Effect of Apple Polyphenols on Vascular Oxidative Stress and Endothelium Function Study (APP trial_2016)
Condition: Endothelial Dysfunction
Study type: Interventional

Summary: 
      Apple polyphenols are mostly acknowledged for their hypoglycaemic properties, but represent
      an apple active fraction with many pharmacological functions. The study aim was to examine
      their effect on uricemia and endothelial function in a sample of overweight subjects. This
      was a two-phases study. The in vitro experiment aimed to evaluate the apple polyphenols'
      ability to lower uric acid in comparison with allopurinol. The in vivo study consisted in a
      randomized, double-blind, parallel placebo-controlled clinical trial involving 62 overweight
      volunteers with suboptimal values of fasting plasma glucose (100 mg/dL≤FPG≤125 mg/dL),
      randomized to be treated with 300 mg apple polyphenols or placebo for 8 weeks.
    

Detailed description: 
      The study included a 2-week run-in period of diet standardization and an 8-week treatment
      period. At enrolment, patients were given standard behavioural and qualitative dietary
      suggestions to correct their unhealthy habits. In particular, subjects were strongly
      recommended to follow the general indications of a Mediterranean diet, avoiding an excessive
      intake of diary and red meat derived products and reducing the dietary excesses, in order to
      maintain an overall balanced diet for the entire duration of the study. Individuals were also
      encouraged to increase their physical activity by walking briskly or cycling from 3 to 5
      times for week, at least 20 minutes every time.

      The study fully complied with the ethical guidelines of the Declaration of Helsinki. The
      study protocol was approved by the Ethical Committee of the University of Bologna. All
      patients signed a written informed consent to participate.

      After 2 weeks of diet standardization, the enrolled subjects were allocated to the treatment
      with an indistinguishable pill of placebo or an active product, containing 300 mg of apple
      extract (Malus Domestica) with glycosilated polyphenols (≥90%) including glycosilated
      phloritzin (15-30%), chlorogenic acid (10-25%) and quercetin (15-25%) (kindly provided by
      Amitalia Srl, Solara, MI, Italy). Patients were asked to take the pills regularly, every day
      early in the morning. The amount of glycosilated polyphenols was assessed
      spectophotometrically at 280 nm, using synthetic catechin as standard. Glycosilated
      phloritzin, chlorogenic acid and quercetin were measured by HPCL-MS [high performance liquid
      chromatography-mass spectrometry].

      The randomization was performed 1:1 ratio and the blocks were stratified by sex and age. An
      alphabetical code was assigned to each lot code (corresponding to treatment or placebo)
      impressed on the dose box. The study staffs and the investigators, as well as all of the
      volunteers, were blinded to the group assignment. Codes were kept in a sealed envelope, which
      was not opened until the end of the trial. Dose boxes were mixed and a blinded dose box was
      assigned to each enrolled patient.

      Patients were evaluated anamnestically and by the execution of a physical examination and
      laboratory analyses at the baseline, in the middle and at the end of the trial.

      The hemodynamic variables recorded (endothelial function, arterial stiffness and related
      parameters) were investigated before and after the intervention period. All the instrumental
      measurements were carried out following standardized protocols by specially trained staff.
    

Intervention name(s): Apple polyphenols; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): 1 tablet per day at evening before sleeping; 1 tablet per day at evening before sleeping
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment