The BANGALORE Study; Combination of Berberine, Lipoic Acid, and Picrorhiza
Condition: Metabolic Syndrome
MeSH terms: Metabolic Syndrome; Syndrome
Study type: Interventional

Summary: 
      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
    

Detailed description: 
      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
    

Intervention name(s): CAR-191; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): 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.; Patients will be randomised in a 3:1 ratio. There will be 10 patients in the placebo group.
Other intervention name(s): Berberine; Alpha-lipoic Acid; Picrorhiza
Intervention MeSH terms: Thioctic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Appetite Suppression; CAR-191