Green Tea Extract for Obesity of Psychiatric Patients
Condition: Obesity; Metabolic Syndrome
MeSH terms: Obesity; Metabolic Syndrome
Study type: Interventional

Summary: 
      Obesity or metabolic syndrome is becoming a global epidemic and common health problem,
      leading to the increase of associated comorbidities such as type 2 diabetes, cardiovascular
      disease, and certain cancers. This phenomenon is also a serious problem among psychiatric
      patients due to the increase use of second generation antipsychotics and mood stabilizers
      such as lithium or valproic acid. These metabolic abnormalities can be regarded as medical
      comorbidities, and have an impact not only on physical health and increased hospital length
      of stay, but also on a lower functional outcome, low self-esteem and poorer quality of life
      and non-compliance to antipsychotics. Green tea is one of the most popular beverages in the
      world and is believed to have beneficial effects in prevention and treatment of many
      diseases, such as cancer-prevention, adjunct to chemotherapy for malignancy, to reduce mental
      and physical stress and improve memory function, to increase bone mineral density, and to
      decrease body weight. Since weight gain is a common and undesirable side effect with
      psychiatric medications, the management of it becomes an important issue in clinical
      practice. In this clinical trial, we will use decaffeinated green tea extract to treat
      overweight patients with schizophrenia or bipolar disorder in a double-blind,
      placebo-controlled study design.
    

Detailed description: 
      Prevalence of obesity or metabolic syndrome and diabetes:

      Obesity or metabolic syndrome is becoming a global epidemic and common health problem. The
      rising prevalence of obesity and associated comorbidities such as type 2 diabetes,
      cardiovascular disease, and certain cancers represents a major threat to public health
      worldwide. In a recent study in Asian populations, the result showed a strong association
      between BMI and prevalence of diabetes. From the results of a general population survey in
      Taiwan, the overall prevalence of obesity (body mass index (BMI) ≧ 27 kg/m2) in men and women
      was 19.2% and 13.4%, respectively, while the age-standardized prevalence of MS was 15.7% by
      the modified Adult Treatment Panel III criteria, 14.3% by the International Diabetes
      Federation for Chinese criteria and 16.4% by the metabolic syndrome criteria for Taiwanese.
      Their data also showed that the prevalence of obesity and metabolic syndrome significantly
      increased with age (trend test, p < 0.0001) in men and women. The risk of metabolic syndrome
      and its components increased significantly with BMI, and showed a marked increase with BMI≧24
      kg/m2.

      Prevalence of obesity or metabolic syndrome and diabetes in psychiatric patients:

      The prevalence of MS among patients with schizophrenia or other psychotic disorder has been
      reported to be high, ranging from 24% to 43% in males and from 27% to 52% in females in
      previous large-scale investigations. These metabolic abnormalities can be regarded as medical
      comorbidities, and have an impact not only on physical health and increased hospital length
      of stay, but also on a lower functional outcome, low self-esteem and poorer quality of life
      and lead to non-compliant to antipsychotics.

      In Taiwan, a large scale survey on 650 patients with schizophrenia or schizoaffective
      disorder from 36 community psychiatric rehabilitation centers or hospital-affiliated day
      hospitals in Taipei area revealed an overall metabolic syndrome prevalence of 34.9%, with
      38.9% in female and 31.5% in male patients, respectively. The difference of metabolic
      syndrome prevalence between those patients and the general population was marked in male
      patients under 40 years of age and in female patients under 50. The authors suggested that
      BMI≧24 kg/m2 and age over 40 years old are two important risk factors of metabolic syndrome.
      Since the implementation of second generation antipsychotics (SGAs), especially clozapine,
      olanzapine or quetiapine, the metabolic syndrome prevalence exaggerated. Bai and her
      associates (2009) carried a large survey on 567 hospitalized of patients with schizophrenia
      under SGAs (clozapine =231, olanzapine n=94 and risperidone =242) for an average duration of
      45.8+/-27.8 months, and revealed the prevalence of metabolic syndrome among all subjects was
      23.8%. The clozapine group had a higher prevalence of metabolic syndrome (28.7%) than did the
      olanzapine (24.2%) and risperidone groups (19.5%) (P=0.039), and the clozapine group had
      lower levels of adiponectin (8.46+/-6.02 mg/mL) than did the olanzapine (10.26+/-4. 9 mg/mL)
      and risperidone groups (10.69+/-7.43 mg/mL) (P=0.001). The authors also found that
      adiponectin level was negatively correlated with BMI increase after initiation of SGAs
      treatment. Beside the increase use of SGAs, the use of mood stabilizers such as lithium or
      valproic acid in patients with bipolar disorder can also lead to body weight increment and
      metabolic syndrome.

      Introduction of green tea:

      Green tea is one of the most popular beverages in the world. It is made solely with the
      leaves of Camellia Sinensis that have undergone minimal oxidation during processing. Green
      tea is believed to have beneficial effects in prevention and treatment of many diseases, such
      as cancer-prevention and adjunct to chemotherapy for malignancy, to reduce mental and
      physical stress and improve memory function, to increase bone mineral density, and to
      decrease body weight. An epidemiological human study also showed that consumption of tea for
      more than 10 years led to a lower percentage of total body fat and smaller waist
      circumfluence. The anti-obesity effects of green tea are mainly attributed to its polyphenol
      content, in particular, epigallocatechin gallate (EGCG), which is most abundant in green tea
      and has been found to inhibit adipocyte proliferation and differentiation in in vitro
      studies.

      Green Tea Extract studies in Taiwan:

      In Taiwan, green tea extract (GTE) has been used to explore the effect on obese women by
      randomized, double-blind, placebo-controlled study design. Though the result showed that
      there was only a 0.3% reduction in body weight (0.15 kg) after 12 weeks of treatment with GTE
      in the study group, the GTE group had significant reduction in low-density lipoprotein
      (LDL)-cholesterol and triglyceride, and marked increase in the level of high-density
      lipoprotein (HDL)-cholesterol, adiponectin and ghrelin. In another study investigating
      insulin resistance type 2 diabetics patients, with no statistical difference was found in any
      measured variable between the decaffeinated GTE and placebo groups. However, there were some
      statistically significant within-group changes detected in items of reduction of waist
      circumference (WC), insulin resistance (HOMA-IR) index [fasting glucose (mmol/l) X fasting
      insulin (UI/l)/22.5], and insulin level, and a significant increase in the level of ghrelin.
      In an open label study, Tsai and his associates reported that more weight loss was found in
      the treatment group than the control (6.8 versus 2.3 kg; P <0.001) after 12-week use of green
      tea meal replacement formula product. Also, the treatment group had a greater changes in
      total cholesterol (185.2 versus 215.2 mg/dl; P=0.011) and low-density lipoprotein cholesterol
      (106.7 versus 127.6 mg/dl; P<0.005). Among completers only, the treatment group again lost
      more weight (6.8 kg; n=54 versus 0.8 kg; n=56; P =0.001) and had a greater reduced total body
      fat mass (7.6%; n=37 versus 0.5%; P=0.005). The authors concluded that green tea meal
      replacement formula contributes to the lower body weight and reduced low-density lipoprotein
      cholesterol level. Wu and his colleagues have carried out a cross-sectional survey of 1,210
      epidemiologically sampled adults (569 men and 641 women) and found that habitual tea drinkers
      for more than 10 years showed a 19.6% reduction in body fat percentage (BF%) and a 2.1%
      reduction in waist-to-hip ratio (WPR) compared with non-habitual tea drinkers. The multiple
      stepwise regression models revealed that men, older age, higher BMI, and current smokers were
      positive factors for BF% and WHR. In contrast, longer duration of habitual tea consumption
      and higher total physical activity were negative factors for BF%. Longer duration of habitual
      tea consumption, higher socioeconomic status, and premenopausal status were negative factors
      for WHR.

      Previous Study of GTE in Psychiatric patients:

      Though there were a lot of researches regarding the use of GTE to treat metabolic syndrome or
      to decrease body weight across many countries, no one was focusing on the psychiatric
      patients. Katzman and his associates published a paper reporting 4 patients with resistant
      mood and anxiety disorder taking quetiapine and antidepressants, and used GTE by themselves
      for overweight and found that each patient had an unexpected decrease in total body fat mass,
      body fat percentage, and increase in lean body mass. Since weight gain is a common and
      undesirable side effect with psychiatric medications, especially the SGAs, the authors
      suggested the need for conducting controlled clinical trial using these agents to ameliorate
      these unwanted consequences.

      In this clinical trial, the investigator will use decaffeinated green tea extract to treat
      overweight patients with schizophrenia or bipolar disorder in a double-blind,
      placebo-controlled study design.
    

Intervention name(s): Green tea extract; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Green tea extract 500 mg tid for 16 weeks; Placebo tid for 16 weeks
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: double blind placebo-controlled trial
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment