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/NCT05998863</url>
    </required_header>
    <id_info>
      <org_study_id>STU-2023-0340</org_study_id>
      <nct_id>NCT05998863</nct_id>
    </id_info>
    <brief_title>Effervescent Calcium Magnesium Citrate to Prevent Mineral Metabolism and Renal Complications of Chronic Proton Pump Inhibitor Therapy</brief_title>
    <official_title>Effervescent Calcium Magnesium Citrate to Prevent Mineral Metabolism and Renal Complications of Chronic Proton Pump Inhibitor Therapy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Texas Southwestern Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Texas Southwestern Medical Center</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Proton pump inhibitors (PPIs) are widely used for the control of gastric ulcer-gastritis,&#xD;
        erosive esophagitis (gastroesophageal reflux disease), peptic ulcer disease (duodenal ulcer),&#xD;
        and heartburn. Despite their efficacy, their use has been implicated in possibly causing&#xD;
        fragility fractures (osteoporosis), hypomagnesemia (magnesium deficiency) and increased risk&#xD;
        of chronic kidney disease (CKD). The current trial represents the investigators ongoing&#xD;
        effort to discern whether these complications could be averted by effervescent calcium&#xD;
        magnesium citrate (EffCaMgCit).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In the current proposal, the investigators wish to conduct a 1-year treatment trial, directed&#xD;
        at obtaining more definitive evidence that EffCaMgCit overcomes all three complications of&#xD;
        PPI.&#xD;
  &#xD;
        Aim 1. To test the hypothesis that EffCaMgCit would prevent/treat osteoporosis, by&#xD;
        suppressing parathyroid function and bone resorption, thereby stabilizing bone mineral&#xD;
        density (BMD). The critical endpoint will be overall change in BMD T-Score and Z-Score from&#xD;
        baseline to the end of study. Secondary endpoints will be the change in serum PTH and&#xD;
        C-terminal telopeptide (CTX).&#xD;
  &#xD;
        Aim 2. To test the hypothesis that EffCaMgCit would prevent/treat hypomagnesemia/magnesium&#xD;
        deficiency, by providing bioavailable magnesium. The critical endpoint will be the overall&#xD;
        change in the fractional excretion of magnesium (FEMg) and free muscle magnesium by MRS from&#xD;
        baseline to the end of study. Secondary endpoints will be the change in serum and urinary&#xD;
        magnesium.&#xD;
  &#xD;
        Aim 3. To test the hypothesis that EffCaMgCit would reduce the risk of CKD during PPI use by&#xD;
        averting putative hypomagnesemia/magnesium deficiency and neutralizing acid load. The&#xD;
        investigators propose that PPI causes hypomagnesemia/magnesium deficiency and confers an acid&#xD;
        load, - factors implicated for incident CKD and its progression. EffCaMgCit is expected to&#xD;
        avert incident CKD by providing bioavailable magnesium and alkali load. Critical endpoints&#xD;
        will be the overall change in endogenous creatinine clearance, urinary alpha-1 microglobulin,&#xD;
        and a measure of acid-base status.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2025</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>To provide adequate blinding, each medication sachet will be labelled with the study name, IRB number, principal investigator's name, expiration date and identification number of the study subject. Labels will be applied to the appropriate medication sachets once the subject has been randomized and assigned to a treatment group. Labelling of the sachets will be done by personnel who are not engaged in patient care.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Change From Baseline in Bone Mineral Density (BMD) T-Score at 1 Year</measure>
      <time_frame>Baseline and 1 year</time_frame>
      <description>Change in Bone Mineral Density (BMD) T-Score from baseline to 1 Year as measured by dual photon absorptiometry. The range, as defined by the World Health Organization (WHO), for T-Score is: -1 and above = Normal, Between -1 and -2.5 = Osteopenia, -2.5 and below = osteoporosis.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 1 Year</measure>
      <time_frame>Baseline and 1 year</time_frame>
      <description>Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 1 Year as measured by the ratio of magnesium clearance and creatinine clearance, using 24-h urinary magnesium and creatinine and corresponding serum magnesium and creatinine obtained post meal/load.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in endogenous creatinine clearance at 1 year.</measure>
      <time_frame>Baseline and 1 year</time_frame>
      <description>Change from baseline in endogenous creatinine clearance at 1 year. Endogenous creatinine clearance will be obtained by using 24-h urinary creatinine and post-meal/load venous blood sample ((uCr, mg/24hr) / (sCr, mg/dL * 14.4)) as well as using the Cockcroft and Gault formula ([(140 - age) x TBW] / (Scr x 72) (x 0.85 for females)).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change From Baseline in Bone Mineral Density (BMD) Z-Score at 1 Year</measure>
      <time_frame>Baseline and 1 year</time_frame>
      <description>Change From Baseline in Bone Mineral Density (BMD) Z-Score at 1 Year as measured by dual photon absorptiometry. Outcome is considered positive if the Z Score after one year of treatment becomes less negative (less than -2). There is no specific score range for the Z Score.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change From Baseline in Free Muscle Magnesium at 1 Year</measure>
      <time_frame>Baseline and 1 year</time_frame>
      <description>Change From baseline in free muscle magnesium at 1 year as assessed by measuring intracellular Mg in a calf muscle, by using 31P (Phosphorous) magnetic resonance spectroscopy (MRS).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in Serum Parathyroid Function (PTH)</measure>
      <time_frame>Baseline and 1 year</time_frame>
      <description>Change from baseline in serum parathyroid function (PTH) at 1 year will be measured by Biomerica Intact-PTH ELISA.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in C-terminal telopeptide (CTX)</measure>
      <time_frame>Baseline and 1 year</time_frame>
      <description>Change from baseline in serum bone resorption marker C-terminal telopeptide (CTX) at 1 year will be measured by lab finding utilizing ELISA CTX-I (CrossLaps).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Serum Magnesium</measure>
      <time_frame>Baseline and 1 year</time_frame>
      <description>Change from baseline in serum magnesium at 1 year will be measured by ion selective electrode.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Urine Magnesium</measure>
      <time_frame>Baseline and 1 year</time_frame>
      <description>Change from baseline in urine magnesium at 1 year measured by atomic absorption.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">56</enrollment>
    <condition>Osteoporosis</condition>
    <condition>Hypomagnesemia</condition>
    <arm_group>
      <arm_group_label>EffCaMgCit</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>38 meq (760 mg) Ca, 20 meq (243 mg) Mg, and 100 meq total citrate per day; designed to be added to 6 oz water for 1-2 minutes, to be dissolved/suspended before swallowing.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Each sachet of Placebo will contain microcrystalline cellulose, but no calcium, magnesium or citrate. Placebo will be added to 6 oz water for 1-2 minutes, to be dissolved/suspended before swallowing.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>EffCaMgCit</intervention_name>
      <description>Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.</description>
      <arm_group_label>EffCaMgCit</arm_group_label>
      <other_name>Effervescent calcium magnesium citrate</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Each sachet of Placebo will contain microcrystalline cellulose, but no calcium, magnesium or citrate.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Ambulatory adult subjects (&gt; 21 years of age) of either gender of any ethnicity&#xD;
  &#xD;
            -  Must have taken PPI (omeprazole or equivalent ≥ 20 mg/day, ≥ three times per week, for&#xD;
               at least 2 months)&#xD;
  &#xD;
            -  Expected to continue at a similar dosage&#xD;
  &#xD;
            -  Stage 1 hypertension (with systolic blood pressure &lt;140 and diastolic &lt;90)&#xD;
  &#xD;
            -  Controlled diabetes mellitus Type II with HbA1C less than 7%&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  End-stage renal failure on dialysis&#xD;
  &#xD;
            -  Hypercalcemia,&#xD;
  &#xD;
            -  Hypophosphatemia (serum P &lt; 2.5 mg/dL)&#xD;
  &#xD;
            -  Hypertension stage 2 or higher&#xD;
  &#xD;
            -  Diabetes Type II with HbA1C ≥ 7%&#xD;
  &#xD;
            -  Treatment with adrenocorticosteroids, diuretics, non-steroidal anti-inflammatory&#xD;
               agents - - Regular dose of magnesium supplements, bisphosphonate, teriparatide,&#xD;
               denosumab or selective estrogen receptor modulators&#xD;
  &#xD;
            -  Required to take calcium&#xD;
  &#xD;
          Inclusion/exclusion of other drugs or conditions will be considered on an individual basis.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>21 Years</minimum_age>
      <maximum_age>99 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Khashayar Sakhaee, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>UTSW</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Khashayar Sakhaee, MD</last_name>
      <phone>214-648-0324</phone>
      <email>Khashayar.Sakhaee@UTSouthwestern.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Miranda King, MPH</last_name>
      <phone>214-648-2117</phone>
      <email>Miranda.King@utsouthwestern.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University of Texas Southwestern Medical Center</name>
        <address>
          <city>Dallas</city>
          <state>Texas</state>
          <zip>75390-9107</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>UT Southwestern Medical Center</name>
        <address>
          <city>Dallas</city>
          <state>Texas</state>
          <zip>75390</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 3, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 10, 2023</last_update_submitted>
    <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
      <investigator_full_name>Khashayar Sakhaee</investigator_full_name>
      <investigator_title>Professor, Internal Medicine</investigator_title>
    </responsible_party>
    <keyword>Bone mineral density</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Osteoporosis</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Magnesium citrate</mesh_term>
    </intervention_browse>
    <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/NCT05998863
  org study id: STU-2023-0340
  nct id: NCT05998863
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  Proton pump inhibitors (PPIs) are widely used for the control of gastric ulcer-gastritis,
        erosive esophagitis (gastroesophageal reflux disease), peptic ulcer disease (duodenal ulcer),
        and heartburn. Despite their efficacy, their use has been implicated in possibly causing
        fragility fractures (osteoporosis), hypomagnesemia (magnesium deficiency) and increased risk
        of chronic kidney disease (CKD). The current trial represents the investigators ongoing
        effort to discern whether these complications could be averted by effervescent calcium
        magnesium citrate (EffCaMgCit).
  In the current proposal, the investigators wish to conduct a 1-year treatment trial, directed
        at obtaining more definitive evidence that EffCaMgCit overcomes all three complications of
        PPI.
  
        Aim 1. To test the hypothesis that EffCaMgCit would prevent/treat osteoporosis, by
        suppressing parathyroid function and bone resorption, thereby stabilizing bone mineral
        density (BMD). The critical endpoint will be overall change in BMD T-Score and Z-Score from
        baseline to the end of study. Secondary endpoints will be the change in serum PTH and
        C-terminal telopeptide (CTX).
  
        Aim 2. To test the hypothesis that EffCaMgCit would prevent/treat hypomagnesemia/magnesium
        deficiency, by providing bioavailable magnesium. The critical endpoint will be the overall
        change in the fractional excretion of magnesium (FEMg) and free muscle magnesium by MRS from
        baseline to the end of study. Secondary endpoints will be the change in serum and urinary
        magnesium.
  
        Aim 3. To test the hypothesis that EffCaMgCit would reduce the risk of CKD during PPI use by
        averting putative hypomagnesemia/magnesium deficiency and neutralizing acid load. The
        investigators propose that PPI causes hypomagnesemia/magnesium deficiency and confers an acid
        load, - factors implicated for incident CKD and its progression. EffCaMgCit is expected to
        avert incident CKD by providing bioavailable magnesium and alkali load. Critical endpoints
        will be the overall change in endogenous creatinine clearance, urinary alpha-1 microglobulin,
        and a measure of acid-base status.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: To provide adequate blinding, each medication sachet will be labelled with the study name, IRB number, principal investigator's name, expiration date and identification number of the study subject. Labels will be applied to the appropriate medication sachets once the subject has been randomized and assigned to a treatment group. Labelling of the sachets will be done by personnel who are not engaged in patient care.
  measure: Change From Baseline in Bone Mineral Density (BMD) T-Score at 1 Year
  time frame: Baseline and 1 year
  description: Change in Bone Mineral Density (BMD) T-Score from baseline to 1 Year as measured by dual photon absorptiometry. The range, as defined by the World Health Organization (WHO), for T-Score is: -1 and above = Normal, Between -1 and -2.5 = Osteopenia, -2.5 and below = osteoporosis.
  measure: Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 1 Year
  time frame: Baseline and 1 year
  description: Change From Baseline in the Fractional Excretion of Magnesium (FEMg) at 1 Year as measured by the ratio of magnesium clearance and creatinine clearance, using 24-h urinary magnesium and creatinine and corresponding serum magnesium and creatinine obtained post meal/load.
  measure: Change from baseline in endogenous creatinine clearance at 1 year.
  time frame: Baseline and 1 year
  description: Change from baseline in endogenous creatinine clearance at 1 year. Endogenous creatinine clearance will be obtained by using 24-h urinary creatinine and post-meal/load venous blood sample ((uCr, mg/24hr) / (sCr, mg/dL * 14.4)) as well as using the Cockcroft and Gault formula ([(140 - age) x TBW] / (Scr x 72) (x 0.85 for females)).
  measure: Change From Baseline in Bone Mineral Density (BMD) Z-Score at 1 Year
  time frame: Baseline and 1 year
  description: Change From Baseline in Bone Mineral Density (BMD) Z-Score at 1 Year as measured by dual photon absorptiometry. Outcome is considered positive if the Z Score after one year of treatment becomes less negative (less than -2). There is no specific score range for the Z Score.
  measure: Change From Baseline in Free Muscle Magnesium at 1 Year
  time frame: Baseline and 1 year
  description: Change From baseline in free muscle magnesium at 1 year as assessed by measuring intracellular Mg in a calf muscle, by using 31P (Phosphorous) magnetic resonance spectroscopy (MRS).
  measure: Change in Serum Parathyroid Function (PTH)
  time frame: Baseline and 1 year
  description: Change from baseline in serum parathyroid function (PTH) at 1 year will be measured by Biomerica Intact-PTH ELISA.
  measure: Change in C-terminal telopeptide (CTX)
  time frame: Baseline and 1 year
  description: Change from baseline in serum bone resorption marker C-terminal telopeptide (CTX) at 1 year will be measured by lab finding utilizing ELISA CTX-I (CrossLaps).
  measure: Change in Serum Magnesium
  time frame: Baseline and 1 year
  description: Change from baseline in serum magnesium at 1 year will be measured by ion selective electrode.
  measure: Change in Urine Magnesium
  time frame: Baseline and 1 year
  description: Change from baseline in urine magnesium at 1 year measured by atomic absorption.
  arm group label: EffCaMgCit
  arm group type: Experimental
  description: 38 meq (760 mg) Ca, 20 meq (243 mg) Mg, and 100 meq total citrate per day; designed to be added to 6 oz water for 1-2 minutes, to be dissolved/suspended before swallowing.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Each sachet of Placebo will contain microcrystalline cellulose, but no calcium, magnesium or citrate. Placebo will be added to 6 oz water for 1-2 minutes, to be dissolved/suspended before swallowing.
  intervention type: Drug
  intervention name: EffCaMgCit
  description: Each sachet of EffCaMgCit will contain 19 meq or 380 mg calcium, 10 meq (122 mg) magnesium, and 50 meq total citrate.
  arm group label: EffCaMgCit
  other name: Effervescent calcium magnesium citrate
  intervention type: Other
  intervention name: Placebo
  description: Each sachet of Placebo will contain microcrystalline cellulose, but no calcium, magnesium or citrate.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 21 Years
  maximum age: 99 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Khashayar Sakhaee, MD
  role: Principal Investigator
  affiliation: UTSW
  last name: Khashayar Sakhaee, MD
  phone: 214-648-0324
  email: Khashayar.Sakhaee@UTSouthwestern.edu
  last name: Miranda King, MPH
  phone: 214-648-2117
  email: Miranda.King@utsouthwestern.edu
  facility: 
  facility: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: University of Texas Southwestern Medical Center
  investigator full name: Khashayar Sakhaee
  investigator title: Professor, Internal Medicine
  mesh term: Osteoporosis
  mesh term: Magnesium citrate
  sharing ipd: No