Role of a Combination of Nutraceuticals (Ritmonutra) on Benign Supraventricular and Ventricular Arrhythmias
Condition: Ventricular and Atrial Extrasytoles
MeSH terms: Arrhythmias, Cardiac
Study type: Interventional
Phase: Phase 4

Summary: 
      Study on the role of a combination of nutraceuticals (Ritmonutra) with an effect on benign
      supraventricular and ventricular extrasystoles in subjects free of a specific organic heart
      disease. It has been suggested treatment with a nutritional supplement, able to normalize the
      'cardiac electrophysiology' and help to maintain wellness. Ritmonutra ® is a combination of
      nutraceuticals®, including Omega-3 polyunsaturated fatty acids, Hawthorn, Astaxanthin and
      Vitamin E, help to normalize the heart pacing, reducing the total number of benign
      extrasystoles and consequently improving the quality of life.
    

Detailed description: 
      Benign supraventricular and ventricular extrasystoles may frequently occur in subjects free
      of a specific organic heart disease. use of potent anti-arrhythmic is not indicated for these
      kind of arrhythmias but the occurrence of this type of extrasystoles may generate concern in
      patients and consequently worse quality of life.

        1. Study Rationale Supraventricular and ventricular extrasystoles may frequently occur in
           subjects free of a specific organic heart disease. The prognosis of these arrhythmias is
           benign and the only clinical indication is to perform periodic medical examinations to
           confirm the absence of an organic heart disease during follow up. Treatment of these
           benign arrhythmias doesn't required use of potent anti-arrhythmic drugs because of their
           potential side effects. However, the occurrence of this type of extrasystoles may
           generate concern in patients despite the assurances of the physician, and consequently
           worse quality of life. For these reasons it has been suggested treatment with a
           nutritional supplement, able to normalize the 'cardiac electrophysiology' and help to
           maintain wellness . Ritmonutra ® is a combination of nutraceuticals with a demonstrated
           efficacy on preserving the physiological cardiovascular functions in addition to an
           adequate diet. Ritmonutra ® is classified by the Ministry of Health as a food supplement
           with Notification in 26 Settmbre 2011. The functional components of Ritmonutra ®,
           including Omega-3 polyunsaturated fatty acids, Hawthorn, Astaxanthin and Vitamin E, help
           to normalize the pace, reducing the total number of benign extrasystoles, and
           consequently improving the quality of life. According to preliminary studies performed
           in patients with benign extrasystoles, both supraventricular and ventricular, free of
           specific heart disease, Ritmonutra ® has been demonstrated to have a significant effect
           in reducing the number of total extrasystoles and in improving the wellness of the
           subject. In particular, Ritmonutra ® was shown to improve the social life of individuals
           and reduce the limitations caused by emotional state, without side effects.

        2. AIM OF THE STUDY

           Aim of the study is to investigate whether addition of Ritmonutra in addition to a
           adequate diet can improve and normalize the regular rhythm in patients free of specific
           organic cardiovascular disease compared to a mere placebo. Moreover, in patients with
           symptomatic benign extrasytoles, the investigators want to evaluate whether this
           nutraceutical supplement can reduce the discomfort related to perceiving these
           arrhythmias and consequently improve life quality.

        3. STUDY DESIGN multicentre, randomized, controlled parallel-group study.

        4. STUDY POPULATION The study will include participation of one clinic centre coordinating
           150 general practitioners (GPs). Each GP will select at least 10 subjects of both
           gender, All participants will give written informed consent to the protocol approved by
           the local institutional review boards. At least 150 doctors will take part in the study;
           each will treat at least 10 subjects of both genders with diagnosis of symptomatic
           benign ventricular and supraventricular extrasytoles, free of specific organic
           cardiovascular disease and not requiring pharmacological therapy.

           Indicators:

           GPs are required: 1) to record a full medical history, including smoking and drinking
           habits, based on a pre-defined clinical record; 2) to collect demographic and
           anthropometric measures (height, weight, waist circumference at the iliac crest); 3) to
           perform a complete physical exam. At the first visit and after 4 and 8 weeks all
           eligible patients will perform a complete physical exam that includes measure of office
           blood pressure and heart rate in the sitting position and in triplicate, using a manual
           sphygmomanometer, according to international guidelines. Measurements will be rounded to
           the closest 2 mmHg interval. The baseline visit and the others screening visits also
           include Electrocardiogram (ECG), Ergometric test, Echocardiogram and Holter ECG.

           The primary endpoint is reduction of total number of extrasystoles. Secondary endpoint:
           the improvement in the wellness of the subject and consequently in the life quality.

           4.1. Sample size The estimate of the sample size was performed by the SISA method
           (Simple Interactive Statistical Analysis) - Machin, David and Campbell, Michael J.
           (1987) Statistical Tables for the Design of Clinical Trials. Blackwell Scientific
           Publications, Boston. Based on the values of a previous preliminary study comparing
           Ritmonutra ® with a control group (-58.5% reduction of total extrasystoles after 4 weeks
           with Ritmonutra ® compared with-0.5% in the control group) an approximate estimate was
           made of the number of observations necessary so that the two percentages are significant
           at the 5% probability level: 12 subjects cases in each group.

        5. TREATMENTS

           All subjects will receive dietary counseling determined by the general practitioner
           depending on the subject's clinical condition, in accordance with the instructions of
           the Coordinating Site. Centralized randomization will be used to assign subjects to one
           of the two study treatments, Inert Placebo - Vitamin B complex + diet or vitamin B
           complex - Ritmonutra ® + diet. How Ritmonutra will be taken: 2 tavgel gum daily of
           Ritmonutra ® or vitamin B complex 2 tablets chewing a day.

           Duration of treatment: Subjects in both groups will take the assigned treatment for 4
           weeks. Ritmonutra ® contains: 720 mg of Fish Oil with Omega-3, including 480 mg of EPA
           and 40 mg of DHA, Hawthorn (extract from Crataegus mongyna) 300 mg equivalent to 5.4 mg
           of vitexin, 4 mg of Astaxanthin and 36 mg of Vitamin E.

        6. EVALUATION CRITERIA At baseline, and after 4 and 8 weeks cardiovascular parameters
           (blood pressure, heart rate, Holter ECG) and the SF-36 quality of life questionnaire and
           the 4SQ_2011questionnaire investigating somatic symptoms related to stress will be
           assessed as well as the others clinical parameters necessary to evaluate the
           cardiovascular risk and changes in life quality.

        7. STUDY PROCEDURES Each doctor will initially be given a login and password allowing
           confidential and individual access to the website www.ritmonutra.net for data entry. In
           order to avoid sampling errors, the doctor will include in the study the first 10
           consecutive subjects who meet the admission criteria (see point 4). The doctor will
           complete the appropriate form (also available on the ritmonutra.net site) insert
           information of the point 0 and will assign the subject to one of two regimens, Inert
           Placebo - Vitamin B complex + diet or vitamin B complex - Ritmonutra ® + diet, based on
           what has been determined by centralized randomization under the responsibility of Prof.
           Bruno Trimarco and delivery to the subject the treatment required for 4 weeks
           (Ritmonutra ® or control). After four weeks all the subjects under go to Holter ECG, the
           SF-36 and 4SQ_2011. After the first four weeks patients will receive the alternative
           treatment provided by randomization (control - Ritmonutra ®). After another four weeks
           all the subjects underwent 24-Hour Holter (ECG) monitoring , the SF-36 and 4SQ_2011.

        8. STATISTICAL ANALYSIS The statistical analysis of baseline homogeneity will be undertaken
           using the chi-square test and analysis of variance, if appropriate.

           The statistical analysis to assess the clinical efficacy will be based on a comparison
           between differences at the various time points versus the baseline obtained in the two
           treatment groups and will be conducted using the chi-square test and analysis of
           variance, where appropriate.

           The level of significance will be considered to be an Alfa = 0.05 (type I error) and the
           power level a beta = 0.90 (type II error).

        9. STUDY TIMELINES The study will start from the time the login and password have been
           delivered.

       10. AVAILABILITY OF DATA All participants will be informed of the results once the data have
           been processed.

       11. COORDINATING COMMITTEE

      For any clarification on the study contact:

      Dr. Claudio Benvenuti - Medical Management Rottapharm | Madaus Valosa via di Sopra, 9-20900
      Monza tel 039 7390406 - Fax 039 7390393 email: @ claudio.benvenuti rottapharm.com.
    

Intervention name(s): Ritmonutra; placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Ritmonutra ® contains: 720 mg of Fish Oil with Omega-3, including 480 mg of EPA and 40 mg of DHA, Hawthorn (extract from Crataegus mongyna) 300 mg equivalent to 5.4 mg of vitexin, 4 mg of Astaxanthin and 36 mg of Vitamin E
Other intervention name(s): Omega-3 polyunsaturated fatty acids; Hawthorn; Astaxanthin; Vitamin E; Vitamin B complex; Diet
Intervention MeSH terms: Vitamins; Vitamin E; Vitamin B Complex
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Arrhythmias; Life quality