Effectiveness of Nigella Sativa (Kalonji) Seed in Dyslipidemia
Condition: Hypercholesterolemia; Hypertension; Diabetes Mellitus; Metabolic Syndrome X
MeSH terms: Metabolic Syndrome; Hypercholesterolemia; Dyslipidemias
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a pilot study.

      The aim of the investigators' study is to evaluate the effectiveness of nigella sativa seed
      in the treatment of dyslipidemia.

      Dyslipidemia is a common risk factor for cardiovascular disease, the leading cause for
      morbidity and mortality among patients.

      Nigella sativa is an easily available and acceptable remedy to treat dyslipidemia and at a
      low cost.

      It is expected that by scientifically determining the effectiveness of this intervention it
      will lead to its widespread use.

      This will provide a low cost alternative to treat dyslipidemia.
    

Detailed description: 
      -  Pakistan is a developing country with limited resources and a high prevalence of
           dyslipidemia.

        -  Nigella sativa is a small plant originating in the Middle East and is found abundantly,
           growing wild in Egypt, Asiatic Turkey and the Balkan States.

        -  The seed extracts from this plant are used by herbalists in the treatment of several
           medical disorders including dyslipidemia.

      OBJECTIVE:

      To determine the effectiveness of the nigella sativa seed in the control of dyslipidemia in
      adults. This is a pilot study.

      METHODOLOGY

      DESIGN

      Double blind, randomized, controlled trial

      Inclusion Criteria:

        -  Adult (18 years or older) men and women who have serum cholesterol > 180 mgs/ dls

        -  Who consent to participate

      Exclusion Criteria:

        -  Patients with known Diabetes Mellitus

      Primary Endpoint

      The primary end point for the trial is serum LDL cholesterol concentration measured at six
      weeks after intervention.

      Secondary Endpoint

        -  Serum total cholesterol concentrations measured at six weeks after intervention

        -  Serum concentrations of HDL cholesterol measured at six weeks after intervention

        -  Serum concentrations of Triglyceride measured at six weeks after intervention

        -  Serum concentrations of Blood sugar measured at six weeks after intervention

        -  Changes in Serum Transminase and Serum Creatinine with six weeks of intervention

      Intervention Group Recommended

        -  Dietary changes

        -  Lifestyle changes

        -  Nigella sativa seed as intervention.

      Intervention details:

        -  Quantity: Two capsules of crushed nigella sativa seeds 500 mgs each

        -  Frequency: Twice daily

        -  Timing: After meals

        -  Duration: Six weeks

      Control Group Recommended

        -  Dietary changes

        -  Lifestyle changes

        -  Capsules containing Calcium Lactate

      Dietary Advice

      Study subjects will receive advice from the Principal Investigator (PI)

        -  Eat low fat, low cholesterol foods

        -  Cut down on high fat food (fatty meats and bakery goods)

        -  Use low fat cooking methods (Use nonstick pans, barbecue, roast, boil)

        -  Avoid alcohol consumption

        -  Eat more fruits, vegetables and whole grains

        -  Subjects of both groups will be given standard low cholesterol diet sheet as well

      Exercise

      Subjects in both groups will be advised to take a brisk 30 minute walk for 5 days in a week
      on empty stomach or one hour after having a meal.

      LABORATORY INVESTIGATIONS

      For lab investigations venous blood specimens will be collected for the following tests. The
      tests will be performed on 12 hour fasting samples to assess the primary and secondary
      outcomes.

        -  Total Cholesterol

        -  Low Density Lipoprotein (LDL)

        -  High Density Lipoprotein (HDL)

      Other investigations

        -  Triglycerides

        -  Fasting blood glucose (FBS)

        -  Creatinine SGPT (ALT)

      IDENTIFICATION OF STUDY SUBJECTS

      Study subjects will be identified from executive and family medicine clinics within AKUH.
      Individuals fulfilling the inclusion criteria will be informed about the study and asked to
      participate.

      INFORMED CONSENT

        -  The participants will be informed of all possible expected benefits and possible harm
           ensuing from the study

        -  Written informed consent will be obtained from the study subjects addressing the ethical
           concerns of the relevant authority

      RANDOMIZATION

        -  A randomized controlled design will be used for this trial

        -  Randomization will be done to give an equal chance to eligible subjects of being
           assigned to either group.

        -  A randomization plan with a block size of four will be used to assign subjects to the
           intervention and control groups

        -  This will be done in order to achieve an equal number of participants in both the groups

        -  A Co-Investigator will create subject identification numbers and assign group according
           to randomization.

      FOLLOW-UP & DATA COLLECTION

        -  Baseline data including information on height, weight, blood pressure, blood sugar
           fasting, serum cholesterol, HDL, LDL, triglycerides and serum creatinine will be
           collected prior to starting intervention

        -  Subjects in both study groups will be telephoned, at an interval of 10 days by the study
           assistant to ensure patient compliance

        -  At the end of six weeks period, a fasting blood sample will be taken from the study
           subjects for measuring total cholesterol, LDL and HDL concentrations, serum
           triglycerides, blood sugar fasting and serum creatinine.

        -  A food diary combining groups of foods with similar nutrient content and dietary use
           will be given to study subjects

        -  Participants will record daily food intake initially and at the end of the trial period

        -  Patients' Body Mass Index (BMI), waist hip ratio and blood pressure will be recorded at
           baseline and at the end of the study.

      ETHICAL ISSUES:

        -  Subjects in both groups of the study will be given standard dietary advice, which is
           recommended by National Cholesterol Education Program (NCEP) in cases fitting the
           inclusion criteria of this proposed study.

        -  In studies conducted previously, the nigella sativa seed has shown to demonstrate
           protective effects against nephrotoxicity and hepatotoxicity induced by either disease
           or chemicals.

        -  However, in case adverse events are observed, the intervention with nigella sativa will
           be stopped for that particular individual.

      SAMPLE SIZE CONSIDERATIONS

      This is a pilot study and will include 80 patients. Half will get N. Sativa seed capsules and
      the rest will get calcium lactate placebo capsules.

      Analysis

        -  In descriptive statistics, comparison of the two treatment groups would be done on
           variables such as age and gender. The results will be mentioned in frequency and
           percentages.

        -  In univariate analysis t-test will be applied to detect a significant difference in the
           primary outcome between the two groups.

        -  For multivariate analysis, linear regression analysis will be used to identify variables
           associated with the primary outcome (LDL concentration), and to control for confounding
           factors. A similar process will be adopted for secondary outcome variables i.e., serum
           total cholesterol concentrations and HDL.

      SITE

      Aga Khan University Hospital (AKUH), Karachi
    

Intervention name(s): Nigella sativa seed
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Dyslipidaemia; Herbal medicine; Home remedy; Alternative medicine; Metabolic syndrome