<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/NCT02225860</url>
  </required_header>
  <id_info>
    <org_study_id>11111</org_study_id>
    <nct_id>NCT02225860</nct_id>
  </id_info>
  <brief_title>Diet as a Potential Treatment for Autosomal Dominant Polycystic Kidney Disease</brief_title>
  <official_title>Low Osmolar Diet and Adjusted Water Intake for Vasopressin Suppression in ADPKD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tufts Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tufts Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to learn if dietary habits can affect vasopressin secretion in&#xD;
      patients with autosomal dominant polycystic kidney disease. Vasopressin increases the growth&#xD;
      of kidney cysts and accelerates disease progression. Understanding how to control secretion&#xD;
      of this hormone based on dietary habits may help to develop treatments to control this&#xD;
      disease. The study will include about 60 patients from Tufts Medical Center. The study will&#xD;
      last for 2 weeks. Blood and urine tests will be done 3 times during the study period.&#xD;
      Subjects will be randomly assigned (by chance like flipping a coin), to one of two study&#xD;
      groups. Group 1 will be given instructions to adjust their diet. This will include adjusting&#xD;
      the amount of water, protein, and salt intake. Group 2 will have no adjustment of diet or&#xD;
      water. The project has tremendous public health relevance, given the large numbers of people&#xD;
      affected by autosomal dominant polycystic kidney disease and the substantial impact of the&#xD;
      disease on morbidity, mortality, hospitalizations,dialysis or transplant, and societal costs&#xD;
      of caring for those patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney&#xD;
      disease with an estimated 600,000 persons affected in the United States and 12.5 million&#xD;
      persons worldwide. To date, no disease-modifying treatment has been approved for the&#xD;
      treatment of ADPKD.&#xD;
&#xD;
      Arginine vasopressin (AVP) is a key player in cyst enlargement and disease progression. It&#xD;
      has been established that patients with ADPKD have higher levels of AVP as compared to&#xD;
      healthy controls. Suppression, blockade or elimination of AVP slows cyst progression. AVP-V2&#xD;
      receptor inhibition controls disease progression in both animal models and humans, as does&#xD;
      genetic elimination of vasopressin in the Polycystic Kidney (PCK) rat. This evidence&#xD;
      indicates that AVP could be a promising target for therapeutic intervention. Unfortunately,&#xD;
      the only clinically tested medication that blocks the AVP-V2 receptor (Tolvaptan) is&#xD;
      associated with side effects including hypernatremia, hyperuricemia and elevated liver&#xD;
      enzymes. An ideal therapeutic approach to target AVP in patients with ADPKD would be safe,&#xD;
      easy to administer and could be adopted early in the disease process to prevent permanent&#xD;
      kidney damage. High fluid intake presents one such possible treatment, and has been shown to&#xD;
      suppress plasma levels of AVP, and slow cyst progression in an animal model of polycystic&#xD;
      kidney disease. However, adherence to a high fluid intake diet is difficult to maintain in&#xD;
      clinical practice.&#xD;
&#xD;
      To address this adherence challenge, The investigators have developed a stepwise approach of&#xD;
      combining a low osmolar diet (low protein and salt) with adjusted water intake, with the goal&#xD;
      of lowering the amount of water intake needed to suppress AVP secretion. The major objective&#xD;
      of this proposal is to evaluate whether this intervention can suppress vasopressin secretion&#xD;
      in patients with early ADPKD. Vasopressin suppression will be assessed by measuring copeptin&#xD;
      levels, which have been shown to be a reliable surrogate marker for the circulating AVP&#xD;
      concentration.&#xD;
&#xD;
      The rationale for this proposal is based on the fact that part of the difficulty in&#xD;
      sustaining a low AVP level with daily water ingestion is the consumption of a diet that&#xD;
      generates a large number of osmoles; high osmolar load stimulates vasopressin secretion to&#xD;
      maintain water homeostasis. Hence, combining a low osmolar diet with adjusted water intake&#xD;
      might prove to be sufficient to suppress vasopressin secretion in the clinical setting. The&#xD;
      investigators propose the following:&#xD;
&#xD;
      Specific Aim: To conduct a randomized controlled trial to evaluate the effect of a low&#xD;
      osmolar diet and high water intake intervention on vasopressin secretion, urine osmolality,&#xD;
      and daily solute excretion in adult patients with ADPKD. The investigators hypothesize that a&#xD;
      low osmolar diet combined with adjusted water intake will decrease serum copeptin level and&#xD;
      total daily solute excretion in patients with ADPKD as compared to the control arm.&#xD;
&#xD;
      To accomplish the research goals, the current proposal builds upon existing expertise at&#xD;
      Tufts Medical Center in conducting controlled clinical trials in patients with ADPKD.&#xD;
&#xD;
      The expected outcomes include the identification of a relevant, safe, easily tolerated and&#xD;
      affordable intervention that can suppress vasopressin secretion in ADPKD patients early in&#xD;
      the disease process; the proposed stepwise approach of combining a low osmolar diet and&#xD;
      adjusted water intake carries the premise of lowering the amount of water needed to suppress&#xD;
      AVP secretion and potentially slow the progression of this devastating disorder.&#xD;
&#xD;
      The study long-term goal is to evaluate whether this therapeutic approach could be tolerated&#xD;
      by patients over a longer period of time, and could impact clinical outcome measures such as&#xD;
      kidney volume and kidney function progression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">February 2016</completion_date>
  <primary_completion_date type="Actual">February 2016</primary_completion_date>
  <phase>Phase 2/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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Mean Serum Copeptin From Baseline (a Reflection of Endogenous Vasopressin Production) at Week 2</measure>
    <time_frame>Baseline to week 2</time_frame>
    <description>The copeptin level will reflect the combined effect of low osmolar diet and adjusted water intake at week 2</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Total Daily Urinary Solutes From Baseline to Week 2</measure>
    <time_frame>Baseline to week 2</time_frame>
    <description>Total daily urinary solutes (this will serve as a surrogate for diet adherence and is known to be associated with lower vasopressin secretion).&#xD;
Total daily solutes is the total amount of osmoles detected in 24 hours urine collection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Mean Serum Copeptin Level From Baseline to Week 1</measure>
    <time_frame>baseline to week 1</time_frame>
    <description>Mean serum copeptin level at week one which will reflect the effect of low osmolar diet alone.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Autosomal Dominant Polycystic Kidney Disease (ADPKD)</condition>
  <arm_group>
    <arm_group_label>Diet and Water adjustment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Reduction in dietary salt and protein intake</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Continue with usual diet</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Diet and water adjustment</intervention_name>
    <description>The dietary intervention consisted of three elements: low sodium (1500 mg/day), low protein (daily protein dietary allowance of 0.8 gram/kg body weight), and low urea (avoidance of preservatives, food additives, bulking agents, and chewing gum). Protein was factored by measured body weight to mirror the estimated average requirement (EAR) of healthy adults which is set on a grams per kilogram basis</description>
    <arm_group_label>Diet and Water adjustment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults 18 to 60 years of age, who have ADPKD with an estimated glomerular filtration&#xD;
             rate (eGFR) of 60 ml/min/1.73m2 or above&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients on chronic use of medications known to affect AVP secretion (Serotonin&#xD;
             Specific Reuptake inhibitors (SSRI), Opioids, Tricyclic Antidepressants (TCA) and&#xD;
             Tolvaptan)&#xD;
&#xD;
          2. History of diseases influencing renal concentration capacity, such as, diabetes&#xD;
             insipidus, adrenal or thyroid deficiencies, present or prior use of lithium, or kidney&#xD;
             diseases other than ADPKD.&#xD;
&#xD;
          3. Baseline hyponatremia (Na below 135 mEq/l)&#xD;
&#xD;
          4. Inability to comply with dietary or fluid requirements&#xD;
&#xD;
          5. Have physical or cognitive impairments which prevent participation&#xD;
&#xD;
          6. Pregnant women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ronald Perrone, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tufts Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Osama Amro, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tufts Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>August 20, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <results_first_submitted>December 2, 2016</results_first_submitted>
  <results_first_submitted_qc>February 10, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">March 30, 2017</results_first_posted>
  <last_update_submitted>February 10, 2017</last_update_submitted>
  <last_update_submitted_qc>February 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ADPKD</keyword>
  <keyword>Copeptin</keyword>
  <keyword>Vasopressin</keyword>
  <keyword>Diet</keyword>
  <keyword>Water</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Polycystic Kidney Diseases</mesh_term>
    <mesh_term>Polycystic Kidney, Autosomal Dominant</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Diet and Water Adjustment</title>
          <description>Reduction in dietary salt and protein intake&#xD;
Diet and water adjustment</description>
        </group>
        <group group_id="P2">
          <title>Control</title>
          <description>Continue with usual diet</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Diet and Water Adjustment</title>
          <description>Reduction in dietary salt and protein intake&#xD;
Diet and water adjustment</description>
        </group>
        <group group_id="B2">
          <title>Control</title>
          <description>Continue with usual diet</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="17"/>
            <count group_id="B2" value="17"/>
            <count group_id="B3" value="34"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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>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="14"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </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="17"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Mean Serum Copeptin From Baseline (a Reflection of Endogenous Vasopressin Production) at Week 2</title>
        <description>The copeptin level will reflect the combined effect of low osmolar diet and adjusted water intake at week 2</description>
        <time_frame>Baseline to week 2</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Diet and Water Adjustment</title>
            <description>Reduction in dietary salt and protein intake&#xD;
Diet and water adjustment</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Continue with usual diet</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean Serum Copeptin From Baseline (a Reflection of Endogenous Vasopressin Production) at Week 2</title>
          <description>The copeptin level will reflect the combined effect of low osmolar diet and adjusted water intake at week 2</description>
          <units>pmole/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.86" spread="1.3"/>
                    <measurement group_id="O2" value="0.39" spread="1.2"/>
                  </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>
            <groups_desc>The analysis of the primary and secondary outcome was based on an intention to treat principle. Copeptin was measured in each subject at baseline and week 2 and the change from baseline to end point (&quot;delta&quot;) was calculated for all subjects. The delta copeptin between subjects in the intervention and control arms was compared with a two sample t test for independent groups. One sample t-tests of the delta were used to examine whether there was any change over time for each group separately.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.01</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Total Daily Urinary Solutes From Baseline to Week 2</title>
        <description>Total daily urinary solutes (this will serve as a surrogate for diet adherence and is known to be associated with lower vasopressin secretion).&#xD;
Total daily solutes is the total amount of osmoles detected in 24 hours urine collection.</description>
        <time_frame>Baseline to week 2</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Diet and Water Adjustment</title>
            <description>Reduction in dietary salt and protein intake&#xD;
Diet and water adjustment</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Continue with usual diet</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total Daily Urinary Solutes From Baseline to Week 2</title>
          <description>Total daily urinary solutes (this will serve as a surrogate for diet adherence and is known to be associated with lower vasopressin secretion).&#xD;
Total daily solutes is the total amount of osmoles detected in 24 hours urine collection.</description>
          <units>mOsm/Day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-120" spread="212"/>
                    <measurement group_id="O2" value="27" spread="79"/>
                  </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>
            <groups_desc>The analysis of the primary and secondary outcome was based on an intention to treat principle. Copeptin was measured in each subject at baseline and week 2 and the change from baseline to end point (&quot;delta&quot;) was calculated for all subjects. The delta copeptin between subjects in the intervention and control arms was compared with a two sample t test for independent groups. One sample t-tests of the delta were used to examine whether there was any change over time for each group separately.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.01</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Mean Serum Copeptin Level From Baseline to Week 1</title>
        <description>Mean serum copeptin level at week one which will reflect the effect of low osmolar diet alone.</description>
        <time_frame>baseline to week 1</time_frame>
        <population>At week 1, there was a nonsignificant (t-test) increase in plasma copeptin to 7.1 ±5.6 in the low osmolar diet group and to 6.1 ±5.5 in the control group. The change in mean plasma copeptin level between baseline and week1 was not statistically significant between groups.</population>
        <group_list>
          <group group_id="O1">
            <title>Diet and Water Adjustment</title>
            <description>Reduction in dietary salt and protein intake&#xD;
Diet and water adjustment: The dietary intervention consisted of three elements: low sodium (1500 mg/day), low protein (daily protein dietary allowance of 0.8 gram/kg body weight), and low urea (avoidance of preservatives, food additives, bulking agents, and chewing gum). Protein was factored by measured body weight to mirror the estimated average requirement (EAR) of healthy adults which is set on a grams per kilogram basis</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Continue with usual diet</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean Serum Copeptin Level From Baseline to Week 1</title>
          <description>Mean serum copeptin level at week one which will reflect the effect of low osmolar diet alone.</description>
          <population>At week 1, there was a nonsignificant (t-test) increase in plasma copeptin to 7.1 ±5.6 in the low osmolar diet group and to 6.1 ±5.5 in the control group. The change in mean plasma copeptin level between baseline and week1 was not statistically significant between groups.</population>
          <units>pmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="1.2"/>
                    <measurement group_id="O2" value="1.4" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Diet and Water Adjustment</title>
          <description>Reduction in dietary salt and protein intake&#xD;
Diet and water adjustment</description>
        </group>
        <group group_id="E2">
          <title>Control</title>
          <description>Continue with usual diet</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </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="17"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
              </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>
    <limitations_and_caveats>Small sample size and short follow up duration.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Ronald D. Perrone</name_or_title>
      <organization>Tufts Medical Center</organization>
      <phone>6176362372</phone>
      <email>rperrone@tuftsmedicalcenter.org</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/NCT02225860
org study id: 11111
nct id: NCT02225860
lead sponsor: 
has dmc: No
The purpose of this study is to learn if dietary habits can affect vasopressin secretion in
      patients with autosomal dominant polycystic kidney disease. Vasopressin increases the growth
      of kidney cysts and accelerates disease progression. Understanding how to control secretion
      of this hormone based on dietary habits may help to develop treatments to control this
      disease. The study will include about 60 patients from Tufts Medical Center. The study will
      last for 2 weeks. Blood and urine tests will be done 3 times during the study period.
      Subjects will be randomly assigned (by chance like flipping a coin), to one of two study
      groups. Group 1 will be given instructions to adjust their diet. This will include adjusting
      the amount of water, protein, and salt intake. Group 2 will have no adjustment of diet or
      water. The project has tremendous public health relevance, given the large numbers of people
      affected by autosomal dominant polycystic kidney disease and the substantial impact of the
      disease on morbidity, mortality, hospitalizations,dialysis or transplant, and societal costs
      of caring for those patients.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney
      disease with an estimated 600,000 persons affected in the United States and 12.5 million
      persons worldwide. To date, no disease-modifying treatment has been approved for the
      treatment of ADPKD.

      Arginine vasopressin (AVP) is a key player in cyst enlargement and disease progression. It
      has been established that patients with ADPKD have higher levels of AVP as compared to
      healthy controls. Suppression, blockade or elimination of AVP slows cyst progression. AVP-V2
      receptor inhibition controls disease progression in both animal models and humans, as does
      genetic elimination of vasopressin in the Polycystic Kidney (PCK) rat. This evidence
      indicates that AVP could be a promising target for therapeutic intervention. Unfortunately,
      the only clinically tested medication that blocks the AVP-V2 receptor (Tolvaptan) is
      associated with side effects including hypernatremia, hyperuricemia and elevated liver
      enzymes. An ideal therapeutic approach to target AVP in patients with ADPKD would be safe,
      easy to administer and could be adopted early in the disease process to prevent permanent
      kidney damage. High fluid intake presents one such possible treatment, and has been shown to
      suppress plasma levels of AVP, and slow cyst progression in an animal model of polycystic
      kidney disease. However, adherence to a high fluid intake diet is difficult to maintain in
      clinical practice.

      To address this adherence challenge, The investigators have developed a stepwise approach of
      combining a low osmolar diet (low protein and salt) with adjusted water intake, with the goal
      of lowering the amount of water intake needed to suppress AVP secretion. The major objective
      of this proposal is to evaluate whether this intervention can suppress vasopressin secretion
      in patients with early ADPKD. Vasopressin suppression will be assessed by measuring copeptin
      levels, which have been shown to be a reliable surrogate marker for the circulating AVP
      concentration.

      The rationale for this proposal is based on the fact that part of the difficulty in
      sustaining a low AVP level with daily water ingestion is the consumption of a diet that
      generates a large number of osmoles; high osmolar load stimulates vasopressin secretion to
      maintain water homeostasis. Hence, combining a low osmolar diet with adjusted water intake
      might prove to be sufficient to suppress vasopressin secretion in the clinical setting. The
      investigators propose the following:

      Specific Aim: To conduct a randomized controlled trial to evaluate the effect of a low
      osmolar diet and high water intake intervention on vasopressin secretion, urine osmolality,
      and daily solute excretion in adult patients with ADPKD. The investigators hypothesize that a
      low osmolar diet combined with adjusted water intake will decrease serum copeptin level and
      total daily solute excretion in patients with ADPKD as compared to the control arm.

      To accomplish the research goals, the current proposal builds upon existing expertise at
      Tufts Medical Center in conducting controlled clinical trials in patients with ADPKD.

      The expected outcomes include the identification of a relevant, safe, easily tolerated and
      affordable intervention that can suppress vasopressin secretion in ADPKD patients early in
      the disease process; the proposed stepwise approach of combining a low osmolar diet and
      adjusted water intake carries the premise of lowering the amount of water needed to suppress
      AVP secretion and potentially slow the progression of this devastating disorder.

      The study long-term goal is to evaluate whether this therapeutic approach could be tolerated
      by patients over a longer period of time, and could impact clinical outcome measures such as
      kidney volume and kidney function progression.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Mean Serum Copeptin From Baseline (a Reflection of Endogenous Vasopressin Production) at Week 2
time frame: Baseline to week 2
description: The copeptin level will reflect the combined effect of low osmolar diet and adjusted water intake at week 2
measure: Change in Total Daily Urinary Solutes From Baseline to Week 2
time frame: Baseline to week 2
description: Total daily urinary solutes (this will serve as a surrogate for diet adherence and is known to be associated with lower vasopressin secretion).
Total daily solutes is the total amount of osmoles detected in 24 hours urine collection.
measure: Change in Mean Serum Copeptin Level From Baseline to Week 1
time frame: baseline to week 1
description: Mean serum copeptin level at week one which will reflect the effect of low osmolar diet alone.
arm group label: Diet and Water adjustment
arm group type: Active Comparator
description: Reduction in dietary salt and protein intake
arm group label: Control
arm group type: No Intervention
description: Continue with usual diet
intervention type: Behavioral
intervention name: Diet and water adjustment
description: The dietary intervention consisted of three elements: low sodium (1500 mg/day), low protein (daily protein dietary allowance of 0.8 gram/kg body weight), and low urea (avoidance of preservatives, food additives, bulking agents, and chewing gum). Protein was factored by measured body weight to mirror the estimated average requirement (EAR) of healthy adults which is set on a grams per kilogram basis
arm group label: Diet and Water adjustment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Ronald Perrone, MD
role: Principal Investigator
affiliation: Tufts Medical Center
last name: Osama Amro, MD
role: Principal Investigator
affiliation: Tufts Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Polycystic Kidney Diseases
mesh term: Polycystic Kidney, Autosomal Dominant
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Small sample size and short follow up duration.
point of contact: 