Cardiac Function Clinical Trial
Official title:
Kisel-10- a Prospective Randomized Double-blind Placebo Controlled Study of the Results of Intervention With Selenium and Coenzyme Q10 Combined, Regarding Effect With Emphasis on Cardiovascular Mortality and Morbidity.
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.
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
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention
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