Clinical trial NCT01524159: Bromelain and Cardiovascular Risk Factors in Diabetes
Official title: Bromelain and Cardiovascular Risk Factors in Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Disease.
Keywords: cardiovascular disease
Lead sponsor: Hebei Yiling Hospital
Sponsor class: OTHER
Collaborators: name: London South Bank University
First posted: 2012-02-01
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to evaluate the effect of dietary supplementation of bromelain (a proteolytic enzyme from the pineapple plant) on the reduction of plasma fibrinogen level among type 2 diabetic subjects who have a high risk of cardiovascular disease.

The null hypothesis \[Ho\] is: there is no significant improvement in plasma fibrinogen, serum lipid profile, blood pressure, BMI, waist circumference and C-reactive protein for subjects with type 2 diabetes who are at risk of CVD following the intervention of bromelain supplementation compared to placebo group.

The alternative hypothesis \[H1\] is: there is a significant improvement in plasma fibrinogen, serum lipid profile, blood pressure, BMI, waist circumference and C-reactive protein for subjects with type 2 diabetes who are at risk of CVD following the intervention of bromelain supplementation compared to placebo group.

Detailed description: According to American Heart Association (2010), heart disease and stroke are the No. 1 causes of death and disability among people with type 2 diabetes. At least 65% of people with diabetes die from some form of heart disease or stroke. Type 2 diabetes is associated with a two to fourfold increased incidence of ischemic cardiovascular events and markedly enhances the risk of stroke(Coutinho et al, 1999) due to a variety of associated risk factors that include high blood pressure, lipid disorders, high low-density lipoproteins (LDL) cholesterol, high triglycerides, low high-density lipoproteins (HDL) cholesterol, smoking, obesity, lack of physical activity and poorly controlled blood sugars(American Heart Association 2010).

Bromelain, a crude extract from the pineapple plant, was first introduced as a therapeutic compound in 1957 (Heinicke \& Gortner, 1957). Heinicke et al. (1971) reported that bromelain was effective for use in cardiovascular diseases as an inhibitor of blood platelet aggregation, minimizing the risk of arterial thrombosis and embolism.

A literature review identified only three human studies (in Honolulu and Germany). In view of this review and the valuable therapeutic properties of bromelain to cardiovascular disease, there is a need for a study to confirm bromelain's use for cardiovasular disease.

This study is a randomized placebo control, parallel design, and double blind, pilot efficacy study which was carried out in Hebei Yiling Hospital, China. The study assessed the effects of 12 weeks of bromelain (1050mg/day) supplementation on plasma fibrinogen level compared to usual care. Study participants were type 2 diabetes who have a risk of developing cardiovascular disease.

Eligibility criteria: Inclusion Criteria:

* Age over 18 years old
* Diagnosed type 2 diabetes (HbA1C at \>6,5%), who are at a risk of CVD indicated with the following risk parameters:

  * total cholesterol between 5.0 - 6.2 mmol/l (195.0 - 241.8 mg/dL),
  * Body Mass Index (BMI) \> 25 kg/m2
  * Waist circumference \> 101.6 cm (40 inches) for men and \> 88.9 cm (35 inches) for women
  * Triglycerides \> 1.7 mmol/L (150mg/dL)
  * HDL-cholesterol \< 1 mmol/L (40 mg/dL) for men, \< 1.3 mmol/L (50 mg/dL) for women
  * LDL-cholesterol \> 2.6 mmol/L (100 mg/dL)
  * Blood pressure \> 140/90mm Hg

Exclusion Criteria:

* Pregnant or trying to become pregnant or lactating women
* Subjects unwilling or unable to comply with study procedure
* Subjects with severe health problems including renal disease, liver disease, cardiovascular disease, and other chronic ill health conditions.
* Subjects on drug cardiovascular medication like warfarin, aspirin.
* Subjects that are taking statins.
* Subjects taking bromelain supplement and other herbal supplements known to be effective e.g. cinnamon.
* Subjects have a history of allergic reactions to bee stings, olive tree pollen or pineapple.
* Subjects have a history of occupational inhalant/skin contact with bromelain.
* Subjects have diabetes ketoacidosis recently (past 2 weeks).
* Unable to provide informed consent i.e. unable to follow diet control advice or not willing to follow study procedure.
* Subjects who is on any Chinese herbs medication

Primary outcomes:
measure: fibrinogen
timeFrame: 12 weeks
Secondary outcomes:
measure: Serum lipid profile (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides)
timeFrame: 12 weeks
measure: HbA1c
timeFrame: 12 weeks
measure: C-reactive protein
timeFrame: 12 weeks
measure: Body Mass Index
timeFrame: 12 weeks
measure: Blood pressure
timeFrame: 12 weeks
measure: Alanine transaminase
timeFrame: 12 weeks
measure: Aspartate aminotransferase
timeFrame: 12 weeks
measure: blood urea nitrogen
timeFrame: 12 weeks
measure: Creatinine
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: Hebei Yiling Hospital
state: Beijing
Study officials:
affiliation: London South Bank University
name: Ley C M, Ms
role: PRINCIPAL_INVESTIGATOR
References:
citation: American Heart Association. Prevention, Secondary. 2010. Available online at www.americanheart.org/print_presenter.jhtml [assessed 17th April 2010]
citation: Heinicke, R.M. & Gortner, W.A. 1957. Stem Bromelain - A New Protease Preparation from Pineapple Plants. Economic Botany, 11, 225-234
citation: Heinicke RM, van der Wal L, Yokoyama M. Effect of bromelain (Ananase) on human platelet aggregation. Experientia. 1972 Jul 15;28(7):844-5. doi: 10.1007/BF01923166. No abstract available.
citation: Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999 Feb;22(2):233-40. doi: 10.2337/diacare.22.2.233.