LDL-cholesterol Lowering Effect of a New Dietary Supplement
Condition: Hypercholesterolemia
MeSH terms: Hypercholesterolemia
Study type: Interventional

Summary: 
      The aim of this study was to assess the lipid-lowering activity and safety of a dietary
      supplement containing monacolin K, L-arginine, coenzyme Q10 and ascorbic acid (vitamin C).

      Twenty both gender caucasian outpatients aged 18-75 yrs with serum LDL-C between130-180
      mg/dL, not significantly modified by an appropriate dietetic regimen assumed two different
      dietary supplements (Argicolina [trade mark]: A; Normolip 5 [trade mark]: N) both containing
      monacolin K 10 mg for 8 weeks each separated by a 4-week wash-out period in a single center,
      controlled, randomized, open-label, cross-over clinical study. Exclusion criteria were
      pregnancy or breast-feeding; known liver, renal or muscle diseases; serum triglycerides (TG)
      greater than 350 mg/dL; previous cardiovascular events; concomitant neoplastic or
      immunodepressive disease; use of lipid-lowering drugs or dietary supplements within the last
      three weeks; concurrent use of thiazide diuretics, oral contraceptives containing estrogen or
      progestogen, systemic corticosteroids; use of psycho-active substances, drug or alcohol
      abuse; neurological or psychiatric diseases that could affect consent validity or impair the
      patient's adherence to the study protocol. Evaluation criteria were Tot-C, LDL-C,
      HDL-cholesterol, TG, fasting blood glucose, aspartate aminotransferase, alanine
      aminotransferase, creatinkinase, gamma-glutamyl-transpeptidase, humeral blood pressure and
      heart rate measured at the start and a the end of each treatment period. Safety was monitored
      through the study.
    

Detailed description: 
      Between July 2016 and April 2017 eligible patients were recruited among the outpatients
      attending the Obesity Center of the Endocrinology Unit 1, Cisanello Hospital, Pisa, Italy.
      Patients aged 18-75 years with serum LDL-C between130-180 mg/dL, not significantly modified
      by an appropriate dietetic regimen were considered eligible for the study. Thirty patients,
      all Caucasian, were screened. Ten were excluded during the screening process because they did
      not fulfill all the inclusion criteria (screening failure). Twenty patients were thus
      randomized, 10 to the A>N sequence and 10 to the N>A sequence.

      Study design The study was conducted in a single center according to a controlled,
      randomized, open-label, cross-over design. Each patient had to assume, in a randomized
      sequence, both treatments (A, 1 sachet/day; N, 1 capsule/day) for 8 weeks each separated by a
      4-week wash-out period. The study plan included the initial screening visit (V1), an entry
      visit at start of the first treatment period (V2), a visit at the end of the first treatment
      period (V3, 56 ±5 days after V2), a wash-out period of 4 weeks (±5 days), a visit at start of
      the second (crossed over) treatment period (V4), and a visit at the end of the second
      treatment period (V5, 56 ±5 days after V4) (Figure 1). Tot-C, LDL-C, HDL-cholesterol (HDL-C),
      TG, fasting blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      creatinkinase (CK), gamma-glutamyl-transpeptidase (GGT), humeral blood pressure and heart
      rate were measured at V1, V3, V4 and V5. Blood analyses were centrally performed in the
      laboratory of the Endocrinology Unit using standard enzymatic techniques; LDL-C was measured
      directly. Clinical safety was monitored throughout the study. If required, the patient could
      be re-evaluated at any time during the study, aside of the visits scheduled.

      Statistical Methods The minimum level of statistical significance was set to p<0.05
      two-sided, therefore 95% confidence limits (95%CIs) were calculated. All reported p-values
      and CIs are two-sided.

      The primary efficacy variable was the LDL-C change between the start and the end of each
      treatment period, expressed as a percentage of the initial value. Therefore, mean and 95%CIs
      of changes within treatment periods (from V2 to V3 and from V4 to V5) for the experimental
      and the control treatment, irrespective of sequence, were calculated. The main analysis was
      the determination of the two-sided 95%CI of the between-treatment mean difference in the
      primary variable. Setting 0.10 (i.e. 10% of the initial value) as the minimum clinically
      relevant difference, the two treatments were considered equivalent if the two-sided 95%CI of
      the difference in their LDL-C change from baseline was entirely between -0.10 and +0.10.
      Parallel calculations were carried out on absolute, rather than relative to baseline, LDL-C
      changes. Tot-C and HDL-C were analysed as described above for LDL-C; for TG levels (which
      were approximately log-normally distributed) analogous calculations were performed on
      logarithmic transformations and changes were expressed as ratios. Between-treatment
      comparisons were expressed as A-N differences for cholesterol values and as A/N ratios for TG
      values. The effects on LDL-C were additionally tested in sensitivity multivariate analyses:
      split-plot analysis of variance for cross-over studies on final-baseline changes, and
      analysis of covariance on the difference between the final values adjusted for sequence and
      for the difference between the baseline values. Efficacy analyses had to be performed in the
      intention-to-treat population, i.e. all patients with at least one post-baseline control). A
      sensitivity analysis of the primary variable was also planned in the per-protocol population,
      i.e. all patients without major protocol violations. Safety results had to be reported in all
      patients who had assumed at least one dose of one study drug. Statistical analyses were
      performed by the Studio Associato Airoldi Cicogna and Ghirri, Milan, using the SAS Software
      version 9.4 (SAS Inc, Cary, NC).

      Sample Size The sample size was calculated for the main efficacy analysis described above,
      i.e. the determination of the two-sided 95% CI of the between-treatment mean difference in
      the LDL-C change from baseline. Assuming a standard deviation (SD) of the difference no
      greater than 0.12, based on a previous cross-over study for the difference between monacolin
      K and placebo [11], it was estimated that 18 patients were required to prove the equivalence
      with a power of 0.80. This figure was rounded to 20 enrolled patients allowing for possible
      exclusions from the analysis.
    

Intervention name(s): Argicolina; Normolip
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 8 weeks; 8 weeks
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment