<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/NCT04485793</url>
  </required_header>
  <id_info>
    <org_study_id>NUT1-BO-2019</org_study_id>
    <nct_id>NCT04485793</nct_id>
  </id_info>
  <brief_title>Effect of a Dietary Supplement on Lipid Pattern and Liver Parameters in Hypercholesterolemia</brief_title>
  <official_title>Evaluation of the Effect of a Dietary Supplement on Lipid Pattern and Liver Parameters in Moderately Hypercholesterolemic Subjects: a Double-blind, Placebo-controlled, Randomized, Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Bologna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Bologna</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The joint ESC/EAS guidelines for the management of dyslipidaemias recommend, for patients at&#xD;
      low/moderate CV risk with raised LDL-C, a set of measures collectively defined as &quot;lifestyle&#xD;
      interventions&quot;, with use of drugs only if the LDL-C levels cannot be controlled with such&#xD;
      lifestyle interventions. &quot;Lifestyle interventions&quot; also includes food supplements. The reason&#xD;
      is the following: a simple &quot;dietary advice&quot; has been shown (Cochrane review and&#xD;
      meta-analysis, Rees et al, 2013) to achieve a modest reduction of total-C and LDL-C. The&#xD;
      review reports: Dietary advice reduced total serum cholesterol by 0.15 mmol/L (95% CI 0.06 to&#xD;
      0.23) and LDL cholesterol by 0.16 mmol/L (95% CI 0.08 to 0.24) after 3 to 24 months.&quot; An&#xD;
      average reduction of LDL-C by 0.16 mmol/L (6.2 mg/dL) is definitely insufficient to control&#xD;
      the level of LDL-C in those subjects. Therefore, those subjects would lose motivation to keep&#xD;
      dieting. In this context, use of supplements would significantly amplify the result of diet.&#xD;
&#xD;
      A significant proportion of ischemic cardiovascular events are believed to be supported by&#xD;
      the coexistence of traditional cardiovascular risk factors such as diabetes, hypertension,&#xD;
      dyslipidemia, smoking, and others. The aggregation of these factors is accompanied by a&#xD;
      significant increase in the risk of cardiovascular events.&#xD;
&#xD;
      Observational studies shown the existence of a relationship between cholesterolemia and&#xD;
      coronary heart disease, clearly showing that subjects with even modestly increased total&#xD;
      cholesterol values over time develop both fatal and non-fatal vascular events with a higher&#xD;
      frequency compared to subjects with similar characteristics, but with lower basal values of&#xD;
      cholesterol.&#xD;
&#xD;
      Numerous controlled intervention studies, on the other hand, have shown that there is a close&#xD;
      correlation between cholesterol reduction and cardiovascular risk; in fact, reductions in the&#xD;
      plasma concentration of total and LDL-C, obtained through lifestyle modification or specific&#xD;
      drugs, result in reductions in the incidence of major coronary events. The effectiveness of&#xD;
      these interventions has been demonstrated both in subjects in primary prevention and in&#xD;
      patients in secondary prevention.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 21, 2020</start_date>
  <completion_date type="Actual">October 4, 2021</completion_date>
  <primary_completion_date type="Actual">October 4, 2021</primary_completion_date>
  <phase>N/A</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>LDL-cholesterolemia absolute reduction from baseline and between groups</measure>
    <time_frame>12 weeks</time_frame>
    <description>Absolute reduction of LDL-cholesterolemia after 12 weeks of treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>LDL-cholesterolemia % reduction from baseline and between groups</measure>
    <time_frame>12 weeks</time_frame>
    <description>% reduction of LDL-cholesterolemia after 12 weeks of treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Absolute reduction from baseline and between groups in other lipid fractions, apolipoproteins and their ratios</measure>
    <time_frame>12 weeks</time_frame>
    <description>Absolute reduction of serum concentrations of total cholesterol, HDL-cholesterol, apolipoprotein B, triglycerides and their ratios after 12 weeks of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>% reduction from baseline and between groups in other lipid fractions, apolipoproteins and their ratios</measure>
    <time_frame>12 weeks</time_frame>
    <description>% reduction of of serum concentrations of total cholesterol, HDL-cholesterol, apolipoprotein B, triglycerides and their ratios after 12 weeks of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>% reduction from baseline and between groups in anthropometric parameters</measure>
    <time_frame>12 weeks</time_frame>
    <description>% reduction of body mass index after 12 weeks of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>% reduction from baseline and between groups in blood pressure levels</measure>
    <time_frame>12 weeks</time_frame>
    <description>% reduction of systolic and diastolic blood pressure after 12 weeks of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute reduction from baseline and between groups in blood pressure levels</measure>
    <time_frame>12 weeks</time_frame>
    <description>Absolute reduction of systolic and diastolic blood pressure after 12 weeks of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute reduction from baseline and between groups in anthropometric parameters</measure>
    <time_frame>12 weeks</time_frame>
    <description>Absolute reduction of body mass index after 12 weeks of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>% reduction from baseline and between groups in creatine phosphokinase (CPK) serum levels</measure>
    <time_frame>12 weeks</time_frame>
    <description>% reduction of creatine phosphokinase (CPK) serum levels after 12 weeks of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute reduction from baseline and between groups in creatine phosphokinase (CPK) serum levels</measure>
    <time_frame>12 weeks</time_frame>
    <description>Absolute reduction of creatine phosphokinase (CPK) serum levels after 12 weeks of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute reduction from baseline and between groups in liver parameters</measure>
    <time_frame>12 weeks</time_frame>
    <description>Absolute reduction of GOT, GPT and gamma-GT after 12 weeks of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>% reduction from baseline and between groups in liver parameters</measure>
    <time_frame>12 weeks</time_frame>
    <description>% reduction of GOT, GPT and gamma-GT after 12 weeks of treatment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Hypercholesterolemia</condition>
  <arm_group>
    <arm_group_label>Active Comparator</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dietary supplement</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo comparator</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Dietary supplement</intervention_name>
    <description>Dietary supplement formulated with 400 mg Bergamot d.e. obtained from different parts of the Citrus Bergamot whole fruit (Citrus bergamia Risso et Poiteau, fructus), specifically from fresh fruits collected from November to February (Brumex TM).&#xD;
Oral administration: 1 tablet/day at evening meal</description>
    <arm_group_label>Active Comparator</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral administration: 1 tablet/day at evening meal</description>
    <arm_group_label>Placebo comparator</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects agree to participate in the study and having dated and signed the informed&#xD;
             consent form.&#xD;
&#xD;
          -  Subjects who have the capability to communicate, to make themselves understood, and to&#xD;
             comply with the study's requirements.&#xD;
&#xD;
          -  Male or female aged ≥ 18 years and ≤ 70 years old.&#xD;
&#xD;
          -  LDL-Cholesterol plasma levels &gt;115 mg/dL and &lt; 190 mg/dL.&#xD;
&#xD;
          -  TG&lt;400 mg/dL.&#xD;
&#xD;
          -  Subjects who, according to the SCORE charts, have a low or moderate cardiovascular&#xD;
             risk (defined as a total cardiovascular risk &lt; 5%) and for whom, according to ESC/EAS&#xD;
             guidelines 2012, the intervention strategy does not require a pharmacological&#xD;
             lipid-lowering intervention.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects already affected by cardiovascular diseases (secondary prevention) or with&#xD;
             estimated 10 years cardiovascular disease risk&gt; 5%;&#xD;
&#xD;
          -  Obesity (BMI&gt;30 kg/m2) or diabetes mellitus;&#xD;
&#xD;
          -  Assumption of lipid lowering drugs or food supplements, or drugs potentially affecting&#xD;
             the lipid metabolism;&#xD;
&#xD;
          -  Antihypertensive treatment not stabilized since at least 3 months;&#xD;
&#xD;
          -  Anticoagulants therapy&#xD;
&#xD;
          -  Uncontrolled hypertension (systolic blood pressure&gt; 190 mmHg or diastolic arterial&#xD;
             pressure&gt; 100 mmHg);&#xD;
&#xD;
          -  Known current thyroid, gastrointestinal or hepatobiliary diseases;&#xD;
&#xD;
          -  Any medical or surgical condition that would limit the patient adhesion to the study&#xD;
             protocol;&#xD;
&#xD;
          -  Abuse of alcohol or drugs (current or previous);&#xD;
&#xD;
          -  History of malignant neoplasia in the 5 years prior to enrolment in the study;&#xD;
&#xD;
          -  History or clinical evidence of inflammatory disease such as severe arthritis,&#xD;
             systemic lupus erythematosus or chronic inflammatory diseases or current therapy with&#xD;
             immunosuppressive agents or long-term glucocorticoids;&#xD;
&#xD;
          -  History or clinical evidence of any significant concomitant disease that could&#xD;
             compromise the safety of the subject or the possibility of completing the study;&#xD;
&#xD;
          -  Known previous intolerance to the tested nutraceutical&#xD;
&#xD;
          -  Women in fertile age not using consolidated contraceptive methods&#xD;
&#xD;
          -  Pregnancy and Breastfeeding.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Claudio Borghi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>S. Orsola-Malpighi University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Bologna</name>
      <address>
        <city>Bologna</city>
        <state>BO</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>June 18, 2023</last_update_submitted>
  <last_update_submitted_qc>June 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Bologna</investigator_affiliation>
    <investigator_full_name>Claudio Borghi</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypercholesterolemia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04485793
org study id: NUT1-BO-2019
nct id: NCT04485793
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The joint ESC/EAS guidelines for the management of dyslipidaemias recommend, for patients at
      low/moderate CV risk with raised LDL-C, a set of measures collectively defined as "lifestyle
      interventions", with use of drugs only if the LDL-C levels cannot be controlled with such
      lifestyle interventions. "Lifestyle interventions" also includes food supplements. The reason
      is the following: a simple "dietary advice" has been shown (Cochrane review and
      meta-analysis, Rees et al, 2013) to achieve a modest reduction of total-C and LDL-C. The
      review reports: Dietary advice reduced total serum cholesterol by 0.15 mmol/L (95% CI 0.06 to
      0.23) and LDL cholesterol by 0.16 mmol/L (95% CI 0.08 to 0.24) after 3 to 24 months." An
      average reduction of LDL-C by 0.16 mmol/L (6.2 mg/dL) is definitely insufficient to control
      the level of LDL-C in those subjects. Therefore, those subjects would lose motivation to keep
      dieting. In this context, use of supplements would significantly amplify the result of diet.

      A significant proportion of ischemic cardiovascular events are believed to be supported by
      the coexistence of traditional cardiovascular risk factors such as diabetes, hypertension,
      dyslipidemia, smoking, and others. The aggregation of these factors is accompanied by a
      significant increase in the risk of cardiovascular events.

      Observational studies shown the existence of a relationship between cholesterolemia and
      coronary heart disease, clearly showing that subjects with even modestly increased total
      cholesterol values over time develop both fatal and non-fatal vascular events with a higher
      frequency compared to subjects with similar characteristics, but with lower basal values of
      cholesterol.

      Numerous controlled intervention studies, on the other hand, have shown that there is a close
      correlation between cholesterol reduction and cardiovascular risk; in fact, reductions in the
      plasma concentration of total and LDL-C, obtained through lifestyle modification or specific
      drugs, result in reductions in the incidence of major coronary events. The effectiveness of
      these interventions has been demonstrated both in subjects in primary prevention and in
      patients in secondary prevention.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: LDL-cholesterolemia absolute reduction from baseline and between groups
time frame: 12 weeks
description: Absolute reduction of LDL-cholesterolemia after 12 weeks of treatment
measure: LDL-cholesterolemia % reduction from baseline and between groups
time frame: 12 weeks
description: % reduction of LDL-cholesterolemia after 12 weeks of treatment
measure: Absolute reduction from baseline and between groups in other lipid fractions, apolipoproteins and their ratios
time frame: 12 weeks
description: Absolute reduction of serum concentrations of total cholesterol, HDL-cholesterol, apolipoprotein B, triglycerides and their ratios after 12 weeks of treatment
measure: % reduction from baseline and between groups in other lipid fractions, apolipoproteins and their ratios
time frame: 12 weeks
description: % reduction of of serum concentrations of total cholesterol, HDL-cholesterol, apolipoprotein B, triglycerides and their ratios after 12 weeks of treatment
measure: % reduction from baseline and between groups in anthropometric parameters
time frame: 12 weeks
description: % reduction of body mass index after 12 weeks of treatment
measure: % reduction from baseline and between groups in blood pressure levels
time frame: 12 weeks
description: % reduction of systolic and diastolic blood pressure after 12 weeks of treatment
measure: Absolute reduction from baseline and between groups in blood pressure levels
time frame: 12 weeks
description: Absolute reduction of systolic and diastolic blood pressure after 12 weeks of treatment
measure: Absolute reduction from baseline and between groups in anthropometric parameters
time frame: 12 weeks
description: Absolute reduction of body mass index after 12 weeks of treatment
measure: % reduction from baseline and between groups in creatine phosphokinase (CPK) serum levels
time frame: 12 weeks
description: % reduction of creatine phosphokinase (CPK) serum levels after 12 weeks of treatment
measure: Absolute reduction from baseline and between groups in creatine phosphokinase (CPK) serum levels
time frame: 12 weeks
description: Absolute reduction of creatine phosphokinase (CPK) serum levels after 12 weeks of treatment
measure: Absolute reduction from baseline and between groups in liver parameters
time frame: 12 weeks
description: Absolute reduction of GOT, GPT and gamma-GT after 12 weeks of treatment
measure: % reduction from baseline and between groups in liver parameters
time frame: 12 weeks
description: % reduction of GOT, GPT and gamma-GT after 12 weeks of treatment
arm group label: Active Comparator
arm group type: Active Comparator
description: Dietary supplement
arm group label: Placebo comparator
arm group type: Placebo Comparator
description: Placebo
intervention type: Dietary Supplement
intervention name: Dietary supplement
description: Dietary supplement formulated with 400 mg Bergamot d.e. obtained from different parts of the Citrus Bergamot whole fruit (Citrus bergamia Risso et Poiteau, fructus), specifically from fresh fruits collected from November to February (Brumex TM).
Oral administration: 1 tablet/day at evening meal
arm group label: Active Comparator
intervention type: Other
intervention name: Placebo
description: Oral administration: 1 tablet/day at evening meal
arm group label: Placebo comparator
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Claudio Borghi, MD
role: Principal Investigator
affiliation: S. Orsola-Malpighi University Hospital
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Bologna
investigator full name: Claudio Borghi
investigator title: Professor
mesh term: Hypercholesterolemia