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Trial registered on ANZCTR


Registration number
ACTRN12619000102178
Ethics application status
Approved
Date submitted
18/01/2019
Date registered
24/01/2019
Date last updated
12/06/2019
Date data sharing statement initially provided
24/01/2019
Date results information initially provided
24/01/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Dietary intervention with octacosanol & vitamin K2 supplement on lipid profile, oxidative stress and inflammation in patients on atorvastatin therapy
Scientific title
Effect of octacosanol and vitamin K2 supplementation on PCSK9, lipid profile, oxidative stress and inflammation in patients on atorvastatin treatment
Secondary ID [1] 297138 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
hypercholesterolemia 311171 0
mixed dyslipidemia 311172 0
Condition category
Condition code
Cardiovascular 309790 309790 0 0
Coronary heart disease
Cardiovascular 309791 309791 0 0
Hypertension
Metabolic and Endocrine 309792 309792 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study was focused on the influence of octacosanol supplementation on proprotein convertase subtilisin kexin type 9 (PCSK9) level and lipid profile in patients on chronic atorvastatin therapy. The subjects were randomly assigned to receive either dietary supplement which consists of octacosanol (20 mg) and vitamin K2 (45 µg) (AbelaPharm, Belgrade, Serbia) or placebo. Participants used 1 capsule, either dietary supplement (octacosanol + vitamin K2) or placebo, daily with an evening meal. The subjects visited the research center three times during the study: at baseline, after 8 and 13 weeks. The diet was monitored by 3-day food record kept at baseline and at the end of the study. At each study visit, the participants underwent physician and clinical examination, as well as all anthropometric measurements. A questionnaire assessing smoking status, alcohol consumption and intake of medications was also filled out. Physical and clinical examination, vital signs, laboratory parameters (alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), creatine phosphokinase (CK) and fasting glucose) were evaluated for safety assessment. Participants had to bring all used empty and unused study supplements. At each visit any unusual or adverse effect was reported in the appropriate record forms.
Intervention code [1] 313404 0
Prevention
Intervention code [2] 313405 0
Treatment: Other
Comparator / control treatment
Placebo: magnesium stearate, microcrystalline cellulose and colloidal silicon dioxide
Control group
Placebo

Outcomes
Primary outcome [1] 318749 0
serum PCSK9 level ( ELISA method recognizes free and LDL-R bound PCSK9 in the same time, this is composite primary outcome)
Timepoint [1] 318749 0
Baseline (visit 1), at 8 weeks (visit 2) and 13 weeks (visit 3, endpoint)
Secondary outcome [1] 365916 0
serum total cholesterol (TC)
Timepoint [1] 365916 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [2] 366022 0
serum triglyceride (TG)
Timepoint [2] 366022 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [3] 366023 0
serum high density lipoprotein (HDL)
Timepoint [3] 366023 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [4] 366024 0
serum low density lipoprotein (LDL)
Timepoint [4] 366024 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [5] 366025 0
serum apolipoprotein A1 (ApoA1)
Timepoint [5] 366025 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [6] 366026 0
serum apolipoprotein B100 (ApoB100)
Timepoint [6] 366026 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [7] 366027 0
serum total antioxidant status (TAS)
Timepoint [7] 366027 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [8] 366028 0
serum total oxidant status (TOS)
Timepoint [8] 366028 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [9] 366029 0
serum advanced oxidation protein products (AOPP)
Timepoint [9] 366029 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [10] 366030 0
serum superoxide dismutase (SOD)
Timepoint [10] 366030 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [11] 366031 0
serum paraoxonase 1 (PON1)
Timepoint [11] 366031 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [12] 366032 0
serum interleukin [IL]-6
Timepoint [12] 366032 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [13] 366033 0
serum tumor necrosis factor-a [TNF-a]
Timepoint [13] 366033 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [14] 366034 0
serum high-sensitivity C-reactive protein [hs-CRP])
Timepoint [14] 366034 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [15] 366035 0
serum oxidized low density lipoprotein [oxLDL]
Timepoint [15] 366035 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)
Secondary outcome [16] 366036 0
serum soluble CD40 ligand (sCD40L)
Timepoint [16] 366036 0
visit 1 (baseline), visit 2 (at 8 weeks) and visit 3 (at 13 weeks)

Eligibility
Key inclusion criteria
Confirmed diagnosis of hypercholesterolemia or mixed dyslipidemia

The use of atorvastatin (20 mg/day) for minimum 4 months prior to the study entry

BMI: 18 - 35 kg/m2
Minimum age
40 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
triglycerides serum levels above 5.6 mmol/L, previous acute coronary syndrome within 1 month, serious heart failure, cerebral vascular disease, history of severe infections, known hypersensivity to any of the ingredients of the formulation, currently receiving agents with potential to interact with octacosanol, recent or chronic use of oral anticoagulant drugs and anticipated compliance problems. Significant pre-existing diseases including cancer, liver and/or renal insufficiency, psychiatric disorders, systematic inflammatory or autoimmune disease. In addition, patients with one of the following laboratory values above 3 times the upper limit of normal laboratory range: serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and creatine phosphokinase (CK) above 5 times the upper limit of normal

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 21214 0
Serbia and Montenegro
State/province [1] 21214 0
Serbia

Funding & Sponsors
Funding source category [1] 301698 0
University
Name [1] 301698 0
University of Belgrade - Faculty of Pharmacy
Address [1] 301698 0
Vojvode Stepe 450, 11221 Belgrade, Serbia
Country [1] 301698 0
Serbia and Montenegro
Primary sponsor type
Individual
Name
Ivan Stankovic
Address
University of Belgrade – Faculty of Pharmacy
Vojvode Stepe 450, 11221 Belgrade, Serbia
Country
Serbia and Montenegro
Secondary sponsor category [1] 301421 0
None
Name [1] 301421 0
Address [1] 301421 0
Country [1] 301421 0
Other collaborator category [1] 280498 0
Hospital
Name [1] 280498 0
Zvezdara University Medical Center, Belgrade
Address [1] 280498 0
Dimitrija Tucovica 161, Belgrade
Country [1] 280498 0
Serbia and Montenegro

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302417 0
Ethical Committee of Zvezdara University Medical Center, Belgrade
Ethics committee address [1] 302417 0
Dimitrija Tucovica 161, Belgrade
Ethics committee country [1] 302417 0
Serbia and Montenegro
Date submitted for ethics approval [1] 302417 0
20/10/2015
Approval date [1] 302417 0
27/10/2015
Ethics approval number [1] 302417 0

Summary
Brief summary
Efficacy of a combination of octacosanol and vitamin K2 supplementation versus placebo on PCSK9 level and lipid profile, as well as markers of oxidative stress and inflammation, in patients on chronic atorvastatin therapy. Statins which have favorable effects on blood lipids are increasing the level of PCSK9. The increase of PCSK9 can limit the positive effects of statins.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90174 0
Prof Miodrag Ostojic
Address 90174 0
1. Institute for Cardiovascular Diseases "Dedinje", Heroja Milana Tepica 1, 11040, Belgrade
2. University of Belgrade, School of Medicine, Dr Subotica 8, 11000 Belgrade
Country 90174 0
Serbia and Montenegro
Phone 90174 0
+381641161476
Fax 90174 0
Email 90174 0
mostojic2003@yahoo.com
Contact person for public queries
Name 90175 0
Mrs Milica Zrnic Ciric
Address 90175 0
University of Belgrade – Faculty of Pharmacy
Vojvode Stepe 450, 11221 Belgrade
Country 90175 0
Serbia and Montenegro
Phone 90175 0
+381642059363
Fax 90175 0
Email 90175 0
milicaz@pharmacy.bg.ac.rs
Contact person for scientific queries
Name 90176 0
Mrs Milica Zrnic Ciric
Address 90176 0
University of Belgrade – Faculty of Pharmacy
Vojvode Stepe 450, 11221 Belgrade
Country 90176 0
Serbia and Montenegro
Phone 90176 0
+381642059363
Fax 90176 0
Email 90176 0
milicaz@pharmacy.bg.ac.rs

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Clinical study report
Ethical approval
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary