<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/NCT01664650</url>
  </required_header>
  <id_info>
    <org_study_id>20073XZSR3_003</org_study_id>
    <nct_id>NCT01664650</nct_id>
  </id_info>
  <brief_title>Effects of Genistein in Postmenopausal Women With Metabolic Syndrome</brief_title>
  <official_title>Role of Genistein on Metabolic Syndrome in Post-menopausal Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Messina</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Education, Universities and Research, Italy</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Messina</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The 15-25% of the population of developed countries suffers for metabolic syndrome. It is&#xD;
      associated with a 2-4 fold increase in cardiovascular morbility and mortality and with a 5- 9&#xD;
      fold increase in developing type II diabetes. MS prevalence increases after the onset of&#xD;
      menopause, because of estrogen deficiency. It is still not clear if menopause itself&#xD;
      increases the risk of cardiovascular diseases in al women or only in those that develop MS.&#xD;
      Many MS patients that show slight modification in cardiovascular and metabolic parameters are&#xD;
      not generally pharmacologically treated since diabetes or alteration in the lipid profile are&#xD;
      not evidenced. In this respect it is of importance to develop new therapeutic strategies to&#xD;
      prevent and treat MS. Genistein (4,5,7-trihydroxyisoflavone), shown a potentially preventive&#xD;
      role on the cardiovascular apparatus in post-menopausal women, may be termed as selective ER&#xD;
      modulator (SERM), since it reveals both ER-alpha full agonist and ER-beta partial agonist&#xD;
      activity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators studied whether genistein may represent an efficacious and safe alternative&#xD;
      for reducing vascular risk in postmenopausal women with metabolic syndrome. The clinical&#xD;
      study was a randomized, double-blind, placebo-controlled study involving 150 patients with&#xD;
      metabolic syndrome. After a 4-week stabilization on a standard fat-reduced diet, participants&#xD;
      were randomly assigned to receive either phytoestrogen genistein (54 mg/day) or placebo for 6&#xD;
      months. At baseline and following treatment fasting plasma glucose, insulin, insulin&#xD;
      resistance (HOMA-IR), lipid concentrations, plasma total homocysteine, leptin, adiponectin&#xD;
      and visfatin were measured. Bioimpedentiometric and nutritional analysis, as well as a safety&#xD;
      assessment of the endometrium and vagina were also performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2008</start_date>
  <completion_date type="Actual">January 2011</completion_date>
  <primary_completion_date type="Actual">November 2010</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>homeostasis model assessment for insulin resistance (HOMA-IR)</measure>
    <time_frame>change from baseline at 6 and 12 months</time_frame>
    <description>HOMA-IR was calculated using the following formula: fasting glucose (mg/dl) X fasting insulin (uIU/ml)/22.5.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>body mass index</measure>
    <time_frame>basal, 6 and 12 months</time_frame>
    <description>The body mass index (BMI) is calculated by dividing the weight measured in kilograms by the square of the height measured in metres [i.e. BMI = Weight (kg)/ Height (m)]2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>basal, 6 and 12 months</time_frame>
    <description>Three seated blood pressure measurements were taken on the right arm with a sphygmomanometer after the participant had been resting for at least 5 min. Blood pressure values were based on the average of the second and third measurements.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic variables</measure>
    <time_frame>basal, 6 and 12 months</time_frame>
    <description>Fasting glucose and insulin were measured in serum collected after an overnight fast using routine methods. Total cholesterol, High Density Lipoprotein-Cholesterol (HDL-C), and triglycerides were measured by using a routine enzymatic method, and the Low-Density Lipoprotein Cholesterol (LDL-C) level was calculated by using the Friedewald formula: [Total cholesterol (mg/dL) - High Density Lipoprotein-Cholesterol (HDL-C) (mg/dL) - triglycerides (mg/dL)/5].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory markers</measure>
    <time_frame>basal, 6 and 12 months</time_frame>
    <description>Serum visfatin, adiponectin, and homocysteine were measured by using an immunoenzymatic assay was measured by using an immunoenzymatic assay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>basal, 6 and 12 months</time_frame>
    <description>Participants were asked about symptoms at clinic visits every 6 months. Standard clinical evaluations and laboratory analyses, including hematologic, renal, and liver function tests, were done every 6 months. Endometrial thickness was evaluated by using ultrasonography at baseline, 6 months, and 1 year. The endometrial thickness was measured in the sagittal plane from 1 basal layer to the other. If the endometrial thickness was 8 mm or greater or if uterine bleeding occurred, hysteroscopy and endometrial biopsy were performed. All unfavorable and unintended clinical effects were considered adverse effects and were evaluated for severity, duration, seriousness, and relation to the study drug and outcome.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Metabolic Syndrome</condition>
  <arm_group>
    <arm_group_label>Lifestyle counseling</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo tablets. All participants were counseled on an moderate hypocaloric, Mediterranean-style diet composed of 25% to 30% energy from fat, less than 10% energy from saturated fatty acids, 55% to 60% energy from carbohydrates, and 15% energy from protein, with a cholesterol intake less than 300 mg/d and fiber intake of 35 g/d or greater.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Genistein</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Genistein 54 mg/day in 2 tablets for 12 months. All participants were counseled on an moderate hypocaloric, Mediterranean-style diet composed of 25% to 30% energy from fat, less than 10% energy from saturated fatty acids, 55% to 60% energy from carbohydrates, and 15% energy from protein, with a cholesterol intake less than 300 mg/d and fiber intake of 35 g/d or greater.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Genistein</intervention_name>
    <arm_group_label>Genistein</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Lifestyle counseling</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Post-menopausal satus&#xD;
&#xD;
          -  The presence of three or more of the five following criteria:&#xD;
&#xD;
               1. waist circumference ≥88 cm;&#xD;
&#xD;
               2. Triglycerides ≥150 mg/dl or on drug treatment for elevated triglycerides;&#xD;
&#xD;
               3. high-density-lipoprotein (HDL) cholesterol &lt;50 mg/dl or on drug treatment for&#xD;
                  reduced HDL-C;&#xD;
&#xD;
               4. Fasting glucose ≥100 mg/dl or on drug treatment for elevated glucose;&#xD;
&#xD;
               5. Blood pressure ≥130/85 mmHg or on antihypertensive drug treatment in a subject&#xD;
                  with a history of hypertension.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  clinical or laboratory evidence of confounding systemic diseases (e.g., chronic renal&#xD;
             or hepatic failure, chronic inflammatory diseases)&#xD;
&#xD;
          -  cardiovascular disease (CVD) defined as documented myocardial infarction, ischaemic&#xD;
             heart disease, coronary heart bypass, coronary angioplasty, cerebral thromboembolism,&#xD;
             and peripheral amputations, or by Minnesota codes 1°1-3, 4°1-4, 5°1-3 at a standard&#xD;
             ECG performed in the 12 months preceding the study;&#xD;
&#xD;
          -  coagulopathy;&#xD;
&#xD;
          -  use of oral or transdermal estrogen, progestin, androgens, selective estrogen receptor&#xD;
             modulators, or other steroids;&#xD;
&#xD;
          -  treatment in the preceding six months with polyunsaturated n-3 fatty acids&#xD;
             supplements, non steroidal anti-inflammatory drugs (NSAIDs) or steroids, that would&#xD;
             interfere with evaluation of the study medication;&#xD;
&#xD;
          -  smoking habit of more than 2 cigarettes daily.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>49 Years</minimum_age>
    <maximum_age>67 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francesco Squadrito, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Messina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Magnia Graecia</name>
      <address>
        <city>Catanzaro</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Messina</name>
      <address>
        <city>Messina</city>
        <zip>98123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Palermo</name>
      <address>
        <city>Palermo</city>
        <zip>90129</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 14, 2012</study_first_posted>
  <last_update_submitted>August 9, 2012</last_update_submitted>
  <last_update_submitted_qc>August 9, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 14, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Messina</investigator_affiliation>
    <investigator_full_name>Francesco Squadrito</investigator_full_name>
    <investigator_title>Full Professor of Pharmacology</investigator_title>
  </responsible_party>
  <keyword>menopause</keyword>
  <keyword>pre-diabetes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Genistein</mesh_term>
  </intervention_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/NCT01664650
org study id: 20073XZSR3_003
nct id: NCT01664650
lead sponsor: 
collaborator: 
has dmc: No
The 15-25% of the population of developed countries suffers for metabolic syndrome. It is
      associated with a 2-4 fold increase in cardiovascular morbility and mortality and with a 5- 9
      fold increase in developing type II diabetes. MS prevalence increases after the onset of
      menopause, because of estrogen deficiency. It is still not clear if menopause itself
      increases the risk of cardiovascular diseases in al women or only in those that develop MS.
      Many MS patients that show slight modification in cardiovascular and metabolic parameters are
      not generally pharmacologically treated since diabetes or alteration in the lipid profile are
      not evidenced. In this respect it is of importance to develop new therapeutic strategies to
      prevent and treat MS. Genistein (4,5,7-trihydroxyisoflavone), shown a potentially preventive
      role on the cardiovascular apparatus in post-menopausal women, may be termed as selective ER
      modulator (SERM), since it reveals both ER-alpha full agonist and ER-beta partial agonist
      activity.
The investigators studied whether genistein may represent an efficacious and safe alternative
      for reducing vascular risk in postmenopausal women with metabolic syndrome. The clinical
      study was a randomized, double-blind, placebo-controlled study involving 150 patients with
      metabolic syndrome. After a 4-week stabilization on a standard fat-reduced diet, participants
      were randomly assigned to receive either phytoestrogen genistein (54 mg/day) or placebo for 6
      months. At baseline and following treatment fasting plasma glucose, insulin, insulin
      resistance (HOMA-IR), lipid concentrations, plasma total homocysteine, leptin, adiponectin
      and visfatin were measured. Bioimpedentiometric and nutritional analysis, as well as a safety
      assessment of the endometrium and vagina were also performed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: homeostasis model assessment for insulin resistance (HOMA-IR)
time frame: change from baseline at 6 and 12 months
description: HOMA-IR was calculated using the following formula: fasting glucose (mg/dl) X fasting insulin (uIU/ml)/22.5.
measure: body mass index
time frame: basal, 6 and 12 months
description: The body mass index (BMI) is calculated by dividing the weight measured in kilograms by the square of the height measured in metres [i.e. BMI = Weight (kg)/ Height (m)]2.
measure: Blood pressure
time frame: basal, 6 and 12 months
description: Three seated blood pressure measurements were taken on the right arm with a sphygmomanometer after the participant had been resting for at least 5 min. Blood pressure values were based on the average of the second and third measurements.
measure: Metabolic variables
time frame: basal, 6 and 12 months
description: Fasting glucose and insulin were measured in serum collected after an overnight fast using routine methods. Total cholesterol, High Density Lipoprotein-Cholesterol (HDL-C), and triglycerides were measured by using a routine enzymatic method, and the Low-Density Lipoprotein Cholesterol (LDL-C) level was calculated by using the Friedewald formula: [Total cholesterol (mg/dL) - High Density Lipoprotein-Cholesterol (HDL-C) (mg/dL) - triglycerides (mg/dL)/5].
measure: Inflammatory markers
time frame: basal, 6 and 12 months
description: Serum visfatin, adiponectin, and homocysteine were measured by using an immunoenzymatic assay was measured by using an immunoenzymatic assay.
measure: Adverse events
time frame: basal, 6 and 12 months
description: Participants were asked about symptoms at clinic visits every 6 months. Standard clinical evaluations and laboratory analyses, including hematologic, renal, and liver function tests, were done every 6 months. Endometrial thickness was evaluated by using ultrasonography at baseline, 6 months, and 1 year. The endometrial thickness was measured in the sagittal plane from 1 basal layer to the other. If the endometrial thickness was 8 mm or greater or if uterine bleeding occurred, hysteroscopy and endometrial biopsy were performed. All unfavorable and unintended clinical effects were considered adverse effects and were evaluated for severity, duration, seriousness, and relation to the study drug and outcome.
arm group label: Lifestyle counseling
arm group type: Placebo Comparator
description: Placebo tablets. All participants were counseled on an moderate hypocaloric, Mediterranean-style diet composed of 25% to 30% energy from fat, less than 10% energy from saturated fatty acids, 55% to 60% energy from carbohydrates, and 15% energy from protein, with a cholesterol intake less than 300 mg/d and fiber intake of 35 g/d or greater.
arm group label: Genistein
arm group type: Experimental
description: Genistein 54 mg/day in 2 tablets for 12 months. All participants were counseled on an moderate hypocaloric, Mediterranean-style diet composed of 25% to 30% energy from fat, less than 10% energy from saturated fatty acids, 55% to 60% energy from carbohydrates, and 15% energy from protein, with a cholesterol intake less than 300 mg/d and fiber intake of 35 g/d or greater.
intervention type: Dietary Supplement
intervention name: Genistein
arm group label: Genistein
intervention type: Dietary Supplement
intervention name: Placebo
arm group label: Lifestyle counseling
criteria: 
gender: Female
minimum age: 49 Years
maximum age: 67 Years
healthy volunteers: No
last name: Francesco Squadrito, MD
role: Principal Investigator
affiliation: University of Messina
facility: 
facility: 
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Messina
investigator full name: Francesco Squadrito
investigator title: Full Professor of Pharmacology
mesh term: Metabolic Syndrome
mesh term: Syndrome
mesh term: Genistein