<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/NCT02236598</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00056374</org_study_id>
    <nct_id>NCT02236598</nct_id>
  </id_info>
  <brief_title>The Effects of Potassium on Glucose Metabolism in African Americans</brief_title>
  <official_title>The Effects of Potassium on Glucose Metabolism in African Americans</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      African Americans suffer a disproportionately high risk of diabetes compared to other&#xD;
      Americans. Reasons for race disparities in diabetes incidence are not completely understood.&#xD;
      Although a difference in prevalence of obesity does explain a significant portion of the&#xD;
      racial disparity in diabetes risk, it does not explain all of this disparity. Strategies to&#xD;
      control the diabetes epidemic and reduce its racial disparity often overlook preventive&#xD;
      measures. Currently, the most powerful known strategy for preventing diabetes is weight loss&#xD;
      in the overweight/obese. However, because weight loss is often difficult to achieve and&#xD;
      maintain, other opportunities to prevent diabetes should be identified, particularly in&#xD;
      African Americans. Among potential novel opportunities is correction of low or low-normal&#xD;
      potassium levels (hypokalemia). In secondary analyses, we have found low-normal potassium (K)&#xD;
      to be a novel risk factor for diabetes; and we have found that this association between low-K&#xD;
      and diabetes risk may be stronger in African Americans compared to whites. Therefore, a&#xD;
      previously unrecognized alternative or adjunct strategy for preventing diabetes, particularly&#xD;
      in African Americans, may involve correction of low or low-normal K levels (hypokalemia).&#xD;
      Large-scale, adequately-powered, randomized controlled trials are needed to establish the&#xD;
      effectiveness of this approach. However, prior to those trials, the pathophysiology of the&#xD;
      association between low K and poor glucose metabolism must be understood. This pilot clinical&#xD;
      trial will begin to determine the effect of K supplementation on measures of glucose&#xD;
      metabolism in African Americans.&#xD;
&#xD;
      In this pilot clinical trial, 30 African Americans with prediabetes and a low-normal serum K&#xD;
      [&lt;4.0 milliequivalent/Liter (Eq/L)] will be randomized to K-supplements, 20mEq (2-10mEq&#xD;
      tablets) twice daily or a matching placebo capsules twice daily. Prior to randomization,&#xD;
      baseline measures will be taken including measures of glucose metabolism with a 3-hour oral&#xD;
      glucose tolerance test (OGTT), baseline chemistries and a baseline 24-hour urinary potassium&#xD;
      measurement. Patients will take the intervention daily and will undergo repeat testing of all&#xD;
      of these measures at the end of a 3 month period. The primary endpoint will be change in&#xD;
      glucose tolerance, as measured by change in glucose area-under-the-curve (AUC) of a 3-hour&#xD;
      oral glucose tolerance test (OGTT). Secondary endpoints will include changes in fasting,&#xD;
      1-hour, and 2-hour post-challenge glucose levels, as well as measurements of insulin&#xD;
      secretion and insulin sensitivity as measures by the oral glucose minimal model method.(1)&#xD;
      The baseline data from this trial will allow us to quantify abnormalities in glucose&#xD;
      metabolism in African Americans with prediabetes/early diabetes and low-normal serum K. The&#xD;
      post-intervention data will provide estimates of the impact of K-supplements compared to no&#xD;
      supplements on these abnormalities. Data derived from the pilot study will be used in the&#xD;
      design of a larger scale, adequately powered clinical trial. This trial will also help to&#xD;
      assess the feasibility of recruiting this target population.&#xD;
&#xD;
      With this pilot trial, we will begin to determine whether or not K-supplements, an&#xD;
      inexpensive, well-tolerated, and simple intervention, could help to reduce diabetes risk&#xD;
      among African Americans.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">February 29, 2016</completion_date>
  <primary_completion_date type="Actual">February 29, 2016</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Glucose Tolerance as Measured by Area-under-the-curve</measure>
    <time_frame>Baseline to 3 months</time_frame>
    <description>Change in glucose tolerance, as measured by change in glucose area-under-the-curve (Area Under the Curve (AUC) - measured via the trapezoidal method) of 2 hours from the 3-hour Oral Glucose Tolerance Test (OGTT).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL</measure>
    <time_frame>Baseline to 3 months</time_frame>
    <description>Changes in fasting, 1-hour, and 2-hour post-challenge glucose levels in mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Insulin Secretion as Measured by 2-hour Insulin Area-under-the-curve (AUC)</measure>
    <time_frame>Baseline to 3 months</time_frame>
    <description>Changes in Insulin Secretion as measured by 2-hour insulin area-under-the-curve (AUC - measured via the trapezoidal method) of 2 hours from the 3-hour OGTT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Insulin Sensitivity</measure>
    <time_frame>Baseline to 3 months</time_frame>
    <description>Matsuda Insulin Sensitivity Index was calculated as: 10,000 / square root of [fasting glucose x fasting insulin x mean glucose x mean insulin during Oral Glucose Tolerance Test]).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Borderline Hypokalemia</condition>
  <arm_group>
    <arm_group_label>K+ supplementation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>K-supplement- Klor-Con® M10 is an immediately dispersing extended-release oral dosage form of potassium chloride containing 750 mg of microencapsulated potassium chloride, United States Pharmacopeia (USP) equivalent to 10 milliequivalent (mEq) of potassium in a tablet. Participants will be instructed to take two 10 mEq tablets twice daily in a blinded encapsulated form, for 3 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo - An inert powdered placebo will be identically encapsulated as the Klor-Con intervention tablets to maintain blinding. Participants will be instructed to take two tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
Subjects will be instructed to take the pills</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>K+ supplement</intervention_name>
    <arm_group_label>K+ supplementation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        To be eligible for inclusion in the study the following enrollment criteria must be met:&#xD;
&#xD;
          1. Participants must be 30 years of age or older.&#xD;
&#xD;
          2. They must have a diagnosis of prediabetes defined as a hemoglobin A1c between 5.7-6.5%&#xD;
             measured at the initial screening visit.&#xD;
&#xD;
          3. They must have a serum K+ of 3.3-4.0 mEq/L on 2 occasions, within a 18 month period,&#xD;
             including at initial screening visit. If subject is just outside range for inclusion,&#xD;
             PI may offer the subject the option to repeat their screening serum K+ measurement.&#xD;
&#xD;
          4. The participant must be willing and capable of providing written informed consent.&#xD;
&#xD;
          5. The participant must be available for follow-up and must at minimum have telephone&#xD;
             access.&#xD;
&#xD;
          6. Participants must be able to read/understand English.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants must not have any of the following:&#xD;
&#xD;
               1. Participants must not have evidence of chronic kidney disease with an estimated&#xD;
                  Glomerular Filtration Rate (eGFR) &lt; 60ml/min. All patients will be screened for&#xD;
                  eGFR at the enrollment visit.&#xD;
&#xD;
               2. Participants must not have evidence of diabetes mellitus requiring treatment with&#xD;
                  medications prior to screening visit. The cannot have a random or post-challenge&#xD;
                  glucose ≥ 200mg/dl (from prior labs), A1c level ≥ 6.5% (from prior labs), prior&#xD;
                  physician diagnosis, or use of anti-diabetic medications. If participants have&#xD;
                  glucose levels in the diabetic range at screening visit, they will be eligible to&#xD;
                  continue in study as long as glucose levels are not &gt; 200 mg/dl.&#xD;
&#xD;
               3. Participants must not have a history of endoscopy-verified peptic ulcer disease&#xD;
                  with past history of either gastric or duodenal ulcer.&#xD;
&#xD;
               4. Participants must not have evidence of cardiac arrhythmias, unstable angina or&#xD;
                  cardiac event within 6 months, congestive heart failure, or other conditions that&#xD;
                  might impact follow-up, based on the discretion of the principal investigator.&#xD;
&#xD;
               5. Participants must not be pregnant or intend to get pregnant during the study&#xD;
                  period. The study intervention is safe for pregnant women, so serum pregnancy&#xD;
                  screening is not indicated; however, pregnant women are excluded because&#xD;
                  pregnancy affects glucose homeostasis, which will bias primary outcome&#xD;
                  measurement and damage scientific validity of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ranee C Montgomery, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>September 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <results_first_submitted>February 14, 2017</results_first_submitted>
  <results_first_submitted_qc>April 19, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 23, 2017</results_first_posted>
  <last_update_submitted>April 19, 2017</last_update_submitted>
  <last_update_submitted_qc>April 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>borderline hypokalemia</keyword>
  <keyword>glucose tolerance</keyword>
  <keyword>insulin secretion</keyword>
  <keyword>insulin sensitivity</keyword>
  <keyword>fasting glucose</keyword>
  <keyword>African American</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypokalemia</mesh_term>
    <mesh_term>Potassium Deficiency</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>61 participants (17%) expressed interested in the study and signed informed consent. Of these, 29 participants were deemed eligible based on the results of the screening labs</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>K+ Supplementation</title>
          <description>K-supplement- Klor-Con® M10 is an immediately dispersing extended-release oral dosage form of potassium chloride containing 750 mg of microencapsulated potassium chloride, USP equivalent to 10 mEq of potassium in a tablet. Participants will be instructed to take two 10 mEq tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
K+ supplement</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo - An inert powdered placebo will be identically encapsulated as the Klor-Con intervention tablets to maintain blinding. Participants will be instructed to take two tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
Subjects will be instructed to take the pills&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>14 participants started in the placebo arm, but only 12 completed and included in the Baseline characteristics.</population>
      <group_list>
        <group group_id="B1">
          <title>K+ Supplementation</title>
          <description>K-supplement- Klor-Con® M10 is an immediately dispersing extended-release oral dosage form of potassium chloride containing 750 mg of microencapsulated potassium chloride, USP equivalent to 10 mEq of potassium in a tablet. Participants will be instructed to take two 10 mEq tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
K+ supplement</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo - An inert powdered placebo will be identically encapsulated as the Klor-Con intervention tablets to maintain blinding. Participants will be instructed to take two tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
Subjects will be instructed to take the pills&#xD;
Placebo</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="27"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.9" spread="11.0"/>
                    <measurement group_id="B2" value="52.7" spread="8.9"/>
                    <measurement group_id="B3" value="55.0" spread="10.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34.3" spread="5.4"/>
                    <measurement group_id="B2" value="35.1" spread="5.2"/>
                    <measurement group_id="B3" value="34.8" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Glucose Tolerance as Measured by Area-under-the-curve</title>
        <description>Change in glucose tolerance, as measured by change in glucose area-under-the-curve (Area Under the Curve (AUC) - measured via the trapezoidal method) of 2 hours from the 3-hour Oral Glucose Tolerance Test (OGTT).</description>
        <time_frame>Baseline to 3 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>K+ Supplementation</title>
            <description>K-supplement- Klor-Con® M10 is an immediately dispersing extended-release oral dosage form of potassium chloride containing 750 mg of microencapsulated potassium chloride, USP equivalent to 10 mEq of potassium in a tablet. Participants will be instructed to take two 10 mEq tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
K+ supplement</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo - An inert powdered placebo will be identically encapsulated as the Klor-Con intervention tablets to maintain blinding. Participants will be instructed to take two tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
Subjects will be instructed to take the pills&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Glucose Tolerance as Measured by Area-under-the-curve</title>
          <description>Change in glucose tolerance, as measured by change in glucose area-under-the-curve (Area Under the Curve (AUC) - measured via the trapezoidal method) of 2 hours from the 3-hour Oral Glucose Tolerance Test (OGTT).</description>
          <units>AUC - mg*min/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="328" spread="1779"/>
                    <measurement group_id="O2" value="1000" spread="2378"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5582</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL</title>
        <description>Changes in fasting, 1-hour, and 2-hour post-challenge glucose levels in mg/dL</description>
        <time_frame>Baseline to 3 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>K+ Supplementation</title>
            <description>K-supplement- Klor-Con® M10 is an immediately dispersing extended-release oral dosage form of potassium chloride containing 750 mg of microencapsulated potassium chloride, USP equivalent to 10 mEq of potassium in a tablet. Participants will be instructed to take two 10 mEq tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
K+ supplement</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo - An inert powdered placebo will be identically encapsulated as the Klor-Con intervention tablets to maintain blinding. Participants will be instructed to take two tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
Subjects will be instructed to take the pills&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL</title>
          <description>Changes in fasting, 1-hour, and 2-hour post-challenge glucose levels in mg/dL</description>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change in Fasting Glucose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0667" spread="8.3961"/>
                    <measurement group_id="O2" value="6.0833" spread="7.6093"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change in 1-Hour Glucose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.80" spread="31.36"/>
                    <measurement group_id="O2" value="14.17" spread="37.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change in 2-Hour Glucose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.60" spread="25.82"/>
                    <measurement group_id="O2" value="0.75" spread="24.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Change in Fasting Glucose</non_inferiority_desc>
            <p_value>0.0963</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Change in 1-hour Glucose</non_inferiority_desc>
            <p_value>0.6671</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Change in 2-hour Glucose</non_inferiority_desc>
            <p_value>0.7913</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Insulin Secretion as Measured by 2-hour Insulin Area-under-the-curve (AUC)</title>
        <description>Changes in Insulin Secretion as measured by 2-hour insulin area-under-the-curve (AUC - measured via the trapezoidal method) of 2 hours from the 3-hour OGTT.</description>
        <time_frame>Baseline to 3 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>K+ Supplementation</title>
            <description>K-supplement- Klor-Con® M10 is an immediately dispersing extended-release oral dosage form of potassium chloride containing 750 mg of microencapsulated potassium chloride, USP equivalent to 10 mEq of potassium in a tablet. Participants will be instructed to take two 10 mEq tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
K+ supplement</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo - An inert powdered placebo will be identically encapsulated as the Klor-Con intervention tablets to maintain blinding. Participants will be instructed to take two tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
Subjects will be instructed to take the pills&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Insulin Secretion as Measured by 2-hour Insulin Area-under-the-curve (AUC)</title>
          <description>Changes in Insulin Secretion as measured by 2-hour insulin area-under-the-curve (AUC - measured via the trapezoidal method) of 2 hours from the 3-hour OGTT.</description>
          <units>AUC - pg*min/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71,444" spread="213,221"/>
                    <measurement group_id="O2" value="149,327" spread="378,900"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5294</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Insulin Sensitivity</title>
        <description>Matsuda Insulin Sensitivity Index was calculated as: 10,000 / square root of [fasting glucose x fasting insulin x mean glucose x mean insulin during Oral Glucose Tolerance Test]).</description>
        <time_frame>Baseline to 3 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>K+ Supplementation</title>
            <description>K-supplement- Klor-Con® M10 is an immediately dispersing extended-release oral dosage form of potassium chloride containing 750 mg of microencapsulated potassium chloride, USP equivalent to 10 mEq of potassium in a tablet. Participants will be instructed to take two 10 mEq tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
K+ supplement</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo - An inert powdered placebo will be identically encapsulated as the Klor-Con intervention tablets to maintain blinding. Participants will be instructed to take two tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
Subjects will be instructed to take the pills&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Insulin Sensitivity</title>
          <description>Matsuda Insulin Sensitivity Index was calculated as: 10,000 / square root of [fasting glucose x fasting insulin x mean glucose x mean insulin during Oral Glucose Tolerance Test]).</description>
          <units>AUC - unitless,</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="1.49"/>
                    <measurement group_id="O2" value="-0.87" spread="1.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1604</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The reporting period for SAEs is from the day of randomization and receipt of study medication through 12-week end-of-study visit.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>K+ Supplementation</title>
          <description>K-supplement- Klor-Con® M10 is an immediately dispersing extended-release oral dosage form of potassium chloride containing 750 mg of microencapsulated potassium chloride, USP equivalent to 10 mEq of potassium in a tablet. Participants will be instructed to take two 10 mEq tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
K+ supplement</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo - An inert powdered placebo will be identically encapsulated as the Klor-Con intervention tablets to maintain blinding. Participants will be instructed to take two tablets twice daily in a blinded encapsulated form, for 3 months&#xD;
Subjects will be instructed to take the pills&#xD;
Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Vasovagal Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Ranee Chatterjee Montgomery, M.D.</name_or_title>
      <organization>Duke University Health System</organization>
      <email>ranee.chatterjee@duke.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02236598
org study id: Pro00056374
nct id: NCT02236598
lead sponsor: 
has dmc: No
African Americans suffer a disproportionately high risk of diabetes compared to other
      Americans. Reasons for race disparities in diabetes incidence are not completely understood.
      Although a difference in prevalence of obesity does explain a significant portion of the
      racial disparity in diabetes risk, it does not explain all of this disparity. Strategies to
      control the diabetes epidemic and reduce its racial disparity often overlook preventive
      measures. Currently, the most powerful known strategy for preventing diabetes is weight loss
      in the overweight/obese. However, because weight loss is often difficult to achieve and
      maintain, other opportunities to prevent diabetes should be identified, particularly in
      African Americans. Among potential novel opportunities is correction of low or low-normal
      potassium levels (hypokalemia). In secondary analyses, we have found low-normal potassium (K)
      to be a novel risk factor for diabetes; and we have found that this association between low-K
      and diabetes risk may be stronger in African Americans compared to whites. Therefore, a
      previously unrecognized alternative or adjunct strategy for preventing diabetes, particularly
      in African Americans, may involve correction of low or low-normal K levels (hypokalemia).
      Large-scale, adequately-powered, randomized controlled trials are needed to establish the
      effectiveness of this approach. However, prior to those trials, the pathophysiology of the
      association between low K and poor glucose metabolism must be understood. This pilot clinical
      trial will begin to determine the effect of K supplementation on measures of glucose
      metabolism in African Americans.

      In this pilot clinical trial, 30 African Americans with prediabetes and a low-normal serum K
      [<4.0 milliequivalent/Liter (Eq/L)] will be randomized to K-supplements, 20mEq (2-10mEq
      tablets) twice daily or a matching placebo capsules twice daily. Prior to randomization,
      baseline measures will be taken including measures of glucose metabolism with a 3-hour oral
      glucose tolerance test (OGTT), baseline chemistries and a baseline 24-hour urinary potassium
      measurement. Patients will take the intervention daily and will undergo repeat testing of all
      of these measures at the end of a 3 month period. The primary endpoint will be change in
      glucose tolerance, as measured by change in glucose area-under-the-curve (AUC) of a 3-hour
      oral glucose tolerance test (OGTT). Secondary endpoints will include changes in fasting,
      1-hour, and 2-hour post-challenge glucose levels, as well as measurements of insulin
      secretion and insulin sensitivity as measures by the oral glucose minimal model method.(1)
      The baseline data from this trial will allow us to quantify abnormalities in glucose
      metabolism in African Americans with prediabetes/early diabetes and low-normal serum K. The
      post-intervention data will provide estimates of the impact of K-supplements compared to no
      supplements on these abnormalities. Data derived from the pilot study will be used in the
      design of a larger scale, adequately powered clinical trial. This trial will also help to
      assess the feasibility of recruiting this target population.

      With this pilot trial, we will begin to determine whether or not K-supplements, an
      inexpensive, well-tolerated, and simple intervention, could help to reduce diabetes risk
      among African Americans.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in Glucose Tolerance as Measured by Area-under-the-curve
time frame: Baseline to 3 months
description: Change in glucose tolerance, as measured by change in glucose area-under-the-curve (Area Under the Curve (AUC) - measured via the trapezoidal method) of 2 hours from the 3-hour Oral Glucose Tolerance Test (OGTT).
measure: Changes in Fasting, 1-hour, and 2-hour Post-challenge Glucose Levels in mg/dL
time frame: Baseline to 3 months
description: Changes in fasting, 1-hour, and 2-hour post-challenge glucose levels in mg/dL
measure: Changes in Insulin Secretion as Measured by 2-hour Insulin Area-under-the-curve (AUC)
time frame: Baseline to 3 months
description: Changes in Insulin Secretion as measured by 2-hour insulin area-under-the-curve (AUC - measured via the trapezoidal method) of 2 hours from the 3-hour OGTT.
measure: Changes in Insulin Sensitivity
time frame: Baseline to 3 months
description: Matsuda Insulin Sensitivity Index was calculated as: 10,000 / square root of [fasting glucose x fasting insulin x mean glucose x mean insulin during Oral Glucose Tolerance Test]).
arm group label: K+ supplementation
arm group type: Experimental
description: K-supplement- Klor-Con® M10 is an immediately dispersing extended-release oral dosage form of potassium chloride containing 750 mg of microencapsulated potassium chloride, United States Pharmacopeia (USP) equivalent to 10 milliequivalent (mEq) of potassium in a tablet. Participants will be instructed to take two 10 mEq tablets twice daily in a blinded encapsulated form, for 3 months
arm group label: Placebo
arm group type: Experimental
description: Placebo - An inert powdered placebo will be identically encapsulated as the Klor-Con intervention tablets to maintain blinding. Participants will be instructed to take two tablets twice daily in a blinded encapsulated form, for 3 months
Subjects will be instructed to take the pills
intervention type: Drug
intervention name: K+ supplement
arm group label: K+ supplementation
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: No
last name: Ranee C Montgomery, MD
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hypokalemia
mesh term: Potassium Deficiency
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 