro-arthropathy. But it showed that it was inferior to the application of total
        contact cast. There have been trials were methylprednisolone combined with total contact cast
        have been used for treatment and the outcome has been compared with the use of zoledronate in
        patients on total contact cast. It had shown that zoledronate with total contact cast had an
        improvement of bone mineral density and on the other hand there was a decrease with steroids.
        Overall the effects of medical management of acute charcot's neuro-arthropathy was a mixed
        one with no definite recommendation regarding use of medical management in this condition. So
        total contact cast is the gold standard for the management of acute charcot's
        neuro-arthropathy. It has led to the healing of ulcers to the range of 75% in cases of acute
        charcot's neuro-arthropathy. If the patients are denied these treatment then there is
        progression of the disease process and can lead to the development of chronic changes in the
        form of fractures, dislocation, gangrene, foot ulcers and ultimately amputation.
  
        The end point of the treatment with total contact cast is taken as the decrease in the
        temperature difference of less than 2 degree centigrade between the two feet. This point is
        regarded as the point of clinical remission in cases of acute charcot's neuro-arthropathy.
        But there has been instances where there have been 12-33% of recurrences when this clinical
        remission has been used as a criteria for discontinuation of offloading.
  
        There has been advent of MRI and MRS of the foot for monitoring of acute charcot's
        neuro-arthropathy remission which is the most sensitive technique for the recognition of
        early bony changes in charcot neuro-arthropathy. PET scan has also been used including bone
        scan and FDG PET scan, for the evaluation of acute charcot's neuro-arthropathy remission.
        These modalities have been evaluated to test the actual remission of acute charcot's
        neuro-arthropathy. Even with these modalities the actual remission criteria that would
        decrease the complication of early offloading as done at the time of clinical remission, is
        still missing.
  
        There is no quantitative method avaliable to monitor the process of remission of acute
        charcot-neuroarthropathy and accurately lable the remission.
  
        The pathophysiology of acute charcot neuro-arthropathy has two main postulates. One is the
        neurovascular theory in which it is thought to have nerve damage and it leads to increased
        local vascularity which leads to activation of increased osteoclastic activity with
        development of secondary osteopenia, fractures and deformity. The other theory is the more
        accepted one and has attracted a lot of recent research around it. This involves the
        neurotraumatic theory where due to the presence of neuropathy in these diabetic patients,
        they are not able to realise the microtrauma that they sustain. This leads to the development
        of a state of inflammation resulting in the raised levels of raised IL6 and TNFalpha. There
        is also activation of the RANKL and OPG pathways leading to bone destruction. This highlights
        the importance of RANKL in the pathogenesis of acute charcot neuro-arthropathy.
  
        Earlier bone scan, MR Spectroscopy, FDG PET scan has been used to evaluate quantitatively the
        process of remission of acute charcot-neuroarthropathy. Here we try to quantitate the process
        of remission of acute charcot neuroarthropathy by using F18- Fluoride PET scan of the foot
        along with MRI of the foot with Diffusion weighted and apparent diffusion coefficient imaging
        sequences.
  
        F18- Fluoride PET scan is a modality that is highly sensitive for bone related pathology. It
        gets attached to area where there is increased osteoblastic activity. The mechanism of
        skeletal uptake of 18F-NaF is based on ion exchange, which is similar to that of 99mTc-MDP.
        Bone has a strong architecture and it is due to a crystalline matrix of calcium and phosphate
        known as hydroxyapatite, which is composed of many different positive and negative ions. 18F
        ions is exchanged with hydroxyl ions (OH-) on the surface of the hydroxyapatite to form
        fluoroapatite. The sensitivity of F18 Fluoride PET Scan is also higher than the F18 FDG PET
        scan as well as bone scan for bone related pathologies. Pathologically altered osteoblastic
        activity is most efficiently taken up by 18F-NaF-PET, which detects incident photons that
        results from positron emission of radioactive fluoride ions that have become incorporated
        into the hydroxyapatite surface of newly formed bone.
  
        It has still not been used in monitoring of remission of acute charcot neuro-arthropathy but
        as this gives a quantitative value in the form of SUV, so it can be used in the monitoring of
        acute charcot neuro-arthropathy remission.
  
        MRI of the Foot with Diffusion Weighted Imaging (DWI) sequence in the MRI is used to see if
        there is any restriction of the brownian motion. It helps to detect conditions where there is
        restriction of the brownian motion like infection. DWI sequence also has an advantage in that
        it helps to differentiate osteomyelitis from acute charcot-neuro-arthropathy. Apparent
        Diffusion Coefficient (ADC) sequence can give a semi-quantitative value by plotting the graph
        from the obtained imaging of the foot and thus it may help in the monitoring of remission.
  
        It has been postulated that RANKL plays a very pivotal role in the process of development of
        acute charcot neuro-arthropathy. The increased levels of RANKL leads to the activation of the
        osteoclastic activity and there is extensive destruction of the joints seen. RANKL has been
        used for studying the process of remission in acute charcot neuro-arthropathy. It has been
        studied that during the follow up of two years in the patients of acute charcot
        neuro-arthropathy after the application of total contact cast, there was significant decrease
        in the levels and it had come down to comparable values with the healthy controls.
  
        Osteoprotegerin is another biomarker that has attracted attention for research. This is
        generally involved in the inhibition of osteoclatstic activity. So in areas where there is
        increase in the osteoclastic activity and elevation of the RANKL, there is also similar
        elevation of the OPG levels as well as the osteoclastic and the osteoblastic activities which
        go hand in hand.
  
        So here the investigators want to use these quantitative imaging tools and biochemical
        markers to assess the trends of remission in acute charcot neuroarthropathy and compare it
        with clinical remission.
  observational model: Case-Only
  time perspective: Prospective
  measure: SUVmax change in F18 Fluoride PET scan
  time frame: From baseline till 6 months post clinical remission
  description: To assess the quantitative change in SUVmax in F18- Fluoride PET of the foot from diagnosis to 6months post clinical remission and calculate the cutoff/ Delta (change in SUVmax) in comparison to clinical remission in acute charcot neuro-arthropathy.
  measure: ADC values of the MRI Foot with DWI and ADC
  time frame: From baseline to 6 months post clinical remission
  description: To assess the trends of ADC values of the MRI Foot with DWI and ADC sequences from baseline to 6months post clinical remission in acute charcot-neuroarthropathy
  measure: RANKL and Osteoprotegerin
  time frame: From baseline to 6 months post clinical remission
  description: To assess the role of biomarkers and imaging in monitoring the remission of acute charcot neuro-arthropathy.
  arm group label: Acute charcot neuroarthropathy or Acute on Chronic charcot neuroarthropathy
  description: Patients diagnosed with Acute charcot neuroarthropathy or Acute on Chronic charcot neuroarthropathy will be put on Total contact cast and followed till clinical remission and then after that till 6 months post clinical remission.
  intervention type: Other
  intervention name: Total conatact cast
  description: Total contact cast will be put on the patient at the diagnosis of Acute charcot neuroarthropathy and the patient will be followed till clinical remission and after that till 6months post clinical remission. F18 Fluoride PET scan and MRI of the foot with DWI and ADC sequence to be done at baseline, Clinical remission, 3months post clinical remission and 6months post clinical remission to quantitate the process of remission.
  arm group label: Acute charcot neuroarthropathy or Acute on Chronic charcot neuroarthropathy
  Blood samples for the estimation of free soluble RANKL and Osteoprotegerin levels.
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: No
  last name: Ashu Rastogi, MD, DM
  role: Principal Investigator
  affiliation: PGIMER, Chandigarh
  last name: Ashu Rastogi, MD,DM
  phone: 9781001046
  email: rastogi.ashu@pgi.ac.in
  facility: 
  status: Recruiting
  contact: 
  country: India
  responsible party type: Principal Investigator
  investigator affiliation: Postgraduate Institute of Medical Education and Research
  investigator full name: Ashu Rastogi
  investigator title: Associate Professor
  sharing ipd: No