<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/NCT01696448</url>
  </required_header>
  <id_info>
    <org_study_id>AVR-2012-01</org_study_id>
    <nct_id>NCT01696448</nct_id>
  </id_info>
  <brief_title>The BANGALORE Study; Combination of Berberine, Lipoic Acid, and Picrorhiza</brief_title>
  <acronym>CAR-191</acronym>
  <official_title>Changes in Appetite, Weight, Body Composition, Endothelial Function and Biomarkers in Patients With the Cardiometabolic Syndrome: Comparison of a Combination of Berberine, Lipoic Acid, and Picrorhiza (CAR-191) Versus Placebo (The &quot;BANGALORE&quot; Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Carmel Biosciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Atlanta Vascular Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Carmel Biosciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Though medical treatment has been effective in the treatment of cardiometabolic diseases&#xD;
      (including coronary atherosclerosis and diabetes mellitus), the incidence of these disorders&#xD;
      continues to be high. Many reasons are responsible, but lifestyle changes, including an&#xD;
      increased prevalence of obesity and the metabolic syndrome, are significant for this cause.&#xD;
      Diagnosis and treatment of obese patients with hypertension requires that health care&#xD;
      providers address the issues of hypertension, glucose intolerance, body weight and&#xD;
      dyslipidemia. A sedentary lifestyle and poor cardiorespiratory fitness are not only&#xD;
      associated with the (cardio) metabolic syndrome but could actually be considered features of&#xD;
      the metabolic syndrome. These issues are significant in the health of certain individuals,&#xD;
      who experience greater difficulty in treated BP control, experience increased hypertensive&#xD;
      and diabetic complications, and have higher levels of obesity.&#xD;
&#xD;
      In this study, the investigators will evaluate the efficacy of the nutritional supplements&#xD;
      berberine, alpha-lipoic acid, and picrorhiza (CAR-191) when consumed 30 minutes before meals,&#xD;
      on appetite suppression, body composition and weight control. Additionally, the investigators&#xD;
      will evaluate the effects of this combination of nutraceuticals on the mechanistic effects of&#xD;
      oxidation, inflammation, and vascular function in a high-risk population with the metabolic&#xD;
      syndrome.&#xD;
&#xD;
      Primary Objective To assess the comparative effect of a combination (known as CAR-191) of&#xD;
      berberine (200 mg), alpha-lipoic acid (150 mg), and picrorhiza (100 mg) three times a day,&#xD;
      compared to placebo three times a day, on parameters relate to appetite suppression, weight&#xD;
      control and body composition in a high risk population with the metabolic syndrome.&#xD;
&#xD;
      Secondary Co-objectives&#xD;
&#xD;
      To evaluate the effects of CAR-191 versus placebo on changes in:&#xD;
&#xD;
        -  Endothelial function using noninvasive brachial artery reactivity (BAR) ultrasound&#xD;
&#xD;
        -  Biomarkers including IL-6, HOMA-IR, HbA1C, hsCRP, adiponectin, plasma/urine&#xD;
           isoprostanes, PAI-1, TNFα-II, aldosterone, and glutathione redox ratio&#xD;
&#xD;
        -  Urinary protein excretion&#xD;
&#xD;
        -  Clinical chemistry including plasma glucose, blood urea nitrogen, creatinine, total&#xD;
           bilirubin, uric acid, transaminases (SGOT/AST, SGPT/ALT), alkaline phosphatase,&#xD;
           C-reactive protein, and lipoproteins&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Though medical treatment has been effective in the treatment of cardiometabolic diseases&#xD;
      (including coronary atherosclerosis and diabetes mellitus), the incidence of these disorders&#xD;
      continues to be high. Many reasons are responsible, but lifestyle changes, including an&#xD;
      increased prevalence of obesity and the metabolic syndrome, are significant for this cause.&#xD;
      Recent reported guidelines by the JNC-VII and National Cholesterol Education Panel/ATP-III&#xD;
      suggest that blood pressure reduction is effective in improving the overall quality of life&#xD;
      and may be helpful in the prevention of cardiovascular disease.&#xD;
&#xD;
      Diagnosis and treatment of obese patients with hypertension requires that health care&#xD;
      providers address the issues of hypertension, glucose intolerance, body weight and&#xD;
      dyslipidemia. Strategies to promote therapeutic lifestyle change (TLC), specifically&#xD;
      increased physical activity and reduced dietary intake resulting in weight loss, are not as&#xD;
      well defined. A sedentary lifestyle and poor cardiorespiratory fitness are not only&#xD;
      associated with the (cardio) metabolic syndrome but could actually be considered features of&#xD;
      the metabolic syndrome. These issues are significant in the health of certain individuals,&#xD;
      who experience greater difficulty in treated BP control, experience increased hypertensive&#xD;
      and diabetic complications, and have higher levels of obesity.&#xD;
&#xD;
      In this study, the investigators will evaluate the efficacy of the nutritional supplements&#xD;
      berberine, alpha-lipoic acid, and picrorhiza (CAR-191) when consumed 30 minutes before meals,&#xD;
      on appetite suppression, body composition and weight control. Additionally, the investigators&#xD;
      will evaluate the effects of this combination of nutraceuticals on the mechanistic effects of&#xD;
      oxidation, inflammation, and vascular function in a high-risk population with the metabolic&#xD;
      syndrome.&#xD;
&#xD;
      The investigators will evaluate the initiation of CAR-191 in patients which meet at least 3&#xD;
      of the 5 criteria (ATP-III guidelines) for the cardiometabolic syndrome. The investigators&#xD;
      will determine whether the CAR-191 combination as compared to placebo provides benefit in&#xD;
      appetite suppression, body composition and certain clinical endpoints, including effects on&#xD;
      endothelial function, lipid levels, and glucose control. This study will analyze the effects&#xD;
      of 12 week administration of CAR-191 versus placebo on these parameters in a population of&#xD;
      patients (n=40) with the cardiometabolic syndrome. The study has a parallel design consisting&#xD;
      of 2 weeks of washout and then 12 weeks of treatment to either CAR-191 or placebo. The total&#xD;
      study period is 14 weeks. Patients will be assigned to the CAR-191 or placebo group in a 3:1&#xD;
      ratio so that 30 patients will receive CAR-191 and 10 patients will receive placebo. See&#xD;
      attached study design.&#xD;
&#xD;
      Primary Objective To assess the comparative effect of a combination (known as CAR-191) of&#xD;
      berberine (200 mg), alpha-lipoic acid (150 mg), and picrorhiza (100 mg) three times a day,&#xD;
      compared to placebo three times a day, on parameters relate to appetite suppression, weight&#xD;
      control and body composition in a high risk population with the metabolic syndrome.&#xD;
&#xD;
      Secondary Co-objectives&#xD;
&#xD;
      To evaluate the effects of CAR-191 versus placebo on changes in:&#xD;
&#xD;
        -  Endothelial function using noninvasive brachial artery reactivity (BAR) ultrasound&#xD;
&#xD;
        -  Biomarkers including IL-6, HOMA-IR, HbA1C, hsCRP, adiponectin, plasma/urine&#xD;
           isoprostanes, PAI-1, TNFα-II, aldosterone, and glutathione redox ratio&#xD;
&#xD;
        -  Urinary protein excretion&#xD;
&#xD;
        -  Clinical chemistry including plasma glucose, blood urea nitrogen, creatinine, total&#xD;
           bilirubin, uric acid, transaminases (SGOT/AST, SGPT/ALT), alkaline phosphatase,&#xD;
           C-reactive protein, and lipoproteins&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">April 2013</completion_date>
  <primary_completion_date type="Actual">April 2013</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>appetite suppression</measure>
    <time_frame>12 weeks</time_frame>
    <description>Change in appetite will be measured through food frequency and appetite questionnaires</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Endothelial function using noninvasive brachial artery reactivity (BAR) ultrasound</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight control</measure>
    <time_frame>12 weeks</time_frame>
    <description>Weight will be measured as body weight in lbs and BMI to see if treatment results in weight loss</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Composition</measure>
    <time_frame>12 weeks</time_frame>
    <description>Body composition will be measured as body fat percentage, fat mass, fat-free mass and waist to hip ratio.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Metabolic Syndrome</condition>
  <arm_group>
    <arm_group_label>Experimental Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CAR-191: Berberine 200mg, Alpha-lipoic Acid 150mg, Picrorhiza 100mg each in a separate capsule, to be taken 3 times a day, 30 minutes before breakfast, lunch and dinner. Total 9 capsules per day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>3 placebo capsules, to be taken 3 times a day, 30 minutes before breakfast, lunch and dinner. Total 9 capsules per day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>CAR-191</intervention_name>
    <description>Patients will be randomized to the CAR-191 intervention group in a 3:1, CAR0-191:placebo ratio. There will be 30 patients in the CAR-191 treatment group.</description>
    <arm_group_label>Experimental Group</arm_group_label>
    <other_name>Berberine</other_name>
    <other_name>Alpha-lipoic Acid</other_name>
    <other_name>Picrorhiza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Patients will be randomised in a 3:1 ratio. There will be 10 patients in the placebo group.</description>
    <arm_group_label>Control Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female subjects ≥ 18 years and ≤ 80 years with (cardio)metabolic syndrome as&#xD;
             identified by investigators, OR&#xD;
&#xD;
          -  Male and female subjects ≥ 18 years and ≤ 80 years with (cardio)metabolic syndrome&#xD;
             defined by ATP-III criteria:&#xD;
&#xD;
        Insulin resistance, identified by 1 of the following&#xD;
&#xD;
          -  Type 2 diabetes with HgA1C &lt; 8.0% or on medical therapy&#xD;
&#xD;
          -  Impaired fasting glucose&#xD;
&#xD;
          -  Impaired glucose tolerance&#xD;
&#xD;
          -  Or for those with normal fasting glucose levels (&lt;100 mg/dl), glucose uptake below the&#xD;
             lowest quartile for background population under investigation under hyperinsulinemic,&#xD;
             euglycemic conditions&#xD;
&#xD;
        Plus any 2 of the following:&#xD;
&#xD;
          -  Plasma triglycerides ≥ 150 mg/dl (≥ 1.7 mmol/L)&#xD;
&#xD;
          -  HDL cholesterol &lt;35 mg/dl (&lt;0.9 mmol/L) in men or &lt;39 mg/dl) (1.0 mmol/L) in women&#xD;
&#xD;
          -  BMI &gt;30 kg/m2 and/or waist:hip ratio &gt; 0.9 in men, &gt;0.85 in women&#xD;
&#xD;
          -  Urinary albumin excretion rate ≥ 20 µg/min or albumin:creatinine ratio ≥ 30 mg/g&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  • Females of childbearing potential who are pregnant, lactating or who do not employ&#xD;
             adequate birth control procedures.&#xD;
&#xD;
               -  Presence of any serious disorder including, renal, pulmonary, hepatic,&#xD;
                  gastrointestinal, endocrine/metabolic (with the exception of non-insulin&#xD;
                  dependent type 2 diabetes), hematologic/oncologic, neurologic and psychiatric&#xD;
                  diseases are exclusionary.&#xD;
&#xD;
               -  History of heart failure.&#xD;
&#xD;
               -  Stroke or heart attack within past 6 months.&#xD;
&#xD;
               -  Use of insulin.&#xD;
&#xD;
               -  Non-dominant upper arm circumference greater than 50 cm. (19.5 inches)&#xD;
&#xD;
               -  Currently using any prescription or over-the-counter weight loss products&#xD;
&#xD;
               -  Previous bariatric surgery or other weight reduction procedures&#xD;
&#xD;
               -  Weight loss or gain of greater than 15 pounds in the last 3 months&#xD;
&#xD;
               -  Past or current diagnosis of an eating disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Syed T Rahman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Atlanta Vascular Research Foundation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Atlanta Vascular Research Foundation</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2014</verification_date>
  <study_first_submitted>August 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2012</study_first_posted>
  <last_update_submitted>November 10, 2014</last_update_submitted>
  <last_update_submitted_qc>November 10, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 13, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Appetite Suppression</keyword>
  <keyword>CAR-191</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>Thioctic Acid</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/NCT01696448
org study id: AVR-2012-01
nct id: NCT01696448
lead sponsor: 
collaborator: 
has dmc: No
Though medical treatment has been effective in the treatment of cardiometabolic diseases
      (including coronary atherosclerosis and diabetes mellitus), the incidence of these disorders
      continues to be high. Many reasons are responsible, but lifestyle changes, including an
      increased prevalence of obesity and the metabolic syndrome, are significant for this cause.
      Diagnosis and treatment of obese patients with hypertension requires that health care
      providers address the issues of hypertension, glucose intolerance, body weight and
      dyslipidemia. A sedentary lifestyle and poor cardiorespiratory fitness are not only
      associated with the (cardio) metabolic syndrome but could actually be considered features of
      the metabolic syndrome. These issues are significant in the health of certain individuals,
      who experience greater difficulty in treated BP control, experience increased hypertensive
      and diabetic complications, and have higher levels of obesity.

      In this study, the investigators will evaluate the efficacy of the nutritional supplements
      berberine, alpha-lipoic acid, and picrorhiza (CAR-191) when consumed 30 minutes before meals,
      on appetite suppression, body composition and weight control. Additionally, the investigators
      will evaluate the effects of this combination of nutraceuticals on the mechanistic effects of
      oxidation, inflammation, and vascular function in a high-risk population with the metabolic
      syndrome.

      Primary Objective To assess the comparative effect of a combination (known as CAR-191) of
      berberine (200 mg), alpha-lipoic acid (150 mg), and picrorhiza (100 mg) three times a day,
      compared to placebo three times a day, on parameters relate to appetite suppression, weight
      control and body composition in a high risk population with the metabolic syndrome.

      Secondary Co-objectives

      To evaluate the effects of CAR-191 versus placebo on changes in:

        -  Endothelial function using noninvasive brachial artery reactivity (BAR) ultrasound

        -  Biomarkers including IL-6, HOMA-IR, HbA1C, hsCRP, adiponectin, plasma/urine
           isoprostanes, PAI-1, TNFα-II, aldosterone, and glutathione redox ratio

        -  Urinary protein excretion

        -  Clinical chemistry including plasma glucose, blood urea nitrogen, creatinine, total
           bilirubin, uric acid, transaminases (SGOT/AST, SGPT/ALT), alkaline phosphatase,
           C-reactive protein, and lipoproteins
Though medical treatment has been effective in the treatment of cardiometabolic diseases
      (including coronary atherosclerosis and diabetes mellitus), the incidence of these disorders
      continues to be high. Many reasons are responsible, but lifestyle changes, including an
      increased prevalence of obesity and the metabolic syndrome, are significant for this cause.
      Recent reported guidelines by the JNC-VII and National Cholesterol Education Panel/ATP-III
      suggest that blood pressure reduction is effective in improving the overall quality of life
      and may be helpful in the prevention of cardiovascular disease.

      Diagnosis and treatment of obese patients with hypertension requires that health care
      providers address the issues of hypertension, glucose intolerance, body weight and
      dyslipidemia. Strategies to promote therapeutic lifestyle change (TLC), specifically
      increased physical activity and reduced dietary intake resulting in weight loss, are not as
      well defined. A sedentary lifestyle and poor cardiorespiratory fitness are not only
      associated with the (cardio) metabolic syndrome but could actually be considered features of
      the metabolic syndrome. These issues are significant in the health of certain individuals,
      who experience greater difficulty in treated BP control, experience increased hypertensive
      and diabetic complications, and have higher levels of obesity.

      In this study, the investigators will evaluate the efficacy of the nutritional supplements
      berberine, alpha-lipoic acid, and picrorhiza (CAR-191) when consumed 30 minutes before meals,
      on appetite suppression, body composition and weight control. Additionally, the investigators
      will evaluate the effects of this combination of nutraceuticals on the mechanistic effects of
      oxidation, inflammation, and vascular function in a high-risk population with the metabolic
      syndrome.

      The investigators will evaluate the initiation of CAR-191 in patients which meet at least 3
      of the 5 criteria (ATP-III guidelines) for the cardiometabolic syndrome. The investigators
      will determine whether the CAR-191 combination as compared to placebo provides benefit in
      appetite suppression, body composition and certain clinical endpoints, including effects on
      endothelial function, lipid levels, and glucose control. This study will analyze the effects
      of 12 week administration of CAR-191 versus placebo on these parameters in a population of
      patients (n=40) with the cardiometabolic syndrome. The study has a parallel design consisting
      of 2 weeks of washout and then 12 weeks of treatment to either CAR-191 or placebo. The total
      study period is 14 weeks. Patients will be assigned to the CAR-191 or placebo group in a 3:1
      ratio so that 30 patients will receive CAR-191 and 10 patients will receive placebo. See
      attached study design.

      Primary Objective To assess the comparative effect of a combination (known as CAR-191) of
      berberine (200 mg), alpha-lipoic acid (150 mg), and picrorhiza (100 mg) three times a day,
      compared to placebo three times a day, on parameters relate to appetite suppression, weight
      control and body composition in a high risk population with the metabolic syndrome.

      Secondary Co-objectives

      To evaluate the effects of CAR-191 versus placebo on changes in:

        -  Endothelial function using noninvasive brachial artery reactivity (BAR) ultrasound

        -  Biomarkers including IL-6, HOMA-IR, HbA1C, hsCRP, adiponectin, plasma/urine
           isoprostanes, PAI-1, TNFα-II, aldosterone, and glutathione redox ratio

        -  Urinary protein excretion

        -  Clinical chemistry including plasma glucose, blood urea nitrogen, creatinine, total
           bilirubin, uric acid, transaminases (SGOT/AST, SGPT/ALT), alkaline phosphatase,
           C-reactive protein, and lipoproteins
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: appetite suppression
time frame: 12 weeks
description: Change in appetite will be measured through food frequency and appetite questionnaires
measure: Endothelial function using noninvasive brachial artery reactivity (BAR) ultrasound
time frame: 12 weeks
measure: Weight control
time frame: 12 weeks
description: Weight will be measured as body weight in lbs and BMI to see if treatment results in weight loss
measure: Body Composition
time frame: 12 weeks
description: Body composition will be measured as body fat percentage, fat mass, fat-free mass and waist to hip ratio.
arm group label: Experimental Group
arm group type: Experimental
description: CAR-191: Berberine 200mg, Alpha-lipoic Acid 150mg, Picrorhiza 100mg each in a separate capsule, to be taken 3 times a day, 30 minutes before breakfast, lunch and dinner. Total 9 capsules per day.
arm group label: Control Group
arm group type: Placebo Comparator
description: 3 placebo capsules, to be taken 3 times a day, 30 minutes before breakfast, lunch and dinner. Total 9 capsules per day.
intervention type: Dietary Supplement
intervention name: CAR-191
description: Patients will be randomized to the CAR-191 intervention group in a 3:1, CAR0-191:placebo ratio. There will be 30 patients in the CAR-191 treatment group.
arm group label: Experimental Group
other name: Berberine
other name: Alpha-lipoic Acid
other name: Picrorhiza
intervention type: Other
intervention name: Placebo
description: Patients will be randomised in a 3:1 ratio. There will be 10 patients in the placebo group.
arm group label: Control Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Syed T Rahman, MD
role: Principal Investigator
affiliation: Atlanta Vascular Research Foundation
facility: 
country: United States
responsible party type: Sponsor
mesh term: Metabolic Syndrome
mesh term: Syndrome
mesh term: Thioctic Acid