Intervention With Selenium and Q10 on Cardiovascular Mortality and Cardiac Function in the Elderly Population in Sweden
Condition: Cardiovascular Mortality; Cardiac Function
Study type: Interventional

Summary: 
      The dietary supplements selenium and Q10 has been evaluated in a double blind
      placebo-controlled study in an elderly Swedish population. The hypothesis is that as a
      majority of Northern Europeans suffers insufficient levels of selenium that is used by the
      cell in the building of at least 25 different enzyme systems in the body, and that the cell
      need presence of Q10 in order to produce the selenium containing enzymes, we wanted to
      evaluate the effect of a combined intervention of the two supplements in an elderly
      population in Sweden. All participants were controlled every 6 months, and the intervention
      was 48 months in each participant. Besides blood samples, echocardiography and cardiac
      natriuretic peptides were analyzed at start, every 6 months and at end of the study.
    

Detailed description: 
      The amount of patients suffering from heart failure is increasing throughout the Western
      hemisphere. The prognosis of heart failure is poor, in many cases worse than malignant
      diseases.

      Several studies have demonstrated that by evaluating the plasma concentration of the
      natriuretic peptides that are stimulated by increased wall tension of the myocardium, it is
      possible to estimate the risk of cardiovascular mortality.

      Scientific reports have demonstrated decreased symptoms of heart failure after selenium
      supplementation. Selenium, which is acquired by the body through food, often exists in low
      levels in the body in the northern parts of Europe due to poor levels of selenium in the
      soil. Animal studies have shown that selenium has a positive effect on the myocardium.

      Ubiquinon, commonly called Q10, has a central position in many of the enzyme systems of the
      body. It has recently been shown that the body requires the presence of Q10 to produce
      selenium containing enzymes which are central in the energy handling processes of cells.

      The aim of the present study is to evaluate whether the supplementation of selenium combined
      with Q10 can influence heart failure and cardiovascular mortality in an elderly population.

      In 1998 all people aged between 70-80 years living in the Kinda municipality in Sweden were
      offered the chance to participate in an epidemiological study with an emphasis on heart
      failure. Of the 1130 people living in the municipality in the specified age group, 871 agreed
      to participate in the study. Participants have been questioned regarding a new patient
      record, examined, new echocardiograms have been performed, blood samples drawn and health
      related quality of life evaluated. These participants will also be offered the chance to
      participate in a follow-up of this epidemiological study. In addition to this, they will be
      offered the chance to participate in the present intervention study where they will be given
      a dietary supplement of 200 microgram selenium/day and 200 milligram Q10/day, or a placebo.

      No serious side effects from these supplements have been observed in earlier studies using
      the doses planned in this intervention study. The dietary supplements are sold without any
      restrictions as over the counter products.

      During the study all participants will be followed-up with blood samples, a new patient
      record, and new tablets every six months. Evaluation of health related quality of life will
      be performed at inclusion, after 18 months and after 48 months. The quality of life will be
      evaluated using the validated instrument SF-36. At the end of the study, new blood samples
      and new echocardiograms will be obtained.

      Aim To evaluate changes in primarily cardiovascular mortality and all-cause mortality , and
      secondary, cardiac function as evaluated with cardiac natriuretic peptides and
      echocardiography after dietary supplementation of selenium and Q10, or a placebo, in an
      elderly population during 48 months of intervention.

      Secondary objectives To evaluate the cost-effectiveness of selenium and Q10 combined during
      an intervention of 48 months. To measure the perceived health related quality of life during
      intervention.

      Possible health related economic consequences will be evaluated using the instrument EQ-5D.

      Endpoint Development of cardiovascular disease, worsening of existing cardiovascular disease,
      and cardiovascular mortality during intervention with selenium and Q10 in comparison with
      placebo.

      Change of concentration of natriuretic peptides during intervention with selenium and Q10.

      Secondary endpoint Development of all-cause mortality during intervention with selenium and
      Q10. Consumption of hospital resources during intervention with selenium and Q10 in relation
      to placebo.

      Study design A prospective randomized double-blind placebo controlled study. Randomising The
      randomising procedure will be performed using PharmaNord's computer assisted randomization in
      blocks of 6.

      Study All participants will be offered a selenium-containing yeast preparation corresponding
      to 200 micrograms of selenium/day, and ubiquinone corresponding to 200 milligrams/day, or a
      placebo.

      During the intervention period, blood samples will be drawn every six months from all
      participants, and the following list of substances are to be analyzed:

        1. NT-proBNP

        2. Thioredoxin

        3. Thioredoxinreductase

        4. Lipidperoxidase

        5. Panel of cytokines

        6. "New" biomarkers for heart failure. All blood sample results will be blinded for both
           the investigators and the participants.

      Inclusion criteria Individuals living in the municipality of Kinda, aged between 70-80 years
      who have accepted participation in the study, and who are expected to fulfill a study period
      of 4 years.

      Exclusion criteria Recent myocardial infarction (within 4 weeks). Planned cardio-vascular
      operative procedure within 4 weeks. Hesitation concerning if the candidate can decide for
      him/herself whether to participate in the study or not, or if he/she understands the
      consequences of participation.

      Serious disease that substantially reduces survival or where it is not expected that the
      participant can cooperate for the full 4 year period.

      Other factors making participation unreasonable, such as long/complicated transport to the
      Primary Health Center where the project is managed, or drug/alcohol abuse.

      Preparations Coenzyme Q10 ( Bio-Quinon 200mg, PharmaNord, Vejle, Denmark) Selenium
      (SelenoPrecise 200 microgram, PharmaNord, Vejle, Denmark) Placebo (PharmaNord, Vejle,
      Denmark) All preparations will be ingested twice a day together with food.

      The preparations will be supplied by PharmaNord, Vejle, Denmark. The preparations will be
      stored in a locked, dry, dark room where only the personnel involved in the study will have
      access. A rigorous log regarding received and delivered preparations will be kept.

      Concomitant pharmacological treatment Participants who have been prescribed pharmacological
      drugs due to concomitant diseases/medical conditions are advised to continue treatment.

      Participants who have been prescribed anticoagulants containing warfarin are advised to
      continue treatment, but it is recommended that they analyze the INR at the start of the
      intervention with selenium and Q10, and again after 2 weeks. Interactions between
      selenium/Q10 and warfarin have been discussed in literature but have not been demonstrated.

      Where is the code list? The code list containing information of active treatment/placebo is
      kept in a sealed envelope at PharmaNord, Vejle, Denmark, and the codes will not be broken
      before the end of the study, or in the case of an emergency where information regarding the
      intervention is required.

      Side effects Serious side effects should be reported to both the National Board of Health and
      Welfare and PharmaNord.

      Dropouts Participants choosing to discontinue the study for any reason will be followed
      according to the intention to treat principle. All dropouts will be registered, as well as
      their reason for discontinuing participation, if the participant chooses to supply this
      information.

      Participants who take supplements of selenium or Q10 for any reason outside the study will be
      regarded as dropouts.

      Ethical permission Ethical permission shall be accepted from the Ethical Review Board before
      the start of the study. Oral and written "patient" information will be given to all
      participants, as well as a signed copy of the consent form .

      Permission from the Swedish Medical Products Agency Contact has been taken with the Medical
      Products Agency in Sweden regarding permission to use the preparations during the
      intervention. However, the principal investigator of the project has been orally informed by
      the Agency that since this was not regarded as a trial of a medication, but rather of food
      supplement commodities that are readily available as commercial goods, the Agency would not
      review the study protocol.

      Participants 500-600 healthy individuals as well as patients treated for various diseases and
      already participating in the former epidemiological heart failure study in the Kinda
      municipality.

      Basic power calculation Using the assumption that the incidence of occurrences in the placebo
      group during a follow up of 4 years is 40%, and 28% in the intervention group, i.e. a
      difference in incidence between the groups of 30% and an absolute difference of 12%, 244
      individuals are needed in order to obtain a statistical power of 80% with a significance
      level of 5%. A dropout frequency of 15% is to be expected, which is why a minimum of 560
      individuals is needed in order to obtain significant differences.

      Principal investigator Urban Alehagen, Resident, Dept of Cardiology, University Hospital of
      Linköping

      Co-investigators Ulf Dahlström, Professor, Dept of Cardiology, University Hospital of
      Linköping Anders Rosén, Professor, Dept of Cellular Biology, University of Linköping Mikael
      Björnstedt, Professor, Dept of Pathology, Karolinska University Hospital, Stockholm
    

Intervention name(s): Selenium and ubiquinon (Q10) combined
Intervention type(s): Dietary Supplement
Intervention description(s): A combination of 200 mg/day of coenzyme Q10 (Bio-Quinon 100 mg B.I.D, Pharma Nord, Vejle, Denmark) and 200 µg/day of organic selenium (SelenoPrecise 200 µg, Pharma Nord), or placebo
Other intervention name(s): Bio-Quinon 100mg; SelenoPrecise 200microgr
Intervention MeSH terms: Selenium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Selenium; Q10; dietary supplement; elderly population; intervention; All-cause mortality; cardiac function